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1.  PA02.06. Tracking the transitions in Guggulu Kalpana : An extensive review through Brihat Trayi and Laghu Trayi 
Ancient Science of Life  2013;32(Suppl 2):S51.
Purpose:
Guggulu Kalpana enjoys a coveted position in the arena of Ayurvedic therapeutics. Guggulu Kalpana is widely used in Charak Samhita & Sushruta Samhita and its notable collection is described in Ashtanga Sangraha. Out of laghu trayi, Sharangadhara Samhita has described Guggulu kalpas at length. Though its present form is closely related to Guti Vati Kalpana, it has not been the case always. Present study was attempted to track these transitions in Guggulu Kalpana during period of Brihat Trayi and Laghu Trayi and propose the importance of this journey in the view of current Ayurvedic pharmaceutics and therapeutics.
Method:
A comprehensive review of Brihat Trayi and Laghu Trayi was done. Opinions of their critics as well as contemporaries were also taken into consideration. These views were collated on the basis of current trends and researches in Guggulu Kalpana.
Result:
Amongst other categories, main usage of Guggulu Kalpana was seen in form of Kwatha and Guti Vati Kalpana. Though used in great deal, Brihat Trayi doesn’t describe Guggulu in every respect. Different point of view regarding preparation of Guggulu Kalpana was observed in all these treatises. Various functional limitations and constant improvisations seemed to have shaped the Guggulu Kalpana in its today's form.
Conclusion:
Current status of Ayurvedic pharmaceutics in general and Guggulu Kalpana in particular, is greatly influenced by Sharangadhara Samhita. It mainly shows use of Guggulu in GutiVati form. The Brihat Trayi treatises, however display its use in Conjunction of Kwatha Kalpana chiefly. This paradigm shift in the pharmaceutics of Guggulu Kalpana highlights the buoyant and pliant nature of Ayurveda. The difference in choice of kalpana is explained on the basis of soluble alkaloid content and insoluble resinous gum content of Guggulu. Thus, this study is helpful to understand the progression of Ayurvedic therapeutics and prospective avenues for its advancement.
doi:10.4103/0257-7941.123867
PMCID: PMC4147523
2.  Neutraceuticals in Ayurveda with special reference to Avaleha Kalpana 
Ancient Science of Life  2008;28(2):29-32.
The use of Neutraceuticals has drastically risen in recent years. Dr Stephan De Felice coined the term Neutraceuticals from “nutrition” and “pharmaceutical” in 1989. Related terms are “functional food” and “dietary supplement”. In Ayurvedic pharmaceutics there are some secondary preparations like Avaleha Kalpana (Medicated semisolid preparation), Asavarista Kalpana (fermented preparation), Sneha Kalpana (Medicated fatty preparation), Ksheerapaka Kalpana (Medicated milk preparation) etc. which can be correlated with Neutraceuticals. In this paper “Neutraceuticals” and “Avaleha Kalpana” have been correlated and discussed.
PMCID: PMC3336349  PMID: 22557309
Neutraceuticals; Functional food; Avaleha Kalpana
3.  A comparative pharmacological evaluation of Taila (oil) and Ghrita (ghee) prepared with Guduchi (Tinospora cordifolia) 
Ayu  2010;31(4):504-508.
Guduchi (Tinospora cordifolia wild miers) is a well-known medicinal plant, which is abundantly used in different ayurvedic formulations utilizing varieties of media. The drug has properties like Rasayana (rejuvenating property), Krimighna (anthelmintics), and Kushtghna (used in skin disorders), as described in ayurvedic literature. Taila (oil) and Ghrita (ghee) are used as media in Ayurvedic Sneha (oleaginous) formulations. Both the test drugs, Guduchi Taila and Ghrita, are prescribed in Vatrakta (gout) and also indicated for Kushtha (skin disorder). With all these details, the Guduchi Taila and Guduchi Ghrita samples, prepared by using Taila and Ghrita as media, have been subjected to comparative pharmacological investigations, to assess the impact of the media on the expression of pharmacological activity. The formulations have been evaluated for immunomodulation, anti-inflammatory, and anti-stress activities. Both the formulations have been found to be active in most of the experiments, however, with the change of media, their results vary at different levels. Taila prepared from Guduchi was found to have an immunostimulating activity. The formulation prepared with Ghrita exhibited an anti-stress effect with an immunosuppressing activity.
doi:10.4103/0974-8520.82036
PMCID: PMC3202249  PMID: 22048548
Guduchi (Tinospora cordifolia wild miers); Guduchi Taila; Guduchi Ghrita; Immunomodulation; Anti-inflammatory; Anti-stress
4.  A clinical review of different formulations of Vasa (Adhatoda vasica) on Tamaka Shwasa (asthma) 
Ayu  2010;31(4):520-524.
Vasa (Adhatoda vasica Linn.) is a well known and easily available drug in almost all the seasons. Easy availability of any drug gains popularity among physicians as well as pharmaceuticals and this is the reason why almost every Kalpana of Vasa is found described in the Ayurvedika text. The different dosage forms of Vasa like Kvatha, Avaleha, Sneha, and Sandhana have been used for the treatment of Shwasa Roga. A number of research studies have been performed on different formulations of Vasa and its effect on Shwasa Roga. Therefore, a review study has been carried out on the Vasa extract, Vasa Avaleha (prepared from Svarasa and Kvatha), Vasa Ghrita, Vasarishta, and Vasakasava on Shwasa Roga, to know which formulation is better. It was found in the review that Vasa Ghana, Vasa Ghrita (1), and Vasa Avaleha have shown good results on Tamaka Shwasa.
doi:10.4103/0974-8520.82032
PMCID: PMC3202261  PMID: 22048552
Ghana (extract); Avaleha; Shwasa; Asava; Arishta; Tamaka Shwasa; Adhatoda vasica
5.  A progressive review of Sandhana kalpana (Biomedical fermentation): An advanced innovative dosage form of Ayurveda 
Ayu  2011;32(3):408-417.
