Polymeric micelles have attracted much attention in recent years as nanocarriers for sustained drug delivery. While polymer micelles are often obtained by the self-assembly of amphiphilic block copolymers, unimolecular (covalently bonded) micellar structures have significant advantages as delivery vehicles due to their stable structure, insensitive to solvency conditions. The synthesis of biocompatible dendritic unimolecular micelles was accomplished by grafting poly(ethylene oxide) segments onto dendritic graft (arborescent) poly(γ-benzyl L-glutamate) (PBG) substrates. The dendritic substrates were synthesized by successive cycles of partial deprotection and grafting reactions of PBG chain segments. The coupling reactions were optimized through systematic variations in the reaction conditions. The encapsulation and release properties of these unimolecular micelles were investigated using doxorubicin (DOX) as a model hydrophobic anticancer drug, that was efficiently encapsulated via physical entrapment within the core of the arborescent poly(γ-benzyl L-glutamate)-g-poly(ethylene oxide) (PBG-g-PEO) micelles. Doxorubicin hydrochloride (DOX.HCl) was also loaded into hydrophilic arborescent poly(L-glutamic acid)-g-poly(ethylene oxide) (PGA-g-PEO) copolymers via electrostatic interactions. The drug-loaded unimolecular micelles exhibited pH-responsive drug release behavior, with a slower release rate at physiological pH (7.4) than at pH 5.5.

Unimolecular micelles based on arborescent polypeptides for sustained drug delivery

251st National Meeting (2016)

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