Radiosynovectomy is a therapy used to relieve pain and inflammation from rheumatoid arthritis and related diseases. In this study three 188Re particulate compounds were characterized according to their physico-chemical properties and their biological behavior in rabbits. The results were compared in order to establish which was the radiopharmaceutical that better fits the requirements of this kind of radiotherapy.
Three radiopharmaceutical formulations, tin colloid, hydroxyapatite particles (HA) and ferric hydroxide macroaggregates coated with tin colloid (FHMA), were physically characterized (number, volume and surface of the particles). For this purpose laser diffraction methodology was used. To evaluate cavity leakage of activity the following studies in New Zealand rabbits were performed: scintigraphic images for 48 hr after intraarticular injection of each radiopharmaceutical, biodistribution at 48 hr and urine samples collection during the first 24 hr post-radiopharmaceutical administration.
Labeling procedures for 188Re-HA and 188Re-Sn-FHMA were labour intensive while 188Re-Sn was easily prepared. Furthermore, 188Re-Sn colloid offered the greatest surface area in the 2–10 microm range and was obtained with a radiochemical purity over 95%, while percentage of bound activity for 188Re-HA and 188Re-Sn-FHMA were 55% and 92% respectively. Stability was verified for the three radiopharmaceuticals for 24 hr. Scintigraphic studies and biodistribution in rabbits after intraarticular administration of the radiopharmaceuticals showed relevant activity only in the knee, this being over 90% of the residual activity in the whole body at 48 hr in every case. Renal elimination of 188Re-Sn colloid and 188Re-Sn-FHMA was detected by activity measurements in urine samples, during the first 12 hr post-radiopharmaceutical injection.
The percentage of activity retained in the knee was 69.1% for 188Re-Sn colloid, 55.1% for 188Re-Sn-FHMA and 33.6% for 188Re-HA.
The 188Re-Sn colloid was easy to prepare, minimum facilities were required, was stable for 24 hr and showed minimal leakage from the joint after intraarticular injection into the rabbit's knee. Furthermore, 188Re-Sn colloid has greater retention in the knee when it is compared with the other radiopharmaceuticals, so it could provide the best therapeutic effect/absorbed dose ratio for the patient.
Objective: We aimed to assess the role of Magnetic Resonance Imaging (MRI) and X-Ray in the evaluation of response to radiosynovectomy (RS) in patients with hemophilic arthropathy.
Material and Methods: Eleven patients who suffered from hemophilic arthropathy with a mean age of 11.7 (range between 7-15) were included in this study. 148-185 MBq Yttrium 90 silicate (Y-90) was administered intraarticularly to ten knee joints and one patient was treated with intraarticular 74 MBq Rhenium 186 (Re-186) injection into his ankle. Before radiosynovectomy, plain anteroposterior and lateral X-rays of the target joints were obtained by standard technique. The follow-up MRI and X-ray studies of the patients were done 6 months after RS. Pettersson hemophilic arthropathy scales were utilized to stage the condition of the joints on plain X-ray and classification of the investigated joints on MRI were done according to Denver score. The clinical assessment of the efficacy of the RS was made with the comparison of the average bleedings before and after the intervention.
Results: During the 6-month follow-up period after RS, an improvement in number of hemarthrosis 75% or greater compared with the prior six months occurred in six joints (54.5%). The Pettersson scores worsened in 1/11 (9%), remained unchanged in 9/11 (81.8%), and improved in 1/11 (9%) joints. At the 6-month follow-up, the MRI score worsened in one (9%) and was unchanged in 10/11 joints (90.9%).
Conclusion: MRI is a more sensitive tool than plain radiography for evaluating and follow-up of joint disease in persons with hemophilia, but both methods don’t show correlation with the therapeutic response
Conflict of interest:None declared.
Radiosynovectomy; hemophilic arthropathy; magnetic resonance imaging; therapy response
After surgical therapy of diffuse pigmented villonodular synovitis (DPVNS), recurrence is seen in almost half of the patients. The effectiveness of radiosynovectomy (RSV) in preventing recurrence and complaints of DPVNS is well known. Elbow involvement in DPVNS is a very rare condition; therefore, RSV in elbow hasn’t been experienced widely. The aim of this case report is to show the effectiveness of RSV with rhenium-186 (Re-186) sulfide colloid. We applied Re-186 sulfide colloid to the elbow joint of DPVNS patients six weeks after arthroscopic synovectomy. As a result, the patient did not have any complaints, and our findings are compatible with residue or recurrence on magnetic resonance imaging (MRI) in sixth and twentieth month controls after administration. We concluded that Re-186 is an effective adjuvant therapy for the prevention of recurrence and complaints.