Sandhana kalpana (biomedical fermented formulations) are one of the best dosage forms of Ayurveda in practice since thousands of years. In order to prepare these medicaments, certain sets of conditions are prearranged, which lead to fermentation. Thus, products bequeath with self-generated ethyl alcohol, which potentiate these preparations (Asava–Arishta), pharmaceutically and therapeutically. Commonly, medicinal and commercial components of these formulations are prompting many researchers to contribute in manufacturing, quality control, safety, and efficacy of these formulations. To cope up with this, literature related to Asava–Arishta has been surveyed from the Vedic period to recent publications of Government of India, ie, Ayurvedic Formulary of India, and presented briefly here. In this review paper, we have discussed pioneering facts such as nature and amount of carbohydrate, type of containers, optimum temperature, variety and relevance of initiator of fermentation, manufacturing, regulatory rules, and business aspects of Asava-Arishta. After going through this basic information, any academician or researcher may show a way to further strengthen this dosage form.
doi:10.4103/0974-8520.93925
PMCID: PMC3326893  PMID: 22529661
Asava; Arishta; ethyl alcohol; fermentation; quality control; Sandhana kalpana
6.  The effect of ghee (clarified butter) on serum lipid levels and microsomal lipid peroxidation 
Ayu  2010;31(2):134-140.
Ghee, also known as clarified butter, has been utilized for thousands of years in Ayurveda as a therapeutic agent. In ancient India, ghee was the preferred cooking oil. In the last several decades, ghee has been implicated in the increased prevalence of coronary artery disease (CAD) in Asian Indians due to its content of saturated fatty acids and cholesterol and, in heated ghee, cholesterol oxidation products. Our previous research on Sprague-Dawley outbred rats, which serve as a model for the general population, showed no effect of 5 and 10% ghee-supplemented diets on serum cholesterol and triglycerides. However, in Fischer inbred rats, which serve as a model for genetic predisposition to diseases, results of our previous research showed an increase in serum total cholesterol and triglyceride levels when fed a 10% ghee-supplemented diet. In the present study, we investigated the effect of 10% dietary ghee on microsomal lipid peroxidation, as well as serum lipid levels in Fischer inbred rats to assess the effect of ghee on free radical mediated processes that are implicated in many chronic diseases including cardiovascular disease. Results showed that 10% dietary ghee fed for 4 weeks did not have any significant effect on levels of serum total cholesterol, but did increase triglyceride levels in Fischer inbred rats. Ghee at a level of 10% in the diet did not increase liver microsomal lipid peroxidation or liver microsomal lipid peroxide levels. Animal studies have demonstrated many beneficial effects of ghee, including dose-dependent decreases in serum total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides; decreased liver total cholesterol, triglycerides, and cholesterol esters; and a lower level of nonenzymatic-induced lipid peroxidation in liver homogenate. Similar results were seen with heated (oxidized) ghee which contains cholesterol oxidation products. A preliminary clinical study showed that high doses of medicated ghee decreased serum cholesterol, triglycerides, phospholipids, and cholesterol esters in psoriasis patients. A study on a rural population in India revealed a significantly lower prevalence of coronary heart disease in men who consumed higher amounts of ghee. Research on Maharishi Amrit Kalash-4 (MAK-4), an Ayurvedic herbal mixture containing ghee, showed no effect on levels of serum cholesterol, high density lipoprotein (HDL), LDL, or triglycerides in hyperlipidemic patients who ingested MAK-4 for 18 weeks. MAK-4 inhibited the oxidation of LDL in these patients. The data available in the literature do not support a conclusion of harmful effects of the moderate consumption of ghee in the general population. Factors that may be involved in the rise of CAD in Asian Indians include the increased use of vanaspati (vegetable ghee) which contains 40% trans fatty acids, psychosocial stress, insulin resistance, and altered dietary patterns. Research findings in the literature support the beneficial effects of ghee outlined in the ancient Ayurvedic texts and the therapeutic use of ghee for thousands of years in the Ayurvedic system of medicine.
doi:10.4103/0974-8520.72361
PMCID: PMC3215354  PMID: 22131700
Anhydrous milk fat; cholesterol; clarified butter; coronary artery disease; ghee; lipid peroxidation; vanaspati; vegetable ghee.
7.  STANDARDISATION OF KSHEERABALA TAILA 
Ancient Science of Life  1996;16(1):21-25.
Nowadays many drug industries are manufacturing a number of oil formulations and which are not assessable to know the specific Pakas (stage) of oil preparation. In Ayurveda five stages have been mentioned for medicated oils, these Ama, Mridu, Madhya Khara and Dadgha Paka, Medicated oils obtained by Mridu, Madhya Khara and Dadgha Paka, are considered to be of therapeutic value and are advocated for clinical usage but those obtained by Ama and Dadgha pakas are not recommended. Most of the pharmacies are marketing the oils only by name but are not mentioning the Paka. In order to standardize these pakas with scientific explanation a oil preparation called Ksheerabala taila is selected for the study.
PMCID: PMC3331133  PMID: 22556766
8.  PA03.19. Clinical study on the effect of Moorchita Tila Taila Shamana Sneha and Navaka Guggulu in Hyperlipidemia – A comparative study 
Ancient Science of Life  2013;32(Suppl 2):S88.
