| 학회 | 한국고분자학회 |
| 학술대회 | 2005년 가을 (10/13 ~ 10/14, 제주 ICC) |
| 권호 | 30권 2호 |
| 발표분야 | 의료용 고분자 부문위원회 |
| 제목 | Synthesis and Application of Thermosensitive Nanoparticles using Poly(N-isopropylacrylamide-b-ε-caprolactone) and Poly(ethylene glycol-b-ε-caprolactone) |
| 초록 | INTRODUCTION The polymeric micelles as drug carrier systems have been investigated to overcome the problems of conventional drug carriers.1 AB-type block copolymers are the most appropriate candidates of drug carriers because of small aggregation number and the micelle stability due to their simple molecular architecture. The polymeric micelles have been considered one of the promising candidates for drug delivery system owing more to the increment of drug concentration in an aqueous milieu than to the solubility limit of the hydrophobic free drug by partitioning the drugs into the hydrophobic core.2 The hydrophilic corona, mostly composed by poly(ethylene glycol) (PEG), endowed the polymeric micelles with escape from non-specific uptake by reticuloendothelial systems. The poly(N-isopropylacrylamide) (PNP) is a well-known water-soluble thermosensitive polymer showing reversible hydrated extended coil to globule transition by increasing temperature over the lower critical solution temperature (LCST).3 The PNP of thermosensitive micelles is water-soluble in an extended chain form below LCST. Above the LCST, it becomes hydrophobic and forms hydro-gel layer on surface of polymeric micelles. These polymeric micelles are expected to possess a high potential for sustained release of drug due to hydro-gel layer on surface of micelles. In this study, thermosensitive nanoparticles were prepared by self assembly of two different poly(ε-caprolactone) based block copolymers of poly(N-isopropylacrylamide)-b-poly(ε-caprolactone) (PNPCL) and poly(ethylene glycol)-b-poly(ε-caprolactone) (PEGCL). The hydrophobic block of PCL is well-known biodegradable polyester with excellent biocompatibility and degradability. The self-aggregation and thermosensitive behaviors of the mixed aggregates (with different PNPCL content) were investigated by using 1H NMR, turbidimetry, differential scanning microcalorimetry, dynamic light scattering, and fluorescence spectroscopy. EXPERIMENTAL METHOD Synthesis and characterization of PNP-OH, PNPCL and PEGCL diblock copolymers The PNP-OH was synthesized in methanol by temomerization of NIPAAm using ME as a chain transfer agent. PNPCL and PEGCL diblock copolymers were synthesized by ring opening polymerization of ε-caprolactone mPEG-OH and PNP-OH as initiators with trace amount of stannous octate (SnOct) as a catalyst. The polymerization was performed at 140 ℃ for 24h in xylene. After reaction, the copolymers were dissolved in dichloromethane and precipitated in an excess amount of diethyl ether and dried in vacuo for 48h. The synthesis of PNIPAAm-PCL and PEG-PCL diblock copolymers were confirmed by 1H-NMR and GPC. Preparation and characterization of thermosensitive nanoparticles Thermosensitive nanaparticles according to various ratios of PNPCL and PEGCL were prepared by a solvent evaporation method. The particle sizes and size distribution, morphology of nanoparticles, aggregation behavior in aqueous environment, and microscopic physicochemical properties of the aggregates were investigated by DLS, AFM, 1H NMR, and fluorescence spectroscopy, respectively. RESULT AND DISCUSSION The 1H NMR spectra and shifted chromatogram to higher MW range obtained by GPC of the copolymers clearly reveled that the block copolymers were successfully synthesized. The formed self-aggregates, with different compositions, showed different physicochemical properties such as particle size, LCST . The thermosensitive properties were critically affected by compositions of PNIPAAm block. The introduction of PNPCL into the self-aggregates endowed the unique characters, originated from thermosensitive PNIPAAm block, such as LCST, decrease of particle size by increasing temperature, and micropolarity changes. The particle size and CAC decreased with increment of PEPCL component due to increased PCL content and reduced bulky PNIPAAm block. The obtained aggregation numbers of PCL blocks in a hydrophobic microdomain, measured by fluorescence quenching method, were in the range of 7 ~ 14 with increasing the values by increasing PECL content. REFERENCES 1 Yokoyama M., et al., 1990, 11, 269. 2 Hubbell JA. et al., 2003, 300, 595. 3 Kohori F. et al., 2002, 78, 155. |
| 저자 | 최창용1, 채수영1, 권중근2, 조종수3, 나재운1 |
| 소속 | 1순천대, 2조선이공대, 3서울대 |
| 키워드 | Nanoparticles; Thermosensitivity |
