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1.  Biomaterials/Tissue Interactions: Possible Solutions to Overcome Foreign Body Response 
The AAPS Journal  2010;12(2):188-196.
In recent years, a variety of biomaterial implantable devices has been developed. Of particular significance to pharmaceutical sciences is the progress made on the development of drug/implantable device combination products. However, the clinical application of these devices is still a critical issue due to the host response, which results from both the tissue trauma during implantation and the presence of the device in the body. Accordingly, the in vivo functionality and durability of any implantable device can be compromised by the body response to the foreign material. Numerous strategies to overcome negative body reactions have been reported. The aim of this review is to outline some key issues of biomaterial/tissue interactions such as foreign body response and biocompatibility and biocompatibility assessment. In addition, general approaches used to overcome the in vivo instability of implantable devices are presented, including (a) biocompatible material coatings, (b) steroidal and nonsteroidal anti-inflammatory drugs, and (c) angiogenic drugs. In particular, strategies to overcome host response to glucose biosensors are summarized.
doi:10.1208/s12248-010-9175-3
PMCID: PMC2844517  PMID: 20143194
biocompatible coating for implantable devices; foreign body response (FBR); glucose biosensor; tissue compatibility assessment, drug device combination products
2.  Controlled release of dexamethasone from PLGA microspheres embedded within polyacid-containing PVA hydrogels 
The AAPS Journal  2005;7(1):E231-E240.
The development of zero-order release systems capable of delivering drug(s) over extended periods of time is deemed necessary for a variety of biomedical applications. We hereby describe a simple, yet versatile, delivery platform based on physically cross-linked poly(vinyl alcohol) (PVA) microgels (cross-linked via repetitive freeze/thaw cycling) containing entrapped dexamethasone-loaded poly(lacticco-glycolic acid) (PLGA) microspheres for controlled delivery over a 1-month period. The incorporation of polyacids, such as humic acids, Nafion, and poly(acrylic acid), was found to be crucial for attaining approximately zero-order release kinetics, releasing 60% to 75% of dexamethasone within 1 month. Microspheres alone entrapped in the PVA hydrogel resulted in negligible drug release during the 1-month period of investigation. On the basis of a comprehensive evaluation of the structure-property relationships of these hydrogel/microsphere composites, in conjunction with their in vitro release performance, it was concluded that these polyacids segregate on the PLGA microsphere surfaces and thereby result in localized acidity. These surface-associated polyacids appear to cause acid-assisted hydrolysis to occur from the surface inwards. Such systems show potential for a variety of localized controlled drug delivery applications such as coatings for implantable devices.
doi:10.1208/aapsj070122
PMCID: PMC2751512  PMID: 16146344
hydrogels; microspheres; controlled drug delivery; dexamethasone
3.  DNA-based therapeutics and DNA delivery systems: A comprehensive review 
The AAPS Journal  2005;7(1):E61-E77.
The past several years have witnessed the evolution of gene medicine from an experimental technology into a viable strategy for developing therapeutics for a wide range of human disorders. Numerous prototype DNA-based biopharmaceuticals can now control disease progression by induction and/or inhibition of genes. These potent therapeutics include plasmids containing transgenes, oligonucleotides, aptamers, ribozymes, DNAzymes, and small interfering RNAs. Although only 2 DNA-based pharmaceuticals (an antisense oligonucleotide formulation, Vitravene, (USA, 1998), and an adenoviral gene therapy treatment, Gendicine (China, 2003), have received approval from regulatory agencies; numerous candidates are in advanced stages of human clinical trials. Selection of drugs on the basis of DNA sequence and structure has a reduced potential for toxicity, should result in fewer side effects, and therefore should eventually yield safer drugs than those currently available. These predictions are based on the high selectivity and specificity of such molecules for recognition of their molecular targets. However, poor cellular uptake and rapid in vivo degradation of DNA-based therapeutics necessitate the use of delivery systems to facilitate cellular internalization and preserve their activity. This review discusses the basis of structural design, mode of action, and applications of DNA-based therapeutics. The mechanisms of cellular uptake and intracellular trafficking of DNA-based therapeutics are examined, and the constraints these transport processes impose on the choice of delivery systems are summarized. Finally, the development of some of the most promising currently available DNA delivery platforms is discussed, and the merits and drawbacks of each approach are evaluated.
doi:10.1208/aapsj070109
PMCID: PMC2751499  PMID: 16146351
nucleic acid therapeutics; DNA delivery systems; nonviral vectors; viral vectors; liposomes; gene therapy
4.  Anionic liposomal delivery system for DNA transfection 
The AAPS Journal  2004;6(4):13-22.
The present study investigates the use of novel anionic lipoplexes composed of physiological components for plasmid DNA delivery into mammalian cells in vitro. Liposomes were prepared from mixtures of endogenously occurring anionic and zwitterionic lipids, 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt) (DOPG) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), respectively, at a molar ratio of 17∶83 (DOPG:DOPE). Anionic lipoplexes were formed by complexation between anionic liposomes and plasmid DNA molecules encoding green fluorescence protein (GFP) using Ca2+ ions. Transfection and toxicity were evaluated in CHO-K1 cells using flow cytometry and propidium iodide staining, respectively. Controls included Ca2+-DNA complexes (without lipids), anionic liposomes (no Ca2+), and a cationic liposomal formulation. Efficient delivery of plasmid DNA and subsequent GFP expression was achieved using anionic lipoplexes. Transfection efficiency increased with Ca2+ concentration up to 14 mM Ca2+, where transfection efficiency was 7-fold higher than in untreated cells, with minimum toxicity. Further increase in Ca2+ decreased transfection. Transfection efficiency of anionic lipoplexes was similar to that of cationic liposomes (lipofect Amine), whereas their toxicity was significantly lower. Ca2+-DNA complexes exhibited minimal and irregular transfection with relatively high cytotoxicity. A model was developed to explain the basis of anionic lipoplex uptake and transfection efficacy. Effective transfection is explained on the formation of nonbilayer hexagonal lipid phases. Efficient and relatively safe DNA transfection using anionic lipoplexes makes them an appealing alternative to be explored for gene delivery.
doi:10.1208/aapsj060429
PMCID: PMC2751225  PMID: 15760094
anionic liposomes; gene delivery; transfection; nonviral vector; lipoplex; flow cytometry
5.  Particle size analysis: AAPS workshop report, cosponsored by the Food and Drug Administration and the United States Pharmacopeia 
The AAPS Journal  2004;6(3):23-34.
The concepts of particle engineering and dosage form design have become dominant themes in pharmaceutical manufacturing. This trend is not simply a reflection of the development of new, more sophisticated manufacturing methods of particles or dispersed systems but also recognition of the importance of quality control even in more traditional manufacturing processes. However, the diversity of particle treatments, methods of particle size analysis, expression and interpretation of data, and process applications results in complicated and sometimes confusing criteria for selection, adoption, or relevance of the available techniques.
doi:10.1208/aapsj060320
PMCID: PMC2751245  PMID: 15760105

Results 1-5 (5)