Polymer micellar aggregates of novel amphiphilic biodegradable graft copolymer composed of poly(aspartic acid) derivatives: Preparation, characterization, and effect of pH on aggregation

Novel amphiphilic biodegradable graft copolymer based on poly(aspartic acid) was prepared by attaching monomethoxy polyethylene glycol (mPEG) as hydrophiphic segment to poly(aspartic acid-g-octadecylamine) (PASP-g-ODA) as hydrophobic backbone. The chemical structures of amphiphilic copolymers were confirmed by FTIR and 1H NMR spectroscopy. The polymeric micelles were prepared with solvent evaporation and their physicochemical properties in aqueous media were characterized by dynamic light scattering (DLS) and fluorescence spectroscopy. These micelles were confirmed to be pH-sensitive by measuring optical transmittance of micelle solution and the size of micellar aggregates. The number average diameter of polymeric micelles prepared in medium at pH 2.5 was larger than that in neutral and basic medium and showed a bimodal size distribution because of the protonation of carboxyl groups in backbone. Furthermore, the polymeric micelle can load water-insoluble drug (podophyllotoxin), and the drug release from micelles showed a pH-dependency. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006

[1]  E. Kokufuta,et al.  On the Poly(beta-DL-aspartic acid) , 1980 .

[2]  Y. Bae,et al.  Sulfonamide based pH-sensitive polymeric micelles: physicochemical characteristics and pH-dependent aggregation , 2003 .

[3]  E. Neuse,et al.  Water soluble polyamides as potential drug carriers. IX. Polyaspartamides grafted with amine-terminated poly(ethylene oxide) chains , 1997 .

[4]  P. Neri,et al.  Synthesis of alpha beta-poly((2-hydroxyethyl)-DL-aspartamide), a new plasma expander. , 1973, Journal of medicinal chemistry.

[5]  M. Francis,et al.  Solubilization of poorly water soluble drugs in micelles of hydrophobically modified hydroxypropylcellulose copolymers. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[6]  John Samuel,et al.  Poly(ethylene oxide)-block-poly(L-amino acid) micelles for drug delivery. , 2002, Advanced drug delivery reviews.

[7]  J. Nah,et al.  Clonazepam release from core‐shell type nanoparticles composed of poly(γ‐benzyl L‐glutamate) as the hydrophobic part and poly(ethylene oxide) as the hydrophilic part , 1998 .

[8]  D. Lasič.  Mixed micelles in drug delivery , 1992, Nature.

[9]  K. Kataoka,et al.  Physicochemical properties and nuclease resistance of antisense-oligodeoxynucleotides entrapped in the core of polyion complex micelles composed of poly(ethylene glycol)-poly(L-lysine) block copolymers. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[10]  C. Chu,et al.  Novel biodegradable copolymers containing pendant amine functional groups based on aspartic acid and poly(ethylene glycol) , 1998 .

[11]  Sung‐Ho Kim,et al.  Development of a polymeric nanoparticulate drug delivery system. In vitro characterization of nanoparticles based on sugar-containing conjugates. , 2002, International journal of pharmaceutics.

[12]  M. Malmsten,et al.  Self-assembly in aqueous block copolymer solutions , 1992 .

[13]  A. Wartburg,et al.  The chemical and biological route from podophyllotoxin glucoside to etoposide: ninth Cain memorial Award lecture. , 1991 .

[14]  K. Kataoka,et al.  Novel polyion complex micelles entrapping enzyme molecules in the core: Preparation of narrowly-distributed micelles from lysozyme and poly(ethylene glycol)-poly(aspartic acid) block copolymer in aqueous medium , 1998 .

[15]  T. Okano,et al.  Characterization of physical entrapment and chemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery to a solid tumor. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[16]  Jong-Duk Kim,et al.  Self-aggregates of poly(2-hydroxyethyl aspartamide) copolymers loaded with methotrexate by physical and chemical entrapments. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[17]  Y. Nagasaki,et al.  Preparation and characterization of polymer micelles from poly(ethylene glycol)-poly(D,L-lactide) block copolymers as potential drug carrier. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[18]  D. Sackett.  Podophyllotoxin, steganacin and combretastatin: natural products that bind at the colchicine site of tubulin. , 1993, Pharmacology & therapeutics.

[19]  E. Greenspan,et al.  Response of patients with advanced neoplasms to the intravenous administration of alpha-peltatin. , 1954, Journal of the National Cancer Institute.