Abstract

Abstract

Abstract

A novel seven-arm star block copolymer poly(L-lactide-star block-N-isopropylacrylamide) (PLLA-sb-PNIPAAm), comprised of a hydrophobic poly(L-lactide) (PLLA) arm and an average of six hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) arms, was designed and synthesized. The amphiphilic PLLA-sb-PNIPAAm copolymer was capable of self-assembling into nano-sized micelle in water, which was confirmed by FT-IR, ¹H NMR and fluorescence spectroscopy. Transmission electron microscopy images showed that these nano-sized micelles were regularly spherical in shape. Micelle size determined by size analysis was around 100 nm in diameter. The micelles showed reversible dispersion/aggregation in response to temperature changes through an outer polymer shell of PNIPAAm at around 31°C, observed by optical absorbance measurements. The anticancer drug methotrexate (MTX) as model drug was loaded in the polymeric nano-sized micelles. In vitro release behavior of MTX was investigated, which showed a drastic thermoresponsive fast/slow switching behavior according to the temperature-responsive structural changes of a micellar shell structure. The reversible and sensitive thermoresponse of this micelle might provide opportunities to construct a novel drug delivery system in conjunction with localized hyperthermia. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007

Novel composite poly(N-isopropylacrylamide) (PNIPAAm) hydrogels, containing poly(N-isopropylacrylamide)-block-poly(methyl methacrylate) (PNIPAAm-b-PMMA) micelles for sustained drug delivery were prepared and characterized. Various amounts of thermal sensitive PNIPAAm-b-PMMA micelles were incorporated physically into thermosensitive PNIPAAm bulk hydrogel to form composite PNIPAAm hydrogels. The resultant composite hydrogels were characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) for morphological and thermal properties, respectively. The temperature dependence of swelling ratio and response kinetics upon heating or cooling were also investigated to understand the smart properties, that is, temperature-sensitive properties of the composite PNIPAAm hydrogels. These composite PNIPAAm hydrogels exhibited a faster shrinking kinetics than the one of pure PNIPAAm hydrogels. In addition, prednisone acetate, used as model drug, was loaded into the micelles incorporated to the composite PNIPAAm hydrogels. The controlled release behavior of the novel composite PNIPAAm hydrogels at different temperatures (22 and 37°C) was examined. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007

The well-defined, thermosensitive and biodegradable graft copolymers, poly(N-isopropylacrylamide)-b-[2-hydroxyethyl methacrylate-poly(ε-caprolactone)]_n (PNIPAAm-b-(HEMA-PCL)_n) (n = 3 or 9), were synthesized by combining reversible addition-fragmentation chain transfer polymerization and macromonomer method. The copolymers were able to self-assemble into micelles in water with low critical micellar concentration and demonstrated temperature sensitivity with a lower critical solution temperature at around 36 °C. Transmission electron microscopy shows that the micelles exhibit a nanosized spherical morphology within a size range of 30–100 nm. The PNIPAAm-b-(HEMA-PCL)₃ copolymer exhibited biodegradation and low cytotoxicity. The paclitaxel-loaded PNIPAAm-b-(HEMA-PCL)₃ micelles displayed thermosensitive controlled release behavior, which indicates potential as drug carriers. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5354–5364, 2007

Summary: A novel thermosensitive amphiphilic copolymer (PCL-g-P(NIPAAm-co-HEMA)) comprised of hydrophobic PCL segments and hydrophilic P(NIPAAm-co-HEMA) segments was designed and synthesized. The structure of the copolymer was characterized by FT-IR, ¹H NMR and GPC analysis. The copolymer may self-assemble into micelles in water and the resulting micelles demonstrated temperature sensitivity with a lower critical solution temperature (LCST) of 33 °C. The critical micellar concentration (CMC) obtained from surface tension measurements and the fluorescence method was around 30 mg · L⁻¹. Transmission electron microscopy (TEM) showed that the micelles exhibit a nanospheric morphology within a narrow size range of 150–160 nm. A cytotoxicity study showed that the PCL-g-P(NIPAAm-co-HEMA) copolymer exhibits good biocompatibility. The controlled drug release of the resulting micelles was investigated and it was found that micelles loaded with prednisone acetate showed improved drug release behavior due to the special micellar structure.

Summary: In this paper, unsaturated groups were introduced into poly(lactic acid) (PLA) for fabricating PLA-based nanospheres with carbon-carbon double bonds as functional groups. The morphology dependencies on fabrication conditions, including the fabrication time as well as the stirring rate, were also investigated.

Hydrophobic poly(lactic acid) nanospheres were fabricated and used as an additive during the polymerization and gelation process of temperature-sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The influence of hydrophobic additive on properties of PNIPAAm hydrogels was examined. The interior morphology studied by scanning electron microscopy revealed that the hydrophobic additive induced a macroporous structure in the resulting PNIPAAm hydrogels. Results demonstrate that the hydrophobic additive acts as a pore-forming agent like conventionally used hydrophilic additive does during the gelation process. Because of the macroporous network and incorporated additives, the temperature-sensitive characteristics, particularly the equilibrium swelling ratio at room temperature and shrinking rate upon temperature increase of modified PNIPAAm hydrogels, are significantly improved. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5490–5497, 2005