Development and in vivo evaluation of an implantable nano-enabled multipolymeric scaffold for the management of AIDS dementia complex (ADC)

Int J Pharm. 2015 Dec 30;496(2):863-77. doi: 10.1016/j.ijpharm.2015.10.025. Epub 2015 Oct 9.

Abstract

This study reports the use of biocompatible and biodegradable polymers for the formulation and design of an implantable multipolymeric drug delivery device (MDDD) for the management of AIDS dementia complex (ADC), a debilitating condition affecting the cognitive, motor and behavioral systems in HIV+ individuals. A 3-factor Box-Behnken statistical design was employed for the optimization of nanoparticle and multipolymeric scaffold formulations. Fifteen formulations were generated using the Box-Behnken template, which were assessed for physicochemical and physicomechanical characterization. The optimised nanoparticle formulation yielded nanoparticles measuring 68.04nm in size and zeta potential (ZP) of -13.4mV was calculated for the colloidal system. In an attempt to further retard drug release and to formulate a device for implantation in the frontal lobe of the brain, nanoparticles were dispersed within a multipolymeric matrix. Matrix erosion was calculated at 28% for multipolymeric scaffold and a matrix resilience of 4.451% was observed 30 days post exposure to PBS, indicating slow degradation of the MDDD. In vivo studies showed 12.793ng/mL and 35.225ng/mL AZT level in plasma and CSF. In view of the physicomechanical properties, in vitro and in vivo drug release kinetics of MDDD makes it a potential candidate for the management of the ADC.

Keywords: AIDS dementia complex management; Implantable device; Nanoparticles; Polymeric scaffold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / pathology
  • AIDS Dementia Complex / therapy*
  • Animals
  • Brain / pathology
  • Chemistry, Pharmaceutical
  • Drug Delivery Systems / instrumentation
  • Humans
  • Male
  • Microscopy, Electron, Scanning
  • Nanoparticles / chemistry
  • Particle Size
  • Rats
  • Rats, Sprague-Dawley
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • Tissue Scaffolds*
  • Zidovudine / pharmacokinetics
  • Zidovudine / therapeutic use

Substances

  • Zidovudine