Development and characterization of PLA nanoparticles for pulmonary drug delivery: Co-encapsulation of theophylline and budesonide, a hydrophilic and lipophilic drug

Mira Dhiraj Buhecha, Alison B. Lansley, Satyanarayana Somavarapu, Ananth S. Pannala

Research output: Contribution to journalArticle

Abstract

Drug encapsulated biodegradable polymeric nanoparticles are suitable for lung delivery of therapeutic molecules. The objective of the current study was to co-encapsulate a hydrophilic drug (theophylline) and a lipophilic drug (budesonide) in poly(lactic acid) (PLA) nanoparticles for pulmonary drug delivery. PLA nanoparticles were produced using a double emulsification solvent diffusion method and characterized for their particle size, zeta potential, drug loading, in vitro drug release, interactions with airway epithelial cell line (16HBE14o-) and in vitro deposition properties upon nebulization. The spherically-shaped mono- and co-encapsulated PLA nanoparticles were observed to have a particle size of 190–400 nm and a zeta potential of −10 to −16mV. Sustained drug release over 24 h was observed from the nanoparticles into a mixture of simulated lung fluid and methanol (1:1), measured using Franz diffusion cells and when assessed for permeability using 16HBE14o-cells. There was no significant reduction in cell viability after 24 h exposure to drug-encapsulated nanoparticles at nebulized concentrations (p > 0.05). Nebulization of co-encapsulated nanoparticles resulted in a fine particle fraction of 75% and 48% for theophylline and budesonide, respectively. From these observations it can be concluded that budesonide and theophylline drug-loaded PLA nanoparticles are suitable drug delivery systems for combination therapy of asthma and COPD.

Original languageEnglish
Article number101128
JournalJournal of Drug Delivery Science and Technology
Volume53
DOIs
Publication statusPublished - 21 Jun 2019

Keywords

  • 16HBE14o-cells
  • Budesonide
  • Co-encapsulation
  • Franz diffusion cells
  • Nanoparticles
  • Poly(lactic acid)
  • Theophylline

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