Chitosan-N-poly(ethylene glycol) brush copolymers: Synthesis and adsorption on silica surface

Chitosan-N-poly(ethylene glycol) brush copolymers with different degree of substitution (DS) were synthesized via reductive amination of chitosan by methoxy poly(ethylene glycol) (MPEG) aldehyde. Chitosan-N-MPEG copolymers were high-molecular-weight products with desirable DS; solubility and solution viscosity of those copolymers depended on the method of the synthesis of MPEG aldehyde and on DS. Synthesis of MPEG aldehyde by the use of TEMPO radical/BAIB was not suitable because of partial oxidation of methoxy groups of MPEG resulting in bifunctional PEG derivatives leading to cross-linking. Adsorption studies of chitosan-N-MPEG graft copolymers on silica surface show that these polymers adsorb in highly hydrated layers.     

Preparation, characterization and enzyme inhibition of methylmethacrylate copolymer nanoparticles with different hydrophilic polymeric chains

Methylmethacrylate copolymer nanoparticles with different hydrophilic chains were prepared by the free radical polymerization of methylmethacrylate with N-isopropylacrylamide (NIPAAm), N-methacrylic acid (MAA), N-trimethylaminoethylmethacrylate chloride (TMAEMC) or N-dimethylaminoethylmethacrylate hydrochloride (DMAEMC). These particles were characterized by particle size and zeta potential. The polymerization conditions were shown to influence the particle size and surface charge. Particle sizes of MMA-NIPAAm nanoparticles after 3 h of reaction reached constant level at 180 nm. An increasing amount of total monomer (0.5-5%) would result in the nanoparticles of particle size of 115-204 nm for 30% NIPAAm of the total monomer. In the same range of 5-40% NIPAAm of the total monomer, the particle size decreased from 280 to 170 nm. The concentration of the initiator APS up to a concentration of 0.2% for MMA-TMAEMC and 0.1% for MMA-NIPAAm showed no effect on the particle size of the final nanoparticle suspensions, while higher concentration would lead to aggregation in the polymerization process. MMA-NIPAAm nanoparticles were pH-dependent in zeta potential at pH 1-12 values reducing from 12.2 mV to −16.8 mV, respectively. Nanoparticles were incubated with pepsin and trypsin at 37 °C for 20 min and their enzyme inhibition was determined. The activity of pepsin decreased to 27% in the presence of MMA-NIPAAm nanoparticles, and MMA-MAA nanoparticles reduced the activity of trypsin to 39%, respectively.     

Self-assembly of poly(ethylene glycol)-block-polypyridine copolymer into micelles and at silica surface: effect of molecular architecture on silica dispersion

We have newly synthesized amphiphilic block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic pyridine segments (PEG-b-Py). Chain transfer agent-terminated PEG was subsequently chain-extended with 3-(4-pyridyl)-propyl acrylate to obtain PEG-b-Py by reversible additional-fragmentation chain transfer polymerization. Particularly, the effect of varying molecular weight (Mn) of PEG (Mn?=?2,000 and 5,000) and Py in the block copolymers was investigated in terms of critical micelle concentration, pyrene solubilization, micelle size distribution, and association number per micelle. Based on the amphiphilic balance, PEG-b-Pys formed core-shell type polymer micelle. The association number of PEG2k-b-Py was higher than that of PEG5k-b-Py, suggesting the degree of phase separation strongly depended on PEG Mn. Furthermore, the adsorption of PEG-b-Py copolymer onto silica nanoparticles as dispersant was studied to estimate the effect of PEG Mn in the copolymers and their solubility in the medium on the adsorption. Adsorbed density of PEG2k-b-Py copolymer onto silica nanoparticle was higher than that of PEG5k-b-Py, which was significantly correlated with the degree of phase separation. Furthermore, the adsorbed amount of copolymer increased with the increase in ionic strength due to the reduced solubility of PEG in the buffer solution. The resultant dispersion stability was highly correlated with the graft density of copolymer onto silica surface. However, the stability of PEG2k-b-Py coated particles was lower than that with PEG5k-b-Py, this is attributed to the relatively thin layer of PEG at the silica surface, which cannot provide the system with sufficient steric stabilization as the salt concentration increases. These fundamental investigations for the surface modification of the nanoparticle provide the insight into the highly stable colloidal dispersion, particularly in the physiological condition with high ionic strength.     

