Micro-molecular drugs have special advantages to cope with challenging diseases, however their structure, physical and chemical properties, stability, and pharmacodynamics have more requirements for the way they are delivered into the body. Carrier-based drug delivery systems can circumvent many limited factors of drug delivery and increase their bioavailability. In this context, stable drug nanocarriers of alkaline amino acids (arginine, Arg) modified conjugated linoleic acid-carboxymethyl chitosan (CLA-CMCS) conjugate were developed, which could generate supramolecular micelles to effectively encapsulate the tyrosinase inhibitor phenylethyl resorcinol (PR). The resulting CCA-NPs were spherical nanoparticles with a mean size around 175 nm. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and cellular uptake investigation demonstrated that the CCA-NPs were non-cytotoxic and had excellent cell transport ability. In addition, these CCA-NPs were able to effectively deliver PR and inhibited melanin formation to reduce pigmentation by enhancing cellular uptake. In conclusion, our research indicated that nanocarriers based on self-assembly amphiphilic polymers constituted a promising and effective drug delivery system in hyperpigmentation targeting.
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