title: In situ forming implant for controlled delivery of an anti-HIV fusion inhibitor.
abstract: An injectable, phase sensitive, in situ forming, implantable delivery system was developed for enfuvirtide, a therapeutic peptide used in the treatment of HIV infection. The development studies were carried out using poly (D,L-lactide-co-glycolide), a smart, biodegradable polymer. Different formulations were designed, prepared and evaluated by employing response surface, optimal design of experiment technique. The optimized formulation was identified and validated for its performance by using numerical optimization technique. The in vitro evaluation parameters included rheology, compatibility studies, drug release as well as conformational and physicochemical stability studies. In vivo pharmacokinetic parameters and biocompatibility studies were determined in rat models and were statistically analyzed. It was found that the optimized formulation extended the enfuvirtide release and maintained the drug plasma concentration within therapeutically effective range up to 48 h. The optimized formulation maintained physicochemical and conformational stability for at least 6 months and was biocompatible with the animal tissue.
authors.affiliation: UGC Centre for Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Deepak N
authors.initials: DN
authors.lastname: Kapoor
authors.affiliation: UGC Centre for Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Katare
authors.affiliation: UGC Centre for Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India. Electronic address: sanjudhawan@rediffmail.com.
authors.forename: Sanju
authors.initials: S
authors.lastname: Dhawan
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002942:Circular Dichroism; D019610:Cytoprotection; D004337:Drug Carriers; D004339:Drug Compounding; D004343:Drug Implants; D004355:Drug Stability; D000077560:Enfuvirtide; D005549:Foreign-Body Reaction / Q000209:etiology / Q000517:prevention & control; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000737:chemistry* / Q000633:toxicity; D008297:Male; D051379:Mice; D008954:Models, Biological; D008956:Models, Chemical; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012212:Rheology; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004337:Drug Carriers; D004343:Drug Implants; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid