Poly(aspartic acid)-block-polylactide diblock copolymers (PAsp-b-PLAs) having both hydrophilic and hydrophobic segments of various lengths were synthesized. These PAsp-b-PLA diblock copolymers formed polymeric micelles consisting of a hydrophobic PLA core and a hydrophilic, pH-sensitive PAsp shell in aqueous solution. The effects of the segment length of both the PLA and the PAsp portions and the pH of the solution on the shapes and sizes of the PAsp-b-PLA polymeric micelles were investigated. The results indicated a balance between the effects of electrostatic repulsion, hydrogen bonding in the PAsp shell layer, and hydrophobic interactions in the PLA core determine the sizes of the PAsp-b-PLA polymeric micelles. Moreover, the PAsp-b-PLA polymeric micelles did not possess any cytotoxic activity against L929 fibroblast cells. The obtained polymeric micelle should be useful for biodegradable biomedical materials such as drug delivery vehicle.

Summary: A poly(aspartic acid)‐block‐polylactide (PAsp‐block‐PLA) diblock copolymer was synthesized through the polymerization of β‐benzyl‐L‐aspartate‐N‐carboxyanhydride [Asp(OBzl)‐NCA] with amino‐terminating polylactide (NH2‐PLA) as a macroinitiator. The chain length of the PAsp segment could be easily controlled by changing the monomer/initiator ratio. Dynamic light scattering measurements of PAsp‐block‐PLA aqueous solutions revealed the formation of polymeric micelles. Changes in the micelles as a function of pH were investigated.The structure and formation of micelles of the poly(aspartic acid)‐block‐polylactide (PAsp‐block‐PLA) diblock copolymers synthesized here.imageThe structure and formation of micelles of the poly(aspartic acid)‐block‐polylactide (PAsp‐block‐PLA) diblock copolymers synthesized here.

The syntheses of amphiphilic AB‐type diblock copolymers composed of hydrophobic polylactide segment and hydrophilic polydepsipeptide segment with amino or carboxyl groups were performed. The protected cyclodepsipeptides cyclo[Glc‐Lys(Z)] and cyclo[Glc‐Asp(OBzl)] (where Glc is glycolic acid, Lys is lysine, Asp is aspartic acid, Z is benzyloxycarbonyl, and OBzl is benzyl) were first polymerized in tetrahydrofuran (THF) with potassium ethoxide as an initiator to obtain the corresponding protected polydepsipeptides. After the terminal hydroxyl groups of the protected polydepsipeptides were converted into the potassium alcoholates with K/naphthalene, L‐lactide was polymerized in the presence of the corresponding polymeric alcoholates as macroinitiators in THF to obtain poly[Glc‐Lys(Z)]‐block‐poly(L‐lactide) and poly[Glc‐Asp(OBzl)]‐block‐poly(L‐lactide). Subsequent deprotection of Z and OBzl groups gave the objective amphiphiles poly(Glc‐Lys)‐block‐poly(L‐lactide) and poly(Glc‐Asp)‐block‐poly(L‐lactide), respectively. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1218–1225, 2002

The synthesis of poly(L-lactide) (polyLA) end-capped with lactose residue was studied from the standpoint of development of a new bioabsorbable material. After the hydroxyl group of t-butoxycarbonyl(Boc)-aminoethanol was converted to Boc-aminoethanol-OK by using potassium/naphthalene, L-lactide was polymerized in tetrahydrofuran using Boc-aminoethanol-OK as an initiator at room temperature to prepare polyLA-NHBoc. Subsequently, the removal of the Boc group in terminal Boc-aminoethanol residue was performed by treatment of formic acid to obtain the amino group end-capped polyLA (polyLA-NH(2)) as a reactive polyLA derivative. The coupling reactions of lactose with polyLA-NH(2) were investigated by two methods; the synthetic method through reductive amination of lactose with polyLA-NH(2) in the presence of sodium cyanoborohydride as a reducing agent did not give high degree of substitution of end-capped lactose residue per polyLA molecule, whereas the synthetic method through the ester interchange reaction of lactonolactone with polyLA-NH(2) gave Lac-polyLA perfectly end-capped with lactose residue.

A novel hyaluronic acid (HA)-based hydrogel was prepared through polyion complex (PIC) formation between cationic polylactide (PLA)-based microspheres (MS+) and hyaluronic acid (HA-) as an anionic polyelectrolyte. The MS+ and HA formed a biodegradable PIC hydrogel (HA-/MS+) when mixed in aqueous media. The swelling behavior and mechanical properties of the PIC hydrogel could be controlled by changing the charge ratio between HA- and MS+. In addition, the HA-/MS+ PIC hydrogel resulted in a lower inflammatory response compared with a collagen hydrogel in vivo.