Polymeric nanoparticles for pulmonary protein and DNA delivery

Abstract

Polymeric nanoparticles (NPs) are promising carriers of biological agents to lung due to advantages including biocompatibility, ease of surface modification, localized action and reduced systemic toxicity. However, there have been no studies extensively characterizing and comparing the behavior of polymeric NPs for pulmonary protein/DNA delivery both in vitro and in vivo. We screened six polymeric NPs: gelatin, chitosan, alginate, poly lactic-co-glycolic acid (PLGA), PLGA-chitosan, and PLGA-polyethylene glycol (PEG), for inhalational protein/ DNA delivery. All NPs except PLGA-PEG and alginate were <300 nm in size with bi-phasic core compound release profile. Gelatin, PLGA NPs and PLGA-PEG NPs remained stable in deionized water, serum, saline and simulated lung fluid (Gamble’s solution) over 5 days. PLGA-based NPs and natural polymer NPs exhibited highest cytocompatibility and dose-dependent in vitro uptake respectively by human alveolar type-1 epithelial cells. Based on these profiles, gelatin and PLGA NPs were used to encapsulate a) plasmid DNA encoding yellow fluorescent protein (YFP) or b) rhodamine-conjugated erythropoietin (EPO) for inhalational delivery to rats. Following a single inhalation, widespread pulmonary EPO distribution persisted for up to 10 days while increasing YFP expression was observed for at least 7 days for both NPs. The overall results support both PLGA and gelatin NPs as promising carriers for pulmonary protein/DNA delivery.

Pulmonary delivered polymeric micelles – Pharmacokinetic evaluation and biodistribution studies

“…In this context, microparticles [14][15][16][17], liposomes [18][19][20], nanoparticles [21,22], PEG-lipid micelles [23] and nanocrystals [24] have been investigated, and some different nanocarriers have been used to achieve pulmonary sustained release [24][25][26][27][28].…”

Folate Functionalized PLGA Nanoparticles Loaded with Plasmid pVAX1-NH36: Mathematical Analysis of Release

“…pVAX1-NH36 loading in pDNA-NPs (DL) was determined by subtracting the amount of pVAX1-NH36 recovered in wash solutions from the initial amount of pDNA added [35,49,50]. Free pVAX1-NH36 concentration in all solutions was measured by HPLC-HIC [51] with a source 15PHE (Phenil-Polyestirene) column of 0.46 cm of diameter per 10 cm of length on an Akta purifier 10 UPC (GE Healthcare, Chicago, IL, USA).…”

Recent advances in topical delivery of proteins and peptides mediated by soft matter nanocarriers

“…PLGA and natural polymer based nanoparticles exhibited the highest biocompatibility and dose dependent accumulation in human alveolar type-1 epithelial cells. Following a single inhalation of rhodamine-labeled erythropoietin, widespread protein distribution persisted for up to 10 days (Menon et al, 2014). It has to be kept in mind that drug release from polymeric particulate drug delivery systems is usually controlled by diffusion through the polymer matrix and its degradation.…”