Purpose:
Hyperlipidemia is a disorder which is identified as a potential risk factor for multitudes of diseases like cardiovascular diseases, metabolic syndrome and even hypertension. Hyperlipidemia is term used to denote raised serum levels of cholesterol or triglycerides or both. Though, there is no precise terminology for Hyperlipidemia mentioned in the Ayurvedic classics, A detailed study of Hyperlipidemia reveals its similarity to Asthayi Medo Dhatu Vriddhi on the basis of its Pathophysiology.
Method:
For Group A Moorchita Tila Taila 15ml twice daily as Shamana Sneha with Ushna jala for 30 days. For Group B Navaka Guggulu in Tablet form 500mg, 1 tab thrice daily for 30 days.
Result:
Both the groups A and B showed reduction in serum Total Cholesterol, Triglycerides, LDL–C and VLDL–C and Group A showed slight increase in HDL levels.
Conclusion:
Shamananga snehapana can be safely carried out in patients of Hyperlipidemia. Comparing both the groups, Group A treated with Moorchita Tila Taila Shamana Sneha showed better results in reducing serum lipid values than Group B treated with Navaka Guggulu
doi:10.4103/0257-7941.123916
PMCID: PMC4147563
9.  Review of research works done on Tamra Bhasma [Incinerated Copper] at Institute for Post-Graduate Teaching and Research in Ayurveda, Jamnagar 
Ayu  2013;34(1):21-25.
The metal, Tamra though mentioned in Ayurveda with a wide range of therapeutic utilities; is attributed with Ashta Maha Dosha. Hence, one should be cautious while using Tamra Bhasma. Considering the significance of Tamra in therapeutics, many studies have been carried out at different centers of India. Aim of the present study was to compile such available research works done on Tamra in the Department of Rasa Shastra and Bhaishajya Kalpana (RS and BK), IPGT and RA, Jamnagar and provide brief information about pharmaceutical, analytical, and pharmacological studies. Total eleven studies on Tamra Bhasma, which revalidated the impact of classical guidelines, safety issues, and therapeutic utilities, were screened from PG Department of RS and BK, Institute for Post-Graduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar. All studies revealed that Tamra Bhasma is safe clinically, experimentally at Therapeutic Equivalent Dose (TED) levels as no toxic hazards were reported during the treatment period. In all aspects (pharmaceutical, pharmacological, and clinical) Somnathi Tamra Bhasma has proven to be better than Tamra Bhasma. The clinical efficacy of Tamra Bhasma has been evaluated in Shvasa, Kasa, Yakrit Pliha Vriddhi, Grahani, etc. conditions. Satisfactory responses with a decrease in the intensity of signs and symptoms were reported in all the studies. Though certain limitations were observed in these researches, the results can be considered as a lead for further well stratified studies covering larger population. No adverse effects were reported in any of these studies.
doi:10.4103/0974-8520.115440
PMCID: PMC3764875  PMID: 24049401
Bhasma; Grahani; Rasa Shastra; safety; Somanathi Tamra; Tamra toxicity
10.  A comparative study on Vamana Karma with Madanaphala and Krutavedhana in Ekakushtha (Psoriasis) 
Ayu  2011;32(4):487-493.
Vamana Karma (therapeutic emesis) is the best therapy for the elimination of vitiated Kapha Dosha. In the present clinical practice Madanaphala (Randia dumetorum) is mainly used for Vamana Karma. Apart from Madanaphala, five other drugs, and in total 355 formulations are described in Charaka Samhita; one of them is Krutavedhana (Luffa acutangula) kalpa (formulations). Krutavedhana is specially indicated in Gadha (compact) Dosha condition like Kushtha (skin diseases), Garavisha (slow poison), and so on, for Vamana Karma. The present study aimed to observe the effect on Vamana Karma and by that its effect on Ekakushtha (Psoriasis). Krutavedhana Beeja Churna (seed powder) was given with Madhu (honey) and Saindhava (rock salt) as Vamana Yoga (emetic formulation), to compare it with Madanaphala Pippali Churna (seed powder). After the Sansarjana Krama (special dietetic schedule), Panchatikta Ghrita (medicated ghee) was given as Shamana Sneha (pacifying oleation). An average dose of Krutavedhana was 5.9 g. Krutavedhana could produce a good number of Vega (bouts), Pittanta Lakshana (bile coming out at the end of Vamana), and Pravara Shuddhi (maximum cleansing) in a majority of patients. Madanaphala is the best among all Vamaka (emetic) drugs, but Krutavedhana showed a similar to higher effect on Vamana Karma in terms of Antiki, Maniki, Vaigiki, and Laingiki Shuddhi (cleansing criteria). Vamana Karma by Krutavedhana showed better relief in Matsyashakalopamam (silvery scale), Kandu (itching), and Rukshataa (dryness), while Madanapahala showed better relief in Krishnaruna Varna (erythema). After completion of the Shamana (pacifying) treatment, both the groups showed nearly the same effect on Asvedanam (lack of perspiration), Matsyashakalopamam, Kandu, Rukshataa, Krishnaruna Varna, and Mahaavaastu (bigger lesion).
doi:10.4103/0974-8520.96121
PMCID: PMC3361923  PMID: 22661842
Ekakushtha; Krutavedhana; Madanaphala; Panchatikta Ghrita; Psoriasis; Vamana Karma
11.  Pharmaceutical preparation of Saubhagya Shunthi Churna: A herbal remedy for puerperal women 
Background:
In the last few decades, there has been exponential growth in the field of herbal remedies. Pharmacopoeial preparations like avleha or paka (semi-solid), swarasa (expressed juice), kalka (mass), him (cold infusion) and phanta (hot infusion), kwatha (decoction) and churna (powder) form the backbone of Ayurvedic formulations. Newer guidelines for standardization, manufacture, and quality control, and scientifically rigorous research will be necessary for traditional treatments. This traditional knowledge can serve as powerful search engine that will greatly facilitate drug discovery.
