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已发表论文

Micelle-templated, poly(lactic-co -glycolic acid) nanoparticles for hydrophobic drug delivery

 

Authors Nabar GM, Mahajan KD, Calhoun MA, Duong AD, Souva MS, Xu J, Czeisler C, Puduvalli VK, Otero JJ, Wyslouzil BE, Winter JO

Received 24 May 2017

Accepted for publication 15 July 2017

Published 10 January 2018 Volume 2018:13 Pages 351—366

DOI https://doi.org/10.2147/IJN.S142079

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Professor Murali Yallapu

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster

Purpose: Poly(lactic-co -glycolic acid) (PLGA) is widely used for drug delivery because of its biocompatibility, ability to solubilize a wide variety of drugs, and tunable degradation. However, achieving sub-100 nm nanoparticles (NPs), as might be desired for delivery via the enhanced permeability and retention effect, is extremely difficult via typical top-down emulsion approaches.
Methods: Here, we present a bottom-up synthesis method yielding PLGA/block copolymer hybrids (ie, “PolyDots”), consisting of hydrophobic PLGA chains entrapped within self-assembling poly(styrene--ethylene oxide) (PS--PEO) micelles.
Results: PolyDots exhibit average diameters <50 nm and lower polydispersity than conventional PLGA NPs. Drug encapsulation efficiencies of PolyDots match conventional PLGA NPs (ie, ~30%) and are greater than those obtained from PS--PEO micelles (ie, ~7%). Increasing the PLGA:PS--PEO weight ratio alters the drug release mechanism from chain relaxation to erosion controlled. PolyDots are taken up by model glioma cells via endocytotic mechanisms within 24 hours, providing a potential means for delivery to cytoplasm. PolyDots can be lyophilized with minimal change in morphology and encapsulant functionality, and can be produced at scale using electrospray.
Conclusion: Encapsulation of PLGA within micelles provides a bottom-up route for the synthesis of sub-100 nm PLGA-based nanocarriers with enhanced stability and drug-loading capacity, and tunable drug release, suitable for potential clinical applications.
Keywords: PLGA, nanoparticles, micelles, drug delivery, hydrophobic drug, block copolymer, glioma, electrospray