Biopolymeric delivery system for controlled release of polyphenolic antioxidants

A chitosan based delivery system has been developed for the controlled release of polyphenolic antioxidants such as catechin. Placebo and catechin entrapped particulate delivery systems were prepared using the sodium tripolyphosphate ionic crosslinking technique. The particles have been characterised by transmission electron microscopy, particle size and charge distribution analysis, Fourier Transform infrared spectroscopy, differential scanning calorimetry and entrapment efficiency studies. These studies gave an understanding of the physico-chemical interactions that influence the biopolymer during particle formation and entrapment of catechin. The in vitro release of catechin was carried out in enzyme-free simulated gastric and intestinal fluids. Although nanoparticles could be formed by the crosslinking technique used, there was aggregation behaviour observed after retrieval and freeze-drying of the particles as shown by transmission electron microscopy. Both the placebo and catechin-loaded particles had mean particle size range of about 4.27-6.29 μm after freeze-drying and were charged. Fourier Transform infrared spectroscopy, differential scanning calorimetry studies indicated minor structural interactions between catechin and chitosan matrix. Entrapment efficiency of the particles ranged between 27% and 40%. In vitro release studies indicated that the release of catechin in simulated gastric and intestinal fluids was between 15% and 40%, depending on the structural interactions between catechin and the chitosan matrix.     

Novel pentablock copolymer (PLA–PCL–PEG–PCL–PLA)-based nanoparticles for controlled drug delivery: effect of copolymer compositions on the crystallinity of copolymers and in vitro drug release profile from nanoparticles

The purpose of this investigation was to design novel pentablock copolymers (polylactide–polycaprolactone–polyethylene glycol–polycaprolactone–polylactide) (PLA–PCL–PEG–PCL–PLA) to prepare nanoparticle formulations which provide continuous delivery of steroids over a longer duration with minimal burst effect. Another purpose was to evaluate the effect of poly(l-lactide) (PLLA) and poly(d,l-lactide) (PDLLA) incorporation on crystallinity of pentablock copolymers and in vitro release profile of triamcinolone acetonide (selected as model drug) from nanoparticles. PLA–PCL–PEG–PCL–PLA copolymers with different block ratio of PCL/PLA segment were synthesized. Release of triamcinolone acetonide from nanoparticles was significantly affected by crystallinity of the copolymers. Burst release of triamcinolone acetonide from nanoparticles was significantly minimized with incorporation of proper ratio of PDLLA in the existing triblock (PCL–PEG–PCL) copolymer. Moreover, pentablock copolymer-based nanoparticles exhibited continuous release of triamcinolone acetonide. Pentablock copolymer-based nanoparticles can be utilized to achieve continuous near–zero-order delivery of corticosteroids from nanoparticles without any burst effect.     

Synthesis and antifungal property of N-(aryl) and quaternary N-(aryl) chitosan derivatives against Botrytis cinerea

A series of N-(aryl) and their quaternary N-(aryl) chitosan derivatives were synthesized and evaluated for their antifungal activity against crop-threatening fungus Botrytis cinerea. Schiff bases were firstly synthesized by the reaction of chitosan with cinnamaldehyde, cuminaldehyde and 4-dimethylaminobenzaldehyde followed by reduction with sodium borohydride to form N-(aryl) chitosans. Quaternary N-(aryl) chitosans were then obtained by reaction of N-(aryl) chitosan compounds with ethyl iodide. The chemical structures were characterized by ¹H-NMR, FT-IR and UV spectroscopic techniques. The antifungal activity was evaluated in vitro against B. cinerea by mycelial growth inhibition method and in vivo by application of compounds to tomato plants prior to inoculation with fungal spores. In an in vitro experiment, all quaternized chitosans were more active than N-(aryl) chitosan derivatives and N,N,N-(diethylcinnamyl) chitosan (QC1) was the most potent (EC₅₀ = 1,147 mg/L) against mecelia however, N,N,N-(diethyl-p-dimethylaminobenzyl) chitosan (QC3) was the most potent (EC₅₀ = 334 mg/L) against spores. In an in vivo study, no disease incidence (0.0 %) was observed with QC1 and QC3 at 1,000 mg/L. Spray liquid chitosan enhanced total phenolics and guaiacol peroxidase in inoculated leaves.     

Production of nanoparticles of methyl methacrylate and butyl methacrylate copolymers by microemulsion polymerization in the presence of maleic acid terminated poly(N-acetylethylenimine) macromonomers as cosurfactant

In this study, MMA/BMA copolymer nanoparticles were synthesized in oil-in-water microemulsions that were stabilized by sodium dodecyl sulphate (SDS) and initiated by potassium persulphate KPS. Maleic acid terminated poly(N-acetylethylenimine) (PNAEI) with two different chain lengths was also included in the recipe, as a cosurfactant and a comonomer. FTIR and ¹H-NMR proved incorporation of the macromonomer in the structure. High polymerization yields were achieved upto 98%. The viscosity average molecular weights of the copolymers were in the range of 2.77-5.50 × 10⁵. The glass transition temperatures of these copolymers were between 50.0 and 63.9 °C. The average diameter of nanoparticles were in range of 40-96 nm. It was possible to produce nanoparticles smaller than 100 nm and with narrower size distributions by using much lower concentrations of SDS by including the macromonomers in the microemulsion polymerization recipe.     

Synthesis and phase separation of amine-functional temperature responsive copolymers based on poly(N-isopropylacrylamide)

Free radical copolymerizations of N-isopropyl acrylamide (NIPAM) and cationic N-(3-aminopropyl) methacrylamide hydrochloride (APMH) were investigated to prepare amine-functional temperature responsive copolymers. The reactivity ratios for NIPAM and APMH were evaluated in media of different ionic strength (r_NIPAM = 0.7 and r_APMH = 0.7-1.2). Phase separation behavior of the random copolymers with only 5 mol% of the APMH was found to be suppressed in pure water at temperatures up to 45 °C due to electrostatic repulsion among the cationic amine groups randomly distributed along the copolymer chain. Alternate sequential addition of PNIPAM/APMH mixtures and pure NIPAM was used to provide increased control of the location of APMH units along the chain. Consequently (close to) homo-PNIPAM block(s) were formed as evidenced by its characteristic phase transition at 33 °C. The influences of the monomer feeding time and feeding interval time to the APMH distribution were investigated to prepare copolymers with thermo-induced phase separation under physiologically relevant temperature and to determine the extent of conjugation to poly(ethylene oxide).     

From well‐defined diblock copolymers prepared by a versatile atom transfer radical polymerization method to supramolecular assemblies

The synthesis of well‐defined diblock copolymers by atom transfer radical polymerization (ATRP) was explored in detail for the development of new colloidal carriers. The ATRP technique allowed the preparation of diblock copolymers of poly(ethylene glycol) (PEG) (number‐average molecular weight: 2000) and ionic or nonionizable hydrophobic segments. Using monofunctionalized PEG macroinitiator, ionizable and hydrophobic monomers were polymerized to obtain the diblock copolymers. This polymerization method provided good control over molecular weights and molecular weight distributions, with monomer conversions as high as 98%. Moreover, the copolymerization of hydrophobic and ionizable monomers using the PEG macroinitiator made it possible to modulate the physicochemical properties of the resulting polymers in solution. Depending on the length and nature of the hydrophobic segment, the nonionic copolymers could self‐assemble in water into nanoparticles or polymeric micelles. For example, the copolymers having a short hydrophobic block (5 < degree of polymerization < 9) formed polymeric micelles in aqueous solution, with an apparent critical association concentration between 2 and 20 mg/L. The interchain association of PEG‐based polymethacrylic acid derivatives was found to be pH‐dependent and occurred at low pH. The amphiphilic and nonionic copolymers could be suitable for the solubilization and delivery of water‐insoluble drugs, whereas the ionic diblock copolymers offer promising characteristics for the delivery of electrostatically charged compounds (e.g., DNA) through the formation of polyion complex micelles. Thus, ATRP represents a promising technique for the design of new multiblock copolymers in drug delivery. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3861–3874, 2001     

Synthesis and characterization of thermo-responsive copolymeric nanoparticles of poly(methyl methacrylate-co-N-vinylcaprolactam)

Copolymeric nanoparticles of methyl methacrylate (MMA) and N-vinylcaprolactam (VCL) were prepared through free radical polymerization using hydrogen peroxide and l-ascorbic acid as a redox initiator in o/w microemulsion containing sodium dodecyl sulphate (SDS). The copolymers were characterized by FTIR and gel permeation chromatography (GPC) and composition of copolymer was determined by ¹H NMR spectroscopy. Reactivity ratio was determined by linear least square and non-linear least square methods. The morphology and particle size distribution of copolymer latexes was determined through transmission electron microscopy (TEM) and dynamic light scattering (DLS). Copolymers were of less than 50 nm size with spherical morphology and latexes were stable for more than 6 months. Phase transition temperature measured through UV-vis spectrometry, for the synthesized copolymer indicates their potential use in biosensors and targeted drug delivery system. Cytotoxicity of nanoparticles was determined by MTT assay on B16F10 melanoma cell lines. Cell viability data shows the IC₅₀ values of copolymeric nanoparticles to be in the range of 0.01-0.1 mg/mL.     

Formulation of Quaternized Aminated Chitosan Nanoparticles for Efficient Encapsulation and Slow Release of Curcumin

An effective drug nanocarrier was developed on the basis of a quaternized aminated chitosan (Q-AmCs) derivative for the efficient encapsulation and slow release of the curcumin (Cur)-drug. A simple ionic gelation method was conducted to formulate Q-AmCs nanoparticles (NPs), using different ratios of sodium tripolyphosphate (TPP) as an ionic crosslinker. Various characterization tools were employed to investigate the structure, surface morphology, and thermal properties of the formulated nanoparticles. The formulated Q-AmCs NPs displayed a smaller particle size of 162 ± 9.10 nm, and higher surface positive charges, with a maximum potential of +48.3 mV, compared to native aminated chitosan (AmCs) NPs (231 ± 7.14 nm, +32.8 mV). The Cur-drug encapsulation efficiency was greatly improved and reached a maximum value of 94.4 ± 0.91%, compared to 75.0 ± 1.13% for AmCs NPs. Moreover, the in vitro Cur-release profile was investigated under the conditions of simulated gastric fluid [SGF; pH 1.2] and simulated colon fluid [SCF; pH 7.4]. For Q-AmCs NPs, the Cur-release rate was meaningfully decreased, and recorded a cumulative release value of 54.0% at pH 7.4, compared to 73.0% for AmCs NPs. The formulated nanoparticles exhibited acceptable biocompatibility and biodegradability. These findings emphasize that Q-AmCs NPs have an outstanding potential for the delivery and slow release of anticancer drugs.     

Preparation of a thermo- and pH-sensitive nanofibrous scaffold with embedded chitosan-based nanoparticles and its evaluation as a drug carrier

Environmentally sensitive poly(N-isopropylacrylamide) (PNIPAAm) nanofibrous scaffolds loaded with a hydrophilic drug were fabricated via an electrospinning process. First, thermally crosslinkable poly(NIPAAm-co-N-methylolacrylamide) (PNN) was synthesized by redox polymerization below the phase transition temperature of PNIPAAm. The phase transition temperature of the PNN copolymer could be altered from 34 to 40 °C by changing the ratio of N-methylolacrylamide (NMA) to NIPAAm. Subsequently, PNN/chitosan nanofibers were electrospun using ethanol/acetic acid/water as a cosolvent. The PNN/chitosan nanofibers were sensitive to both pH and temperature. The fibrous structure of the soaked PNN/chitosan nanofibers was successfully preserved by the crosslinking of NMA. Furthermore, the chitosan-based nanoparticles (NPs) were introduced into the PNN nanofibers (PNN/NPs) to achieve prolonged drug release. The nanoparticles were observed in the PNN nanofibers by transmission electron microscopy. All of the scaffolds examined had high tensile strengths (1.45 MPa or above) and exhibited no significant cytotoxicity toward human fetal skin fibroblasts. Finally, doxycycline hyclate was used as a model drug. The results illustrated that PNN/NPs nanofibrous scaffolds exhibited continuous drug release behavior for up to 1 week, depending on the pH and temperature.     