Purpose:
The aim of the present study is to standardize Saubhagya Shunthi Paka in churna (powder) form. The powder form makes this traditional drug more stable for long-term storage and hence, easier to preserve.
Materials and Methods:
Saubhagya Shunthi Paka is an ayurvedic formulation containing Shunthi (Zingiber officinalis) as one of its chief ingredients. The basic preparation of this drug is a semisolid. We checked the microbial load and nutrient values (using International Standard IS and Association of Official Analytical chemists AOAC methods)
Results:
The powdered form of Saubhagya Shunthi Churna yielded a weight loss of approximately 17.64% of the total weight of ingredients. The total energy of Churna (calculated based on nutrient content) was found higher over Paka.
Conclusion:
Saubhagya Shunthi Churna may be a good therapeutic and dietary medicine for Indian women, which may be easily prepared at home.
doi:10.4103/0974-7788.59940
PMCID: PMC2876929  PMID: 20532094
Ayurveda; Churna (powder); saubhagya shunthi paka; paka (semi-solid); puerperium
12.  Bhaishajya Kalpanaa - The Ayurvedic Pharmaceutics - An Overview 
In Ayurvedic therapeutics, drug therapy is given prime importance. There is a very well developed sub-discipline entirely devoted to drug formulations known as “Bhaisajya Kalpanaa”. Considering its importance, different aspects of this discipline have been presented in this review to familiarize the readers, especially those who have just started studying Ayurveda, with concept of ayurvedic pharmaceutics. The Ayurvedic drug formulation is based on what is known as “Pancavidha Kasaaya” concept. According to this concept there are five basic forms of formulation known as 1-‘Swarasa’ the expressed juice, 2-‘Kalka’, a fine paste obtained by grinding fresh or wet grinding dried plant material 3- ‘Kwaatha’, the decoction, 4- ‘Sheeta’ or ‘Hima’, the cold water infusion and 5- ‘Faanta’, the hot water infusion. Different aspects of their preparation and use have been discussed. Further from the above basic forms, a number of other formulations are derived; a brief description of each of them has been given along with brief outlines of drug formulations meant for specific routes. The third part of the review is devoted to discussion of influence of different factors on the expression of pharmacological activity.
PMCID: PMC3025621  PMID: 21461144
Ayurvedic pharmaceutics; Bhaisajya Kalpanaa; Pancavidha Kasaaya; Ayurvedic formulations Traditional systems of medicine
13.  Quality control evaluation of Keshamasi, Keshanjana and Keshamasi eye ointment 
Ayu  2014;35(1):58-62.
Background:
Keshanjana (collyrium) is a well known Ayurvedic preparation prepared out of Keshamasi (ash prepared by scalp hairs) mixed with Goghrita (cow's ghee). This medicine is indicated for the treatment of Shushkakshipaka (dry eye syndrome) in the classical literature of Ayurveda; hence, it was under taken for standardization and clinical evaluation in an extra-mural research project from Central Council for Research in Ayurvedic Sciences, Department of AYUSH, New Delhi.
Aim:
To develop standard quality parameters for the Keshamasi, Keshanjana and Keshamasi ointment.
Materials and Methods:
Scalp hairs of male and females collected from saloons were converted to classical Masi Kalpana and mixed with cow ghee and petrolatum in the ratio of 1:5 to prepare the Keshanjana and Keshamasi ointment respectively. Standard Operation Procedure (SOP) were adopted and recorded accordingly. The raw material, furnished products and plain Goghrita were subjected for quality control parameters i.e., physico-chemical evaluation, anti-microbial study, particle size analysis, heavy metal analysis through inductive couple plasma spectroscopy with high performance thin layer liquid chromatography fingerprints.
Results:
Rancidity was negative in all the samples, indicating that the physico-chemical parameters are in acceptable range. Lead and zinc were present in most of the samples; while all samples are were free from microbial contamination.
Conclusion:
As no standards are available to compare the results of the current study, the observations cannot be compared. Thus the profile generated in the current study can be considered as standard to refer in future studies.
doi:10.4103/0974-8520.141938
PMCID: PMC4213971  PMID: 25364202
Keshamasi; Keshanjana; ointment; quality control profile
14.  Effect of Purificatory Measures Through Cow's Urine and Milk on Strychnine and Brucine Content of Kupeelu (Strychnos Nuxvomica Linn.) Seeds 
Strychnos nux vomica Linn.(Loganaceae) commonly known as Nux vomica (Kupeelu), is a poisonous plant and its seeds are used widely in Ayurvedic system of medicine since time immemorial. Ayurveda advocates that nux vomica seeds are to be administered in therapeutics only after going through certain purificatory measures (Shodhana). There are more than six media: cow's urine (Go mutra), cow's milk (Go dugdha), cow's ghee (Go ghrita), Kanji (thin gruel), castor oil (Eranda taila) and fresh ginger juice (Ardraka swarasa) etc., which have been reported in different classical texts of Ayurveda for proper processing of nux vomica seeds. In this study, an attempt has been made to purify the seeds by using three different methods as described in ancient treatise by using cow's urine and cow's milk as media alone and together. This study revealed that all the methods studied reduced the toxicity of strychnine and brucine contents in comparison to the raw seeds as determined by HPTLC. Out of these three methods maximum reduction in strychnine and brucine contents was found when the seeds were purified by keeping them in cow's urine for seven days followed by boiling in cow's milk for three hrs.