Rhenium-186 (Re-186); Radiosynovectomy; Elbow; Diffuse Pigmented Villonodular Synovitis (DPVNS)
Radisosynovectomy (RS) is a local form of radionuclide therapy used in various forms of arthritis characterized by synovitis. In hemophilic arthropathy, RS provides removal of inflamed synovium and prevents further joint damage. This review focuses on the practical aspects of radionuclide synovectomy in hemophilic patients and describes the issues both related to the methodology and post-therapeutic follow-up.
Conflict of interest:None declared.
radioisotope therapy; Hemophilia; synovitis
OBJECTIVES--The aim of this study was to evaluate the long term effect of radiation synovectomy with yttrium-90 silicate in haemophiliac patients with recurrent haemarthrosis. METHODS--The bleeding frequency and the mobility of the joint were recorded in 16 joints of 14 patients 1 year before radiosynovectomy and during follow up, which ranged from 3 to 6 years. Patients evaluated the effect of their own treatment by completing a questionnaire. Radiographs of the joints were scored by an independent radiologist before treatment. RESULTS--A satisfactory reduction of the frequency of haemorrhage was achieved in 94% of joints during the first year after treatment and was maintained in 63% until the end of the follow up period. In general there was no decrease in mobility attributable to radiosynovectomy, and the patients' own evaluations agreed with the evaluations based on the frequencies of haemarthrosis in 75%. Patients who had only minor, or no, radiological abnormalities of the joints before treatment showed the best results. One patient developed synovitis as a complication of the radiosynovectomy. CONCLUSION--Radiosynovectomy is an effective and safe treatment for recurrent haemarthrosis in haemophiliac patients, especially in those who have joints with no or minor radiological damage.
Treatment of extensive diffuse pigmented villonodular synovitis (PVNS) of large joints by isolated surgical resection is unsatisfactory, with high rates of local recurrence. Post-synovectomy adjuvant treatment with external beam radiation therapy or intra-articular injection of radioactive material as yttrium-90 (90Y) yielded better results. Between January 2005 and January 2007, 12 patients (eight men and four women aged 19–49 years) with extensive diffuse PVNS of the knee were treated. All patients had an adjuvant post-operative external beam radiation therapy (2,600–3,000 cGy) conventionally fractionated 200 cGy/fraction, five fractions/week, 6–8 weeks after surgery. Mean follow-up time was 27 months (range from 20 to 36 months). All patients were followed up using clinical assessment, magnetic resonance imaging, and plain X-ray. In all patients, neither evidence of disease recurrence nor progression of bone or articular destruction was noted. No complications were noticed after surgery or after post-operative external beam radiation therapy. A combination of debulking surgery using anterior and posterior approach with adjuvant post-operative external beam radiation therapy for extensive diffuse PVNS of the knee joint is a reliable treatment method, with good results in regard to the incidence of local recurrence and functional outcome.
PVN; synovitis; radiosynovectomy; synovectomy
Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC188Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC188Re-SSS in a chemically induced hepatocellular carcinoma rat model.
Animals were treated with an injection of LNC188Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, n = 12; 120 MBq, n = 11) were compared with sham (n = 12), blank LNC (n = 7) and 188Re-perrhenate (n = 4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC188Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC188Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process.
Overall, these results demonstrate that internal radiation with LNC188Re-SSS is a promising new strategy for hepatocellular carcinoma treatment.
Previous studies on the same group of patients investigated here demonstrated the effectiveness of radiosynovectomy in the treatment of chronic haemophilic synovitis even if one, two or three radiosynovectomy procedures (RS-1, RS-2, RS-3) may be necessary. The purpose of this study was to determine whether the joints’ response to each radiosynovectomy procedure behaved independently or not.