Synthesis of poly(ethylene glycol)/polypeptide/poly(D,L‐lactide) copolymers and their nanoparticles

Core‐shell structured nanoparticles of poly(ethylene glycol) (PEG)/polypeptide/poly(D ,L ‐lactide) (PLA) copolymers were prepared and their properties were investigated. The copolymers had a poly(L ‐serine) or poly(L ‐phenylalanine) block as a linker between a hydrophilic PEG and a hydrophobic PLA unit. They formed core‐shell structured nanoparticles, where the polypeptide block resided at the interface between a hydrophilic PEG shell and a hydrophobic PLA core. In the synthesis, poly(ethylene glycol)‐b‐poly(L ‐serine) (PEG‐PSER) was prepared by ring opening polymerization of N‐carboxyanhydride of O‐(tert‐butyl)‐L ‐serine and subsequent removal of tert‐butyl groups. Poly(ethylene glycol)‐b‐poly(L ‐phenylalanine) (PEG‐PPA) was obtained by ring opening polymerization of N‐carboxyanhydride of L ‐phenylalanine. Methoxy‐poly(ethylene glycol)‐amine with a MW of 5000 was used as an initiator for both polymerizations. The polymerization of D ,L ‐lactide by initiation with PEG‐PSER and PEG‐PPA produced a comb‐like copolymer, poly(ethylene glycol)‐b‐[poly(L ‐serine)‐g‐poly(D ,L ‐lactide)] (PEG‐PSER‐PLA) and a linear copolymer, poly(ethylene glycol)‐b‐poly(L ‐phenylalanine)‐b‐poly(D ,L ‐lactide) (PEG‐PPA‐PLA), respectively. The nanoparticles obtained from PEG‐PPA‐PLA showed a negative zeta potential value of ?16.6 mV, while those of PEG‐PSER‐PLA exhibited a positive value of about 19.3 mV. In pH 7.0 phosphate buffer solution at 36 °C, the nanoparticles of PEG/polypeptide/PLA copolymers showed much better stability than those of a linear PEG‐PLA copolymer having a comparable molecular weight. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis and properties of monocleavable amphiphilic comblike copolymers with alternating PEG and PCL grafts

Symmetric reduction‐responsive amphiphilic comblike copolymers mid‐disulfide‐functionalized comblike copolymers with alternating copolymer comprised of styrenic unit and N‐(2‐hydroxyethyl) maleimide (HEMI) unit (poly(St‐alt‐HEMI)) backbones and alternating PEG and PCL side chains (S‐CP(PEG‐alt‐PCL)) with poly(St‐alt‐HEMI) backbones and alternating poly(ε‐caprolactone) (PCL) and poly(ethylene glycol) (PEG) side chains were synthesized and used as nanocarriers for in vitro release of doxorubicin. The target copolymers with predetermined molecular weight and narrow molecular weight distribution (M_w/M_n = 1.15–1.20) were synthesized by reversible addition‐fragmentation chain transfer (RAFT) copolymerization of vinylbenzyl‐terminated PEG and N‐(2‐hydroxyethyl) maleimide mediated by a disulfide‐functionalized RAFT agent S‐CPDB, and followed by ring‐opening polymerization of ε‐caprolactone. When compared with linear block copolymer comprised of poly(ethylene glycol) (PEG) and poly(?‐caprolactone) (PCL) segments (PEG‐b‐PCL) copolymers, comblike copolymers with similar PCL contents usually exhibited decreased crystallization temperature, melting temperature, and degree of crystallinity, indicating the significant influence of copolymer architecture on physicochemical properties. Dynamic light scattering measurements revealed that comblike copolymers were liable to self‐assemble into aggregates involving vesicles and micelles with average diameter in the range of 56–226 nm and particle size distribution ranging between 0.07 and 0.20. In contrast to linear copolymer aggregates, comblike copolymer aggregates with similar compositions were of improved storage stability and enhanced drug‐loading efficiency. In vitro drug release confirmed the disulfide‐linked comblike copolymer aggregates could rapidly release the encapsulated drug when triggered by 10 mM DL ‐dithiothreitol. These reduction‐sensitive, biocompatible, and biodegradable aggregates have a potential as controlled delivery vehicles. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

PLA/PEG/PLA三嵌段共聚物载药纳米胶囊的制备及表征

用于药物控释体系的微胶束具有实心微球结构,药物分子主要吸附于微球表面,极易脱落,在释药初期有明显的突释效应;而微胶囊的药物主要集中于囊心部分,药物通过扩散作用以及高分子膜的降解而逐渐释放到环境中,因而更有利于药物分子平稳、缓慢地释放．对于自然界中能够自发形成微胶囊的小分子材料,其分子中往往具有一个较小的亲水部分和一个相对较大的憎水部分,     

