Πέμπτη 28 Φεβρουαρίου 2019

Miktoarm star polymers nanocarrier: synthesis, characterisation, and in-vitro drug release study

Abstract

Conjugation of poly(ethylene glycol) (PEG) to poly(lactide-co-glycolide) (PLGA) renders the latter with enhanced biocompatibility and broader overall capability in biomedical application. Novel miktoarm star polymers comprising PLGA and PEG segments are of interest for their potential as drug carriers. Thus, a series of miktoarm star copolymers, PLGA-(mPEG)2, with different PLGA arm molecular weights and methoxy-PEG (mPEG) arm (2000 g/mol), were synthesised via a four-step reaction using carbodiimide chemistry with a low steric hindrance trifunctional linker aminoadipic acid (AAA) and characterised by proton nuclear magnetic resonance (1H NMR), fourier transform infrared (FTIR), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). Results show that the miktoarm star polymers PLGA17.0-AAA(mPEG)2 and PLGA43.4-AAA(mPEG)2 formed stable nanoparticles and PLGA4.6-AAA(mPEG)2 self-assembled into stable nanomicelles. Fluorescence spectroscopy showed that the critical micelle concentration of PLGA4.6-AAA(mPEG)2 was very low at 6.03 × 10−7 g/mL. Model drug ibuprofen encapsulated nanoparticles and nanomicelles had good drug loading, high encapsulation efficiency, narrow size distribution, and spherical morphology with negative surface charges. The mean particle size increased with increasing PLGA molecular weights, from 37.28 ± 1.03 to 151.5 ± 0.86 nm. In-vitro release of model drug ibuprofen over 7 days from PLGA43.4-AAA(mPEG)2 nanoparticles (61.65 ± 3.04%) was higher than those of PLGA4.6-AAA(mPEG)2 nanomicelles (26.93 ± 1.49%) and PLGA17.0-AAA(mPEG)2 nanoparticles (10.57 ± 0.29%), with all demonstrating controlled release characteristics. In conclusion, the novel miktoarm star polymers PLGA43.4-AAA(mPEG)2 and PLGA17.0-AAA(mPEG)2 and their nanoparticles, and PLGA4.6-AAA(mPEG)2 and its nanomicelles have a great potential as a nanocarrier for controlled delivery of hydrophobic drugs.



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