Materials and methods
One hundred and fifty-six radiosynovectomies were performed in 104 joints of 78 people diagnosed with chronic haemophilic synovitis. The patient’s mean age was 18 years. Fifty-eight patients required radiosynovectomy in a single joint, whereas 20 received treatment in more than one joint. Of the 104 joints subjected to radiosynovectomy, 33 were elbows, 47 knees and 24 ankles. Radiosynovectomy was carried out with either yttrium-90 or rhenium-186 (1–3 injections with 6-month intervals between them). Of the 104 joints, 68 required a single injection of the radioisotope (RS-1), 20 required two injections (RS-2) and 16 required three injections (RS-3). In eight cases (7.6%), the affected joints eventually required surgery.
An analysis of seven variables (number of bleeding episodes, articular pain, range of motion in flexion and extension, muscle strength in flexion and extension, and synovial thickness by imaging) demonstrated that each consecutive radiosynovectomy behaves independently in haemophilic synovitis.
Each consecutive radiosynovectomy behaves independently in haemophilic synovitis. This finding had not been documented in the literature before the present study.
haemophilia; synovitis; radiosynovectomy
Radiosynovectomy is a novel method of treatment for several acute and chronic inflammatory joint disorders. A small amount of a beta-emitting radionuclide is injected into the affected joint delivering a radiation dose of 70 to 100 Gy to the synovia. The proliferative tissue is destroyed, secretion of fluid and accumulation of inflammation causing cellular compounds stops and the joint surfaces become fibrosed, providing long term symptom relief. The radionuclides are injected in colloidal form so that they remain in the synovium and are not transported by lymphatic vessels causing radiation exposure to other organs. Complete reduction of knee joint swelling has been seen in above 40% and pain relief in 88% of patients. Wrist, elbow, shoulder, ankle and hip joints showed significant improvement in 50-60% and restoration of normal function and long term pain relief has been achieved in about 70% of small finger joints. In hemophilic arthropathies complete cessation of bleeding in about 60% and improved mobility in 75% of patients has been reported.
Radiosynovectomy; treatment of hemophilic arthropathies; radionuclides in rheumatoid arthritis
Objective(s): In this work a new possible agent for radiosynovectomy has been targeted for articular pain palliation.
Materials and Methods: Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4 × 1013 n.cm-2.s-1. The product was converted into chloride form which was further used for labeling of 177Lu-phytate complex and checked using ITLC (MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase). The complex stability and viscosity were checked in the final solution up to seven days. The prepared complex solution (100 µCi/100 µl) was injected intra-articularly to male rat knee joint. Leakage of radioactivity from injection site and its distribution in organs were investigated up to seven days.
Results: The complex was successfully prepared with high radiochemical purity (>99.9 %). Approximately, the whole injected dose has remained in injection site seven days after injection.
Conclusion: The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology.
Biodistribution; Lutetium-177; Phytate Radiosynovectomy
66Ho-chloride was obtained by bombardment of natural Ho(NO3)3 dissolved in acidic media using thermal neutron flux (4-5 × 1013 n.cm-2.s-1).
166Ho-holmium chloride (185 MBq) was used successfully for preparation of 166Ho-phytate complex with high radiochemical purity (>99.9 %, ITLC, MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase). The complex stability and viscosity were checked in the final solution up to 2 days. The prepared complex solution (60 μCi/100 μl) was injected intraarticularly to male rat knee joints. Leakage of radioactivity from the injection site and its distribution in organs were investigated up to 2 days.
Approximately all of the injected dose had remained in the injection site 2 days after injection.
The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology.
Phytate; Radiosynovectomy; Holmium-166; Biodistribution; SPECT
The aim of this study was to formulate a new delivery system for ecological pesticides by the incorporation of Artemisia arborescens L essential oil into solid lipid nanoparticles (SLN). Two different SLN formulations were prepared following the high-pressure homogenization technique using Compritol 888 ATO as lipid and Poloxamer 188 or Miranol Ultra C32 as surfactants. The SLN formulation particle size was determined using Photon correlation spectroscopy (PCS) and laser diffraction analysis (LD). The change of particle charge was studied by zeta potential (ZP) measurements, while the melting and recrystallization behavior was studied using differential scanning calorimetry (DSC). In vitro release studies of the essential oil were performed at 35°C. Data showed a high physical stability for both formulations at various storage temperatures during 2 months of investigation. In particular, average diameter of Artemisia arborescens L essential oil-loaded SLN did not vary during storage and increased slightly after spraying the SLN dispersions. In vitro release experiments showed that SLN were able to reduce the rapid evaporation of essential oil if compared with the reference emulsions. Therefore, obtained results showed that the studied SLN formulations are suitable carriers in agriculture.
solid lipid nanoparticles; SLN; natural pesticide; in vitro release; agriculture
Rhenium-188 (188Re) displays abundant intermediate energy β emission and possesses a physical half-life of 16.9 h. Sorafenib is an orally available multikinase inhibitor that targets Raf kinases and vascular endothelial growth factor receptors (VEGFRs). Sorafenib has demonstrated preclinical and clinical activity against several types of tumors, such as renal cell and colorectal carcinoma. In this study, we investigated the efficacy of radiotherapeutics of 188Re-liposomes combined with sorafenib in a C26-luc metastatic colorectal liver tumour mouse model. Liver metastases were established by intrasplenic injection of C26-luc murine colon cancer cells. Based on the results of the toxicity assessment, an administration dose of 80% the maximum tolerated dose was selected. 188Re-liposomes were administered on day 1, when metastases of several hundred micrometers in diameter were observed. In the combination therapy group, 10 mg/kg sorafenib (co-developed and co-marketed by Bayer and Onyx Pharmaceuticals as Nexavar) was administered every other day for 1 week and the survival of mice was assessed. The tumor growth was more significantly inhibited in the 188Re-liposome plus sorafenib group compared with the 188Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). Furthermore, 188Re-liposomes combined with sorafenib achieved higher survival rates compared with the 188Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). These results support the use of combined radio-chemotherapy with 188Re-liposomes plus sorafenib as a viable treatment option in the adjuvant setting for liver metastases of colorectal cancer.
liver metastasis; liposomes; rhenium-188; colon cancer; radiotherapy
Solids dispersions (SDs) have been proposed as an alternative to improve the dissolution rate of low solubility drugs. SDs containing albendazole (ABZ; 5, 10, 25, and 50% w/w) and Pluronic 188 (P 188) as hydrophilic carrier were formulated. The obtained SDs were assessed in comparison to physical mixtures (PMs). Drug–polymer interactions in solid state were investigated using Fourier-transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction analysis. No chemical interaction was found between ABZ and poloxamer. The dissolution profiles indicated that ABZ incorporated in SDs and PMs was rapidly released, reaching rapidly the steady state. Increased dissolution rates are usually observed at the highest polymer proportions. However, an opposite effect for SDs as well as for PMs was observed in the assays described here. The systems with the lowest P 188 percentages (SD4, SD3; PM4, PM3) tended to be more effective in increasing the ABZ dissolution rate. Such a result can be attributed to the fact that concentrated aqueous solutions of Poloxamer may form thermo-reversible gels. The physical–mechanical properties indicated that SDs possess improved flow and compacting properties compared to PMs. Thus, ABZ SDs would be more convenient for solid dosage form design and manufacture.
albendazole; dissolution rate; poloxamer; solid dispersions; surfactant
The purpose of this study was to develop intraperitoneal hyperthermic therapy based on magnetic fluid hyperthermia, nanoparticle-wrapped cisplatin chemotherapy, and magnetic particles of albumin. In addition, to combine the multiple-killing effects of hyperthermal targeting therapy, chemotherapy, and radiotherapy, the albumin-nanoparticle surfaces were linked with radionuclide 188Re-labeled folic acid ligand (188Re-folate-CDDP/HSA).
Human serum albumin was labeled with 188Re using the pre-tin method. Reaction time and optimal conditions of labeling were investigated. The particles were intravenously injected into mice, which were sacrificed at different time points. Radioactivity per gram of tissue of percent injected dose (% ID/g) was measured in vital organs. The biodistribution of 188Re-folate-CDDP/HAS magnetic nanoparticles was assessed.
Optimal conditions for 188Re-labeled folate-conjugated albumin combined with cisplatin magnetic nanoparticles were: 0.1 mL of sodium gluconate solution (0.3 mol/L), 0.1 mL of concentrated hydrochloric acid with dissolved stannous chloride (10 mg/mL), 0.04 mL of acetic acid buffer solution (pH 5, 0.2 mol/L), 30 mg of folate-conjugated albumin combined with cisplatin magnetic nanoparticles, and 188ReO4 eluent (0.1 mL). The rate of 188Re-folate-CDDP-HSA magnetic nanoparticle formation exceeded 90%, and radiochemical purity exceeded 95%. The overall labeling rate was 83% in calf serum at 37°C. The major uptake tissues were the liver, kidney, intestine, and tumor after the 188Re-folate-CDDP/HSA magnetic nanoparticles were injected into nude mice. Uptake of 188Re-folate-CDDP/HSA magnetic nanoparticles increased gradually after injection, peaked at 8 hours with a value of 8.83 ± 1.71, and slowly decreased over 24 hours in vivo.
These results indicate that 188Re-folate-CDDP/HSA magnetic nanoparticles can be used in radionuclide-targeted cancer therapy. Surface-modified albumin nanoparticles with folic acid ligand-labeled radionuclide (188Re) were successfully prepared, laying the foundation for a triple-killing effect of thermotherapy, chemotherapy, and radiation therapy.
cisplatin; folic acid; albumin; magnetic nanoparticles; 188Re; ovarian cancer
Our previous results indicated that the plasma membrane of cultured normal rat kidney fibroblastic cell is compartmentalized for diffusion of receptor molecules, and that long-range diffusion is the result of successive intercompartmental jumps (Sako, Y. and Kusumi, A. 1994. J. Cell Biol. 125:1251-1264). In the present study, we characterized the properties of intercompartmental boundaries by tagging transferrin receptor (TR) with either 210-nm-phi latex or 40-nm-phi colloidal gold particles, and by dragging the particle-TR complexes laterally along the plasma membrane using laser tweezers. Approximately 90% of the TR- particle complexes showed confined-type diffusion with a microscopic diffusion coefficient (Dmicro) of approximately 10(-9) cm2/s and could be dragged past the intercompartmental boundaries in their path by laser tweezers at a trapping force of 0.25 pN for gold-tagged TR and 0.8 pN for latex-tagged TR. At lower dragging forces between 0.05 and 0.1 pN, particle-TR complexes tended to escape from the laser trap at the boundaries, and such escape occurred in both the forward and backward directions of dragging. The average distance dragged was half of the confined distance of TR, which further indicates that particle- TR complexes escape at the compartment boundaries. Since variation in the particle size (40 and 210 nm, the particles are on the extracellular surface of the plasma membrane) hardly affects the diffusion rate and behavior of the particle-TR complexes at the compartment boundaries, and since treatment with cytochalasin D or vinblastin affects the movements of TR (Sako and Kusumi as cited above), argument has been advanced that the boundaries are present in the cytoplasmic domain. Rebound of the particle-TR complexes when they escape from the laser tweezers at the compartment boundaries suggests that the boundaries are elastic structures. These results are consistent with the proposal that the compartment boundaries consist of membrane skeleton or a membrane-associated part of the cytoskeleton (membrane skeleton fence model). Approximately 10% of TR exhibited slower diffusion (Dmicro approximately 10(-10)-10(-11) cm2/s) and binding to elastic structures.
Estimating the colloidal stability of polymeric nanoparticles (NPs) in biological environments is critical for designing optimal preparations and to clarify the fate of these devices after administration. To characterize and quantify the physical stability of nanodevices suitable for biomedical applications, spherical NPs composed of poly-lactic acid (PLA) and poly-methyl-methacrylate (PMMA), in the range 100–200 nm, were prepared. Their stability in salt solutions, biological fluids, serum and tissue homogenates was analyzed by dynamic light scattering (DLS). The PMMA NPs remained stable in all fluids, while PLA NPs aggregated in gastric juice and spleen homogenate. The proposed stability test is therefore useful to see in advance whether NPs might aggregate when administered in vivo. To assess colloidal stability ex vivo as well, spectrophotofluorimetric analysis was employed, giving comparable results to DLS.
Nanoparticles; Poly-lactic acid; Poly-methyl-methacrylate; Nanomedicine; Gastrointestinal fluids; Serum; Homogenates
molecules play an important role in biological and chemical
processes, but physical effects due to their symmetry-breaking are
generally weak. Several physical chiral separation schemes which could
potentially be useful, including the propeller effect, have therefore
not yet been demonstrated at the molecular scale. However, it has
been proposed that complex nonspherical colloidal particles could
act as “colloidal molecules” in mesoscopic model systems
to permit the visualization of molecular phenomena that are otherwise
difficult to observe. Unfortunately, it is difficult to synthesize
such colloids because surface minimization generally favors the growth
of symmetric particles. Here we demonstrate the production of large
numbers of complex colloids with glancing angle physical vapor deposition.
We use chiral colloids to demonstrate the Baranova and Zel’dovich
(BaranovaN. B.Zel’dovichB. Y.Chem.
Phys. Lett.1978, 135, 435) propeller effect: the separation of a racemic
mixture by application of a rotating field that couples to the dipole
moment of the enantiomers and screw propels them in opposite directions.
The handedness of the colloidal suspensions is monitored with circular
differential light scattering. An exact solution for the colloid’s
propulsion is derived, and comparisons between the colloidal system
and the corresponding effect at the molecular scale are made.
We are developing tablet dosage forms for implantation directly into the subconjunctival space of the eye. The matrix metalloproteinase inhibitor, ilomastat, has previously been shown to be efficacious at suppressing scarring following glaucoma filtration surgery (GFS). We report on the physical characterisation of ilomastat which is being developed for ocular implantation. Since ilomastat is being considered for implantation it is necessary to examine its polymorphs and their influence on aspects of the in vitro drug release profile. X-ray powder diffraction identified two polymorphs of ilomastat from different commercial batches of the compound. Tablets were prepared from the two different polymorphs. Isothermal perfusion calorimetry was used to show that amorphous content is not increased during tablet formulation. The melting points of the two polymorphs are 188 and 208°C as determined by differential scanning calorimetry. Utilising single crystal X-ray diffraction, the structural conformations and packing arrangements of the different polymorphs were determined. The orthorhombic crystal crystallised as a monohydrate while the second monoclinic crystal form is non-solvated. Ilomastat tablets prepared from the two different solid forms exhibited similar drug release profiles in vitro under conditions mimicking the aqueous composition, volume and flow of the subconjunctival space after GFS. This suggests that a reproducible dose at each time point during release after implantation should be achievable in vivo with ilomastat tablets prepared from the two polymorphs identified.
ocular drug delivery; enantiotrope; dissolution; biorelevant media; solid–solid transition
Laser ablation of solids in liquids technique has been used to obtain colloidal nanoparticles from biological hydroxylapatite using pulsed as well as a continuous wave (CW) laser. Transmission electron microscopy (TEM) measurements revealed the formation of spherical particles with size distribution ranging from few nanometers to hundred nanometers and irregular submicronic particles. High resolution TEM showed that particles obtained by the use of pulsed laser were crystalline, while those obtained by the use of CW laser were amorphous. The shape and size of particles are consistent with the explosive ejection as formation mechanism.
Solid lipid nanoparticles are typically spherical with an average diameter between 1 and 1000 nm. It is an alternative carrier system to tradition colloidal carriers, such as, emulsions, liposomes, and polymeric micro and nanoparticles. Ramipril is an antihypertensive agent used in the treatment of hypertension. Its oral bioavailability is 28% and it is rapidly excreted through the renal route. This drug has many side effects such as, postural hypotension, hyperkalemia, and angioedema, when given as an immediate dosage form. To overcome the side effects and to increase the bioavailability of ramipril, solid lipid nanoparticles of ramipril are prepared by using lipids (glyceryl monostearate and glyceryl monooleate) with stabilizers (tween 80, poloxamer 188, and span 20). The prepared formulations have been evaluated for entrapment efficiency, drug content, in-vitro drug release, particle size analysis, scanning electron spectroscopy, Fourier transform-infrared studies, and stability. A formulation containing glyceryl monooleate, stabilized with span 20 as surfactant showed prolonged drug release, smaller particle size, and narrow particle size distribution, as compared to other formulations with different surfactants and lipids.
Colloidal carriers; ramipril; lipid matrix; surfactants; entrapment efficiency
Formulation of insulin into a microemulsion very often presents a physicochemical instability during their preparation and storage. In order to overcome this lack of stability and facilitate the handling of these colloidal systems, stabilization of insulin in presence of hydrophobic components of a microemulsion appears as the most promising strategy. The present paper reports the use of egg yolk for stabilization of insulin in self microemulsifying dispersions. Insulin loaded egg yolk self microemulsifying dispersions were prepared by lyophilization followed by dispersion into self microemulsifying vehicle. The physicochemical characterization of selfmicroemulsifying dispersions includes such as insulin encapsulation efficiency, in vitro stability of insulin in presence of proteolytic enzymes and in vitro release. The biological activity of insulin from the dispersion was estimated by enzyme-linked immunosorbant assay and in vivo using Wistar diabetic rats. The particle size ranged 1.023±0.316 μm in diameter and insulin encapsulation efficiency was 98.2±0.9 %. Insulin hydrophobic self microemulsifying dispersions suppressed insulin release in pH 7.4 phosphate buffer and shown to protect insulin from enzymatic degradation in vitro in presence of chymotripsin. Egg yolk encapsulated insulin was bioactive, demonstrated through both in vivo and in vitro.
Insulin; egg yolk; microemulsion; in vitro stability; oral delivery
Recent advances in the synthesis of polymeric colloids have opened the doors to new advanced materials. There is strong interest in using these new techniques to produce particles that mimic and/or interact with biological systems. An important characteristic of biological systems that has not yet been exploited in synthetic polymeric colloids is their wide range of deformability. A canonical example of this is the human red blood cell (RBC) which exhibits extreme reversible deformability under flow. Here we report the synthesis of soft polymeric colloids with sizes and shapes that mimic those of the RBC. Additionally, we demonstrate that the mechanical flexibility of the colloids can be reproducibly varied over a large range resulting in RBC-like deformability under physiological flow conditions. These materials have the potential to impact the interaction between biological and synthetic systems.
crosslinking; deformable; hydrogel; microparticle; stop flow lithography
Human Papillomavirus (HPV) infection is considered a necessary step for the development of cervical cancer and >95% of all cervical cancers have detectable HPV sequences. We have recently demonstrated the efficacy of radioimmunotherapy (RIT) which targeted viral oncoprotein E6 in treatment of experimental cervical cancer We hypothesized that pre-treatment of tumor cells with various agents which cause cell death and/or elevation of E6 levels would increase the accumulation of radiolabeled antibodies to E6 in cervical tumors.
HPV-16 positive CasKi cells were treated in vitro with up to 6 Gy of external radiation, or proteasome inhibitor MG-132 or unlabeled anti-E6 antibody C1P5 and cell death was assessed. Biodistribution of 188Rhenium (188Re)-labeled C1P5 antibody was performed in both control and radiation MG-132 treated CasKi tumor-bearing nude mice.
. 188Re-C1P5 antibody demonstrated tumor specificity and very low uptake and fast clearance from the major organs. The amount of tumor uptake was enhanced by MG-132 but was unaffected by pre-treatment with radiation. In addition, in vitro studies demonstrated an unanticipated effect of unlabeled antibody on the amount of cell death, a finding that was suggested by our previous in vivo studies in CasKi tumor model.
We demonstrated that pre-treatment of cervical tumors with proteasome inhibitor MG-132 and with unlabeled antibody to E6 can serve as a means to generate non-viable cancer cells and to elevate the levels of target oncoproteins in the cells for increasing the accumulation of targeted radiolabeled antibodies in tumors. These results favor further development of RIT of cervical cancers targeting viral antigens.
Cervical cancer; viral antigens; radiolabeled antibodies; 188-Rhenium; chemotherapy
Colloidal crystals of polymeric or inorganic microspheres are of extensive interest due to their potential applications in such as sensing, optics, photonic bandgap and surface patterning. The article highlights a set of approaches developed in our group, which are efficient to prepare colloidal crystals with ordered voids, patterned colloidal crystals on non-planar surfaces, heterogeneous colloidal crystals of different building blocks, colloidal crystals composed of non-spherical polyhedrons, and colloidal crystals of non-close-packed colloidal microspheres in particular. The use of these colloidal crystals as templates for different microstructures range from nanoscale to micron-scale is also summarized.
Colloidal crystal; Nanostructure; Surface patterning