In situ thermo-co-electroresponsive mucogel for controlled release of bioactive agent

Int J Pharm. 2019 Mar 25:559:255-270. doi: 10.1016/j.ijpharm.2019.01.044. Epub 2019 Jan 26.

Abstract

The purpose of this work was to develop an in situ thermosensitive electro-responsive mucoadhesive gel loaded with bioactive agent (nanocomposite) meant for nose to brain delivery in a controllable manner when electric stimulation is applied. Nanocomposite was developed using a combinatorial blending of chitosan, hydroxypropylmethylcellulose, pluronic F127 and polyaniline which was then loaded with BCNU-Nano-co-Plex (the bioactive agent). The nanocomposite was a liquid at room temperature but formed an in situ mucogel at a temperature of 27.5 ± 0.5 °C. Furthermore, the nanocomposite possessed a redox element which makes it responsive to electrical stimulation (ES). The stimuli responsiveness enabled the formulation to release the bioactive agent when electrical potential was applied and demonstrated a desired 10.28% release of nanoparticles per application cycle. The results further revealed pore formation within the formulation which accommodated the loaded nanoparticles. The release profile also demonstrated a pulsatile release of the bioactive material when subjected to ES. This formulation may therefore be useful as a nose to brain drug delivery system that can be modulated to deliver bioactive agents to the brain via electro-actuation in an "on-off" drug release kinetics by means of an external ES for a controlled nose-to-brain delivery.

Keywords: Electro-responsive; Mucoadhesive; Mucogel; Nanocomposite; Nose-to-brain delivery; Thermosensitive.

MeSH terms

  • Administration, Intranasal / methods
  • Chitosan / chemistry
  • Delayed-Action Preparations / chemistry*
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Gels / chemistry*
  • Hypromellose Derivatives / chemistry
  • Nanoparticles / chemistry
  • Poloxamer / chemistry
  • Polymers / chemistry
  • Temperature

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Gels
  • Polymers
  • Poloxamer
  • Hypromellose Derivatives
  • Chitosan