Development of a new poly(ethylene glycol)‐graft‐poly(D,L‐lactic acid) as potential drug carriers

Abstract

A new poly(ethylene glycol) (PEG)-modified poly(D,L-lactic acid) (PLA) was synthesized by grafting maleic anhydride onto PLA and subsequently amidating with O,O'-bis-(2-aminopropyl) polypropylene glycol-block-polyethylene oxide-block-polypropylene glycol (H2N-PEG-NH2, Mw: 600). Its structure was confirmed by FTIR, DSC, 1H NMR, GPC, and ninhydrin test. The polymer is more hydrophilic compared with PLA according to contact angle tests, and is degradable as determined from its pH and mass changes during degradation. The polymer shows a 62.7% decrease in BSA absorption compared with PLA when dried in air, and a 82.76% decrease when dried under 65% humidity, as measured by fluorospectrophotometry. The polymer promotes adhesion and proliferation of osteoblasts, determined by MTT assay. With this new polymer, spherical nanoscale aggregates encapsulated with or without hydrophilic dye are formed spontaneously in water, visualized by inverted microscope and AFM. The particle size is concentration dependent as confirmed by dynamic light scattering, and its critical micelle concentration was 1.124 microg/mL as determined by a fluorescence method. The good hydrophilicity, degradability, cellular compatibility, protein-resistance, self-aggregation, and reactivity of the polymer may lead to its potential applications in drug delivery.

Novel PEG-graft-PLA nanoparticles with the potential for encapsulation and controlled release of hydrophobic and hydrophilic medications in aqueous medium

“…In fact, we have previously demonstrated the BSA resistance of PEG-graft-PLA film compared with PLA film. 21 The good protein-resistant property of PEG-graft-PLA NPs may ensure its long circulation in the bloodstream. 21 The stability study disclosed that the NPs could be stable after administration in the body and diluted by blood or encountered with neutral (ie, pH 7.0) and basic tissue fluid, eg, intestinal fluid, but may aggregate in acidic fluid, especially in the gastric fluid.…”

“…21 Briefly, 20 and 5 mL of tetrahydrofuran (THF) were used to dissolve 6.12 g of O,O´-Bis-(2-aminopropyl) polypropylene glycol-block-polyethylene oxide-block-polypropylene glycol (H 2 N-PEG-NH 2 , Mw 1900 Da, Sigma, St Louis, MO) and 10.00 g of 10% maleic anhydride graft PLA (MPLA), prepared in our lab, 22 respectively. To MPLA, H 2 N-PEG-NH 2 was added dropwise at 50-55°C, followed by 1 more hour of stirring.…”

“…21 The fluorospectrophotometer was used with fluorescein 5-isothiocyanate conjugated bovine serum albumin (FITC-BSA) as model protein based on the fact that albumin is the dominant protein in human plasma when adsorbed on PLA. The encapsulation efficiency and in vitro release of insulin and naproxen…”

“…The results indicated the BSA-resistant property of PEG-graft-PLA NPs and possible longer circulation in the bloodstream. 21 …”

“…20 In our previous study, a PEG-graft-PLA with PEG of lower Mw (600 Da) self-assembled into NPs in water and showed good protein resistance and cellular compatibility in vitro. 21 In the current study, we hypothesized that PEG-graft-PLA could realize the delivery of both hydrophobic and hydrophilic medications via self-assembly in aqueous medium and form NPs with increased circulation time compared with particles of PLA alone, on account of its amiphiphility, charge, and graft structure. To test our hypothesis, PEG-graft-PLA with PEG of Mw 1900 Da was synthesized, followed by the critical micelle concentration (CMC) test.…”