[Show abstract][Hide abstract] ABSTRACT: Targeted drug delivery requires novel biodegradable, specific binding systems with longer circulation time. The aim of this study was to prepare biotinylated poly(lactic acid) (PLA) nanoparticles (NPs) which can meet regular requirements as well conjugate more biotins in the polymer to provide better binding with streptavidin. A biotin-graft-PLA was synthesized based on previously published biodegradable poly(ethylene glycol) (PEG)-graft-PLA, with one polymer molecule containing three PEG molecules. Newly synthesized biotin-graft-PLA had three biotins per polymer molecule, higher than the previous biotinylated PLA (≤1 biotin per polymer molecule). A PEG with a much lower molecular weight (MW ~1900) than the previous biotinylated PLA (PEG MW ≥ 3800), and thus more biocompatible, was used which supplied good nonspecific protein-resistant property compatible to PEG-graft-PLA, suggesting its possible longer stay in the bloodstream. Biotin-graft-PLA specifically bound to streptavidin and self-assembled into NPs, during which naproxen, a model small molecule (MW 230 Da) and hydrophobic drug, was encapsulated (encapsulation efficiency 51.88%). The naproxen-loaded NPs with particle size and zeta potential of 175 nm and -27.35 mV realized controlled release within 170 hours, comparable to previous studies. The biotin-graft-PLA NPs adhered approximately two-fold more on streptavidin film and on biotin film via a streptavidin arm both in static and dynamic conditions compared with PEG-graft-PLA NPs, the proven nonspecific protein-resistant NPs. The specific binding of biotin-graft-PLA NPs with streptavidin and with biotin using streptavidin arm, as well as its entrapment and controlled release for naproxen, suggest potential applications in targeted drug delivery.
International Journal of Nanomedicine 01/2012; 7:457-65. DOI:10.2147/IJN.S24011 · 4.20 Impact Factor
[Show abstract][Hide abstract] 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.
Journal of Biomedical Materials Research Part A 01/2008; 89(1):160-7. DOI:10.1002/jbm.a.31965 · 2.83 Impact Factor