Drug solubilization by amino acid based polymeric nanoparticles: Characterization and biocompatibility studies

Abstract

Three novel amino acid based amphiphilic copolymers, poly(sodium N acryloyl-l-aminoacidate-co-dodecylacrylamide) (where aminoacidate=glycinate, leucinate, and phenylalaninate) were synthesized and characterized. These hydrophobically modified polyelectrolytes (HMPs) formed spheroidal nanoparticular aggregates above a critical aggregation concentration with average diameter 20–200nm and overall negative charges as indicated by dynamic light scattering (DLS) and zeta-potential (ζ≈−10.2 to −25.2) measurements, respectively. The size and shape of the nanostructures was confirmed by transmission electron microscopic images. The micropolarity and microviscosity of the nanosize aggregates were investigated by fluorescence probe method using extrinsic probes like N-phenyl-1-naphthylamine, pyrene, and 1,6-diphenyl-1,3,5-hexatriene. The stability of the copolymer micelles was investigated as a function of pH and temperature using fluorescence and DLS techniques. Both fluorescence probe and DLS data suggest that the copolymer micelles are highly stable under physiological condition (pH 7.4, 37.4°C). These HMP micelles were evaluated primarily as a drug delivery system. The ability of the copolymers to encapsulate hydrophobic drug was investigated using a poorly water-soluble antifungal drug, griseofulvin. Biocompability of the HMPs were examined by hemolytic and cytotoxicity assay. All three HMPs were non-hemolytic up to the tested concentration of about 1.0g/L. In vitro biological assay indicated that these new copolymers were also less toxic against 3T3 mammalian cell line. The studies suggest that these newly conceived amino acid based biocompatible polymeric nanoparticles might have potential application as injectible drug delivery systems which can enhance the therapeutic index of poorly water-soluble clinically challenging drugs.