Double-Walled Poly-(D,L-lactide-co-glycolide) (PLGA) and Poly(L-lactide) (PLLA) Nanoparticles for the Sustained Release of Doxorubicin.

M Margarida Cardoso,Inês N Peca,Rui Gardner,Telma Lopes,A Bicho

doi:10.3390/polym13193230

M Margarida Cardoso, Inês N Peca + Show 3 more

Open Access

https://doi.org/10.3390/polym13193230

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Journal: Polymers	Publication Date: Sep 23, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: Instituto Gulbenkian de Ciência

Abstract

Double-walled nanoparticles (DWNPs), containing doxorubicin as a model drug, were produced using poly-(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by the solvent evaporation technique. Double-walled microparticles containing doxorubicin were also produced to make possible the examination of the inner morphology and drug distribution using optical and fluorescence microscopy. The produced microparticles present a double-walled structure with doxorubicin solubilized in the PLGA-rich phase. The DWNPs produced present very low initial burst values and a sustained DOX release for at least 90 days with release rates decreasing with the increase in the PLLA amount. Zero-order release kinetics were obtained after day 15. The results support that the PLLA layer acts as a rate control barrier and that the diffusion of doxorubicin from the drug-loaded inner PLGA core can be retarded by an increase in the thickness of the unloaded outer layer. The unloaded double-walled nanoparticles produced were used in in vitro tests with CHO cells and demonstrate that they are nontoxic, while the double-walled nanoparticles loaded with doxorubicin caused a great cellular viability and decreased when tested in vitro.

Highlights

The use of nanoparticles (NP) as drug carriers is one of the most promising areas of human health care science since they can circulate in the blood or cross cell membranes and be internalized [1,2,3,4,5,6]
Matsumoto and co-workers found that the phenomenon of polymer-polymer phase separation can be applied with the Poly(Llactide) (PLLA)/Poly(DL-lactide-co-glycolide) (PLGA) system [8], both biodegradable and biocompatible polymers that have generated tremendous interest [9,10]
Double-walled nanoparticles (DWNPs) made of PLGA and PLLA with PLLA/PLGA mass ratios of 2:1, 4:1 and 6:1 loaded with DOX were successfully prepared

Summary

Introduction

The use of nanoparticles (NP) as drug carriers is one of the most promising areas of human health care science since they can circulate in the blood or cross cell membranes and be internalized [1,2,3,4,5,6]. Most of the studies published so far were performed with a single-polymer layer NP where a high initial burst release generally occurs, which present a limitation in clinical application This restriction can be overcome using particles containing two immiscible polymers that form a core (internal) and a shell (outer) layer, commonly known as double-walled (DW) particles. The use of DW particles allows the drug release rate to be tuned by choosing the suitable core and shell polymers and adjusting the thickness of the outer layer by handling the polymers mass ratio. This approach provides more options concerning the type of drug release profiles intended for each type of treatment [7]. Studies using this system and copolymers of PLGA to produce double-walled microparticles (DWMP)

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