PMCID: PMC3746529  PMID: 23983327
Kupeelu; Strychnos nuxvomica; Shodhana; strychnine; Ayurveda; brucine; Cow's milk; Cow's urine
15.  Novel Nanomicellar Formulation Approaches for Anterior and Posterior Segment Ocular Drug Delivery 
One of the most challenging areas of pharmaceutical research is ocular drug delivery. The unique anatomy and physiology of the eye impedes drug permeation to deeper ocular tissues. Nanosized carrier systems such as nanoparticles, liposomes, suspensions, dendrimers, and nanomicelles are being explored for ocular drug delivery. In this review, we have focused on application of emerging nanomicellar carrier systems in ocular drug delivery. Nanomicelles are nanosized vesicular carriers formed from amphiphilic monomer units. Surfactant and polymeric micellar nanocarriers provide an amenable means to improve drug solubilization, develop clear aqueous formulations and deliver drugs to anterior and posterior ocular tissues. Nanomicelles due to their amphiphilic nature encapsulate hydrophobic drugs and aid in drug delivery. Various methods are employed to develop nanosized micellar formulations depending upon the physicochemical properties of the drug. Nanomicellar carriers appear to be promising vehicles with potential applications in ocular drug delivery. In this review, we attempted to discuss about the progress in ocular drug delivery research using nanomicelles as carriers from the published literature and issued patents. Also, with regards to ocular static and dynamic barriers which prevent drug permeation, a brief discussion about nanomicelles, types of nanomicelles, their methods of preparation and micellar strategy to overcome ocular barriers, delivering therapeutic levels of drugs to anterior and posterior ocular tissues are discussed.
doi:10.2174/1877912311202020082
PMCID: PMC4232191  PMID: 25400717
Barriers; conjunctival/scleral pathway; drug delivery; nanotechnology; nanomicelles; patents; posterior segment; retina-choroid
16.  Dendrimeric Systems and Their Applications in Ocular Drug Delivery 
The Scientific World Journal  2013;2013:732340.
Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed.
doi:10.1155/2013/732340
PMCID: PMC3874982  PMID: 24396306
17.  Simultaneous quantification of tumor uptake for targeted and non-targeted liposomes and their encapsulated contents by ICP-MS 
Analytical chemistry  2012;84(17):7578-7582.
Liposomes are intensively being developed for biomedical applications including drug and gene delivery. However, targeted liposomal delivery in cancer treatment is a very complicated multi-step process. Unfavorable liposome biodistribution upon intravenous administration and membrane destabilization in blood circulation could result in only a very small fraction of cargo reaching the tumors. It would therefore be desirable to develop new quantitative strategies to track liposomal delivery systems to improve the therapeutic index and decrease systemic toxicity. Here, we developed a simple and non-radiative method to quantify the tumor uptake of targeted and non-targeted control liposomes as well as their encapsulated contents simultaneously. Specifically, four different chelated lanthanide metals were encapsulated or surface-conjugated onto tumor-targeted and non-targeted liposomes, respectively. The two liposome formulations were then injected into tumor-bearing mice simultaneously and their tumor delivery was determined quantitatively via inductively coupled plasma-mass spectroscopy (ICP-MS), allowing for direct comparisons. Tumor uptake of the liposomes themselves and their encapsulated contents were consistent with targeted and non-targeted liposome formulations that were injected individually.
doi:10.1021/ac301852y
PMCID: PMC3443955  PMID: 22882145
18.  TLC AS A TOOL FOR STANDARDISATION OF AYURVEDIC FORMULATIONS WITH SPECIAL REFERENCE TO KUTAJARISHTA 
Ancient Science of Life  1993;12(3-4):358-362.
In ancient days, Physicians having the comprehensive knowledge of Bhaishajya Kalpana, used to prepare the drugs themselves to treat their patients. So there was no doubt in obtaining genuine drug with desired therapeutic effect. But in recent years, the growing population and their life style, industrialization etc have forced physicians to depend on market preparations. As such we find the necessity of standardization of these preparations. The quality assessments of a drug, which is a chemical irrespective of the system is possible by ‘Thin Layer Chromatographic technique’ using known Chemical constituents as reference standards. A herbal preparation ‘Kutajarishta’, has been standardized by using this technique and the significance of the findings is discussed.
PMCID: PMC3336554  PMID: 22556614
19.  Uptake of Home-Based Voluntary HIV Testing in Sub-Saharan Africa: A Systematic Review and Meta-Analysis 
PLoS Medicine  2012;9(12):e1001351.
Kalpana Sabapathy and colleagues conduct a systematic review and meta-analysis to assess the acceptability of home-based voluntary counseling and testing for HIV in sub-Saharan Africa with some encouraging results.
Introduction
Improving access to HIV testing is a key priority in scaling up HIV treatment and prevention services. Home-based voluntary counselling and testing (HBT) as an approach to delivering wide-scale HIV testing is explored here.
Methods and Findings
We conducted a systematic review and random-effects meta-analysis of studies published between 1 January 2000 and 24 September 2012 that reported on uptake of HBT in sub-Saharan Africa, to assess the proportion of individuals accepting HBT and receiving their test result.
Our initial search yielded 1,199 articles; 114 were reviewed as full-text articles, and 19 publications involving 21 studies (n = 524,867 individuals offered HBT) were included for final review and meta-analysis. The studies came from five countries: Uganda, Malawi, Kenya, South Africa, and Zambia.
The proportion of people who accepted HBT (n = 474,377) ranged from 58.1% to 99.8%, with a pooled proportion of 83.3% (95% CI: 80.4%–86.1%). Heterogeneity was high (τ2 = 0.11). Sixteen studies reported on the number of people who received the result of HBT (n = 432,835). The proportion of individuals receiving their results out of all those offered testing ranged from 24.9% to 99.7%, with a pooled proportion of 76.7% (95% CI: 73.4%–80.0%) (τ2 = 0.12). HIV prevalence ranged from 2.9% to 36.5%. New diagnosis of HIV following HBT ranged from 40% to 79% of those testing positive. Forty-eight percent of the individuals offered testing were men, and they were just as likely to accept HBT as women (pooled odds ratio = 0.84; 95% CI: 0.56–1.26) (τ2 = 0.33). The proportion of individuals previously tested for HIV among those offered a test ranged from 5% to 66%. Studies in which <30% of individuals had been previously tested, local HIV prevalence was <10%, incentives were provided, or HBT was offered to household members of HIV-positive individuals showed higher uptake of testing. No evidence was reported of negative consequences of HBT.
Conclusions
HBT could substantially increase awareness of HIV status in previously undiagnosed individuals in sub-Saharan Africa, with over three-quarters of the studies in this review reporting >70% uptake. It could be a valuable tool for treatment and prevention efforts.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Knowledge of HIV status is crucial for both the prevention and treatment of HIV. However, according to the Joint United Nations Programme on HIV/AIDS (the UN agency responsible for HIV/AIDS), in low-and-middle-income countries only ten percent of those who need voluntary counseling and testing, because they may have been exposed to HIV infection, have access to this service. Even in health care settings in which voluntary counseling and HIV testing is routinely offered, such as to pregnant women, the number of people who use these services is low. This situation is partly because of the stigma and discrimination associated with HIV, which makes people reluctant to volunteer to come forward to be tested for HIV. To help overcome this problem, one important strategy in encouraging people to be tested for HIV is to offer them the opportunity to be counseled and tested at home—home-based voluntary counseling and testing (HBT). Using the HBT approach, people are visited in their home by health workers regardless of their perceived risk of HIV. HBT has obvious advantages and upholds the “3 Cs” principles of HIV testing: that testing is confidential, accompanied by counseling, and conducted only with informed consent.
Why Was This Study Done?
The HBT approach has received widespread international support, and the World Health Organization has recently published guidance to service providers and policy makers about the delivery of HBT. However, the acceptability of HBT, that is, whether those offered HBT actually take up the offer and are tested, remains unknown, especially in sub-Saharan Africa, the world region with the highest prevalence of HIV. So, in this study, the researchers systematically compiled all of the available studies on this topic from sub-Saharan Africa to determine the acceptability of HBT and also to and identify any factors associated with the uptake of HBT.
What Did the Researchers Do and Find?
The researchers searched several databases to identify suitable peer-reviewed studies from Africa published between January 2000 and September 2012. The researchers included studies that described any intervention to provide HIV testing at home and also reported the proportions of participants accepting HIV testing out of all individuals offered a home-based HIV test. Because different types of studies were included (such as randomized controlled trials, observational cohort studies, and cross-sectional surveys), the researchers tested the quality of included studies. Then they pooled all of the studies together to calculate the overall proportion of people who accepted HIV testing at home and the proportion who received their result.
Using these methods, the researchers included 21 studies from five African countries: Kenya, Malawi, South Africa, Uganda, and Zambia, comprising a total of 524,867 people. Overall, the proportion of people who accepted HBT ranged from 58.1% to 99.7%, with a pooled proportion of 83.3% accepting HBT (474,377 people). In the eight studies that separated data by gender, men were as likely as women to accept testing (78.5% versus 81.5%). Over three-quarters of everyone who accepted HBT received their result (77% in 16 studies reporting on this), and, importantly, the proportion of people with previously undiagnosed HIV was high (40%–79% of those diagnosed HIV-positive), emphasizing the value of HBT. The researchers also found that providing incentives, local HIV prevalence being less than 10%, and targeting HBT to household members of HIV-positive individuals may be factors associated with increased uptake of HBT, but further research is needed to verify the results of this subgroup analysis.
What Do These Findings Mean?
These findings suggest that voluntary counseling and testing for HIV at home is highly acceptable in five countries in sub-Saharan Africa, with the majority of those tested receiving their test result, highlighting the importance of this approach in the diagnosis of HIV. Therefore, by increasing uptake of testing, HBT may provide an effective tool for governments and health service providers to increase access to HIV treatment and prevention. However, testing is just the first step in the management of HIV, and this study does not address the follow-up of those who tested positive using the home-based approach, such as access to treatment, as well as repeated HBT for ongoing knowledge of HIV status. The option of self-testing was examined in only one of the studies included in this review, but the researchers identify that self-testing at home with the support HBT staff is an important area of future research. Overall, HBT has the potential to substantially increase awareness of HIV status in previously undiagnosed men and women in sub-Saharan Africa.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001351.
The World Health Organization provides extensive information on HIV testing and counseling, and the World Health Organization's guidance on home-based testing mentioned in this summary is also available
The Joint United Nations Programme on HIV/AIDS gives the latest facts and figures about the global status of HIV and about reducing stigma and discrimination around HIV
doi:10.1371/journal.pmed.1001351
PMCID: PMC3514284  PMID: 23226107
20.  Liposomes as vaccine delivery systems: a review of the recent advances 
Therapeutic Advances in Vaccines  2014;2(6):159-182.