Living radical polymerisation in heterogeneous conditions—suspension polymerisation

Transition metal mediated living radical polymerisation of butyl methacrylate has been demonstrated with a copper(I) halide N-alkyl-2-pyridylmethanimine ligands based catalyst. Optimum conditions were found to be with copper(I) chloride and N-octyl-2-pyridylmethanimine catalyst at 65 °C where conversions of 85% were achieved with polymers of M_n = 8900 g mol⁻¹ (theoretical = 8400 g mol⁻¹) and PDI = 1.23. Both non-ionic and ionic surfactants were employed which were also made by living radical polymerisation. The non-ionic surfactant was a block copolymer of PMMA from a polyethyleneglycol macroinitiator (total M_n = 7600 g mol⁻¹, PDI = 1.20) and the ionic surfactant PDMEAMA-PMMA (total M_n = 8000 g mol⁻¹, PDI = 1.21) with the PDMEAMA block quaternized with MeI (13.8%, 28.4%, 47.7% and 100%). A range of ligands were employed in the suspension polymerisation by varying the alkyl group on the ligand increasing the hydrophobicity (alkyl = propyl (PrMI), pentyl (PMI), octyl (OMI), dodecyl (DMI) and octadecyl (ODMI)). The more hydrophobic ligands were found to be more effective due to lower partitioning into the aqueous phase. Block copolymers of P(EMA)-P(BMA) and P(MMA)-P(BMA) were prepared by first preparing macroinitiators via living radical polymerisation (M_n = 1600 g mol⁻¹ (PDI = 1.23) for P(EMA) and M_n = 1500 g mol⁻¹ (PDI = 1.22) for P(MMA)) and using them for initiation of BMA in suspension polymerisation. Block copolymers had M_n between 12,800 and 13,700 g mol⁻¹ with PDI between 1.33 and 1.54. Block copolymer growth showed excellent linear first order kinetics wrt monomer and demonstrated characteristics expected of a living radical polymerisation. Particle sizes were measured by SEM and DLS with good agreement (1.4-2.8 μm) and SEM showed spherical particles were formed.     

Phase behavior of biodegradable amphiphilic poly(l,l-lactide)-b-poly(ethylene glycol)-b-poly(l,l-lactide)

This study describes the miscibility phase behavior in two series of biodegradable triblock copolymers, poly(l-lactide)-block-poly(ethylene glycol)-block-poly(l-lactide) (PLLA-PEG-PLLA), prepared from two di-hydroxy-terminated PEG prepolymers (M_n = 4000 or 600 g mol⁻¹) with different lengths of poly(l-lactide) segments (polymerization degree, DP = 1.2-145.6). The prepared block copolymers presented wide range of molecular weights (800-25,000 g mol⁻¹) and compositions (16-80 wt.% of PEG). The copolymer multiphases coexistance and interaction were evaluated by DSC and TGA. The copolymers presented a dual stage thermal degradation and decreased thermal stability compared to PEG homopolymers. In addition, DSC analyses allowed the observation of multiphase separation; the melting temperature, T_m, of PLLA and PEG phases depended on the relative segment lengths and the only observed glass transition temperature (T_g) in copolymers indicated miscibility in the amorphous phase.     

Methoxy poly(ethylene glycol)-b-poly(valerolactone) diblock polymeric micelles for enhanced encapsulation and protection of camptothecin

Amphiphilic block copolymers, methoxy poly(ethylene glycol)-b-poly(valerolactone) (mPEG-b-PVL), were synthesized via ring opening polymerization of δ-valerolactone in the presence of methoxy poly(ethylene glycol) (mPEG). The copolymers form micelle-like nanoparticles by their amphiphilic characteristics and their structures were examined by Nuclear Magnetic Resonance (NMR). The sizes of nanoparticles ranged from 60 to 120 nm as measured by dynamic light scattering detection, and were larger with higher molecular weight of the copolymers. The Critical Micelle Concentration (CMC) of these nanoparticles in water decreased with increasing molecular weight of hydrophobic segment. Stability analysis showed that the micellar solutions maintain their sizes at 37 °C for six weeks without aggregation or dissociation. The lyophