title: In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization.
abstract: OBJECTIVE
  The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.
  
  
  METHODS
  Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.
  
  
  CONCLUSIONS
  There was a big deviation between the Tg of the polymeric caplet from the Tg's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012-0.332 mg/mL and 0.009-0.256 mg/mL for AZT and PSS over 1-28 d.
  
  
  CONCLUSIONS
  The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutic Sciences, University of the Witwatersrand , Johannesburg, Parktown , South Africa .
authors.forename: Valence M K
authors.initials: VM
authors.lastname: Ndesendo
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Leith C R
authors.initials: LC
authors.lastname: Meyer
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Lomas K
authors.initials: LK
authors.lastname: Tomar
authors.forename: Charu
authors.initials: C
authors.lastname: Tyagi
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000268:Adhesiveness / Q000187:drug effects; D000282:Administration, Intravaginal; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology; D015497:HIV-1 / Q000187:drug effects*; D015394:Molecular Structure; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D013552:Swine; D014014:Tissue Adhesives / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D011108:Polymers; D014014:Tissue Adhesives
keywords: Histopathological studies; mucoadhesive polymeric caplet; polymeric-controlled drug release; temperature-modulated differential scanning calorimetry