Liposomes and liposome-derived nanovesicles such as archaeosomes and virosomes have become important carrier systems in vaccine development and the interest for liposome-based vaccines has markedly increased. A key advantage of liposomes, archaeosomes and virosomes in general, and liposome-based vaccine delivery systems in particular, is their versatility and plasticity. Liposome composition and preparation can be chosen to achieve desired features such as selection of lipid, charge, size, size distribution, entrapment and location of antigens or adjuvants. Depending on the chemical properties, water-soluble antigens (proteins, peptides, nucleic acids, carbohydrates, haptens) are entrapped within the aqueous inner space of liposomes, whereas lipophilic compounds (lipopeptides, antigens, adjuvants, linker molecules) are intercalated into the lipid bilayer and antigens or adjuvants can be attached to the liposome surface either by adsorption or stable chemical linking. Coformulations containing different types of antigens or adjuvants can be combined with the parameters mentioned to tailor liposomal vaccines for individual applications. Special emphasis is given in this review to cationic adjuvant liposome vaccine formulations. Examples of vaccines made with CAF01, an adjuvant composed of the synthetic immune-stimulating mycobacterial cordfactor glycolipid trehalose dibehenate as immunomodulator and the cationic membrane forming molecule dimethyl dioctadecylammonium are presented. Other vaccines such as cationic liposome–DNA complexes (CLDCs) and other adjuvants like muramyl dipeptide, monophosphoryl lipid A and listeriolysin O are mentioned as well. The field of liposomes and liposome-based vaccines is vast. Therefore, this review concentrates on recent and relevant studies emphasizing current reports dealing with the most studied antigens and adjuvants, and pertinent examples of vaccines. Studies on liposome-based veterinary vaccines and experimental therapeutic cancer vaccines are also summarized.
doi:10.1177/2051013614541440
PMCID: PMC4212474  PMID: 25364509
adjuvants; antigens; archaeosomes; liposomes; therapeutic cancer vaccines; vaccines; veterinary vaccines; virosomes
21.  A tumor vasculature targeted liposome delivery system for combretastatin A4: Design, characterization, and in vitro evaluation 
AAPS PharmSciTech  2006;7(2):E7-E16.
The objective of this study was to develop an efficient tumor vasculature targeted liposome delivery system for combretastatin A4, a novel antivascular agent. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, distearoyl phosphoethanolamine-polyethylene-glycol-2000 conjugate (DSPE-PEG), and DSPE-PEG-maleimide were prepared by the lipid film hydration and extrusion process. Cyclic RGD (Arg-Gly-Asp) peptides with affinity for αvβ3-integrins expressed on tumor vascular endothelial cells were coupled to the distal end of PEG on the liposomes sterically stabilized with PEG (long circulating liposomes, LCL). The liposome delivery system was characterized in terms of size, lamellarity, ligand density, drug loading, and leakage properties. Targeting nature of the delivery system was evaluated in vitro using cultured human umbilical vein endothelial cells (HUVEC). Electron microscopic observations of the formulations revealed presence of small unilamellar liposomes of ∼120 nm in diameter. High performance liquid chromatography determination of ligand coupling to the liposome surface indicated that more than 99% of the RGD peptides were reacted with maleimide groups on the liposome surface. Up to 3 mg/mL of stable liposomal combretastatin A4 loading was achieved with ∼80% of this being entrapped within the liposomes. In the in vitro cell culture studies, targeted liposomes showed significantly higher binding to their target cells than non-targeted liposomes, presumably through specific interaction of the RGD with its receptors on the cell surface. It was concluded that the targeting properties of the prepared delivery system would potentially improve the therapeutic benefits of combretastatin A4 compared with nontargeted liposomes or solution dosage forms.
doi:10.1208/pt070232
PMCID: PMC2750290  PMID: 16584166
targeted liposome delivery system; combretastatin A4; tumor vasculature targeting; liposome characterization
22.  Phototriggerable Liposomes: Current Research and Future Perspectives 
Pharmaceutics  2013;6(1):1-25.
The field of cancer nanomedicine is considered a promising area for improved delivery of bioactive molecules including drugs, pharmaceutical agents and nucleic acids. Among these, drug delivery technology has made discernible progress in recent years and the areas that warrant further focus and consideration towards technological developments have also been recognized. Development of viable methods for on-demand spatial and temporal release of entrapped drugs from the nanocarriers is an arena that is likely to enhance the clinical suitability of drug-loaded nanocarriers. One such approach, which utilizes light as the external stimulus to disrupt and/or destabilize drug-loaded nanoparticles, will be the discussion platform of this article. Although several phototriggerable nanocarriers are currently under development, I will limit this review to the phototriggerable liposomes that have demonstrated promise in the cell culture systems at least (but not the last). The topics covered in this review include (i) a brief summary of various phototriggerable nanocarriers; (ii) an overview of the application of liposomes to deliver payload of photosensitizers and associated technologies; (iii) the design considerations of photoactivable lipid molecules and the chemical considerations and mechanisms of phototriggering of liposomal lipids; (iv) limitations and future directions for in vivo, clinically viable triggered drug delivery approaches and potential novel photoactivation strategies will be discussed.
doi:10.3390/pharmaceutics6010001
PMCID: PMC3978522  PMID: 24662363
lipid-based nanoparticles; drug delivery; laser; cancer therapy; photodynamic therapy; liposomes; phototriggering; cancer nanomedicine
23.  OA01. 35. Role of matravasti as rasayana in jarajanya vikara - A clinical study 
Ancient Science of Life  2012;32(Suppl 1):S35.
Purpose:
To prove whether Matravasti shows multiple effects on different systems in old people and to substantiate the effects of Matravasti and Rasayana on clinical basis in ageing.
Method:
Eighty two patients - Men of age group 50 - 80 years; Women aged above 45 years or who have attained Menopause and <75 years suffering from common problems of old age irrespective of sex, caste, religion etc. were registered for the study from the OPD of MCD Ayurvedic Dispensary, Krishna Nagar, Delhi and OPD and IPD of PG Dept. of Panchakarma, Madhav vilas hospital, Jaipur. Out of which, 16 patients dropped out did not complete treatment. Matravasti was administered for 21 times with Balashwagandha lakshadi (BAL) Taila on alternate days with a dosage 30 - 80 ml accordingly. After completion of 21 days of Matravasti, all the patients were reviewed for successive 6 months. All the cases were assessed by considering 15 different aspects reflecting the common problems of ageing like Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) etc.,
Result:
The overall effect and maximum benefit observed was FAIR (25 % - 50 %) in 38 cases out of 66 patients. GOOD response (51 - 75 % response) in 26 cases and remaining 2 cases Best response (>75%). And the maximum benefit observed among all the cases is 81.8 % and the least effect was 25 %. Among all clinical parameters considered for the study maximum efficacy was found in sleep disturbances (67.5%) followed with gait balance deficit (56.25%), emotional status (55.1%), urinary incontinence (55%), Mobility (53.96 %), IADL (51.3%), ADL(50.8%), constipation (49.5%), cognitive status (48.78%), pain (48.14%), dyspnoea (47.25%), hearing impairment (42.5%), visual impairment (41.8%), dermatological manifestations (41.17%), and involuntary movements (22.2%).
Conclusion:
Matravasti is a multifaceted and highly effective therapeutic measure in the geriatric conditions.
PMCID: PMC3800913
24.  A Liposomal Drug Platform Overrides Peptide Ligand Targeting to a Cancer Biomarker, Irrespective of Ligand Affinity or Density 
PLoS ONE  2013;8(8):e72938.
One method for improving cancer treatment is the use of nanoparticle drugs functionalized with targeting ligands that recognize receptors expressed selectively by tumor cells. In theory such targeting ligands should specifically deliver the nanoparticle drug to the tumor, increasing drug concentration in the tumor and delivering the drug to its site of action within the tumor tissue. However, the leaky vasculature of tumors combined with a poor lymphatic system allows the passive accumulation, and subsequent retention, of nanosized materials in tumors. Furthermore, a large nanoparticle size may impede tumor penetration. As such, the role of active targeting in nanoparticle delivery is controversial, and it is difficult to predict how a targeted nanoparticle drug will behave in vivo. Here we report in vivo studies for αvβ6-specific H2009.1 peptide targeted liposomal doxorubicin, which increased liposomal delivery and toxicity to lung cancer cells in vitro. We systematically varied ligand affinity, ligand density, ligand stability, liposome dosage, and tumor models to assess the role of active targeting of liposomes to αvβ6. In direct contrast to the in vitro results, we demonstrate no difference in in vivo targeting or efficacy for H2009.1 tetrameric peptide liposomal doxorubicin, compared to control peptide and no peptide liposomes. Examining liposome accumulation and distribution within the tumor demonstrates that the liposome, and not the H2009.1 peptide, drives tumor accumulation, and that both targeted H2009.1 and untargeted liposomes remain in perivascular regions, with little tumor penetration. Thus H2009.1 targeted liposomes fail to improve drug efficacy because the liposome drug platform prevents the H2009.1 peptide from both actively targeting the tumor and binding to tumor cells throughout the tumor tissue. Therefore, using a high affinity and high specificity ligand targeting an over-expressed tumor biomarker does not guarantee enhanced efficacy of a liposomal drug. These results highlight the complexity of in vivo targeting.
doi:10.1371/journal.pone.0072938
PMCID: PMC3751880  PMID: 24009717
25.  Local Targeted Therapy of Liver Metastasis from Colon Cancer by Galactosylated Liposome Encapsulated with Doxorubicin 
PLoS ONE  2013;8(9):e73860.
Since regional drug administration enables to maintain a high drug concentration within tumors, we compared the plasma concentration and biodistribution of doxorubicin (Dox) from drug-loaded conventional liposomes by local or systemic administration. The results demonstrated that drug concentration was substantially improved in liver as well as a decrease in blood and other organs by spleen injection mimicking portal vein perfusion (regional administration). To further investigate the targeted therapeutic effect of galactosylated liposome encapsulated doxorubicin (Dox) by regional administration, liver targeting liposomes were prepared by incorporating galactosylated-DPPE to conventional liposomes. Liposome uptake and targeting were verified in vitro and in vivo by fluorescence microscopy and xenogen IVIS imaging system, respectively. The results showed that galactose targeted liposomes presented a stronger specific cell uptake by human hepatocellular carcinoma HepG2 cells compared to the non-targeted liposomes. In vivo fluorescence imaging showed that the intra-hepatic deposition of conventional and galactosylated liposomes via spleen injection was more than that via tail vein administration, and galactosylated liposomes had higher fluorescent intensity over conventional liposomes in the liver post spleen administration. The anti-tumor effect of various drug administration routes for both liposomal formulations was evaluated using a murine liver metastasis model of colon cancer. The results indicated that tumor progression in the liver and mesenteric lymph nodes was significantly suppressed by Dox-loaded galactosylated liposomes via spleen injection, while no significance was observed in non-targeted formulations. Our data indicated that local perfusion of galactosylated liposomal doxorubicin had a great promise for the treatment of liver metastasis from colon cancer.
doi:10.1371/journal.pone.0073860
PMCID: PMC3770687  PMID: 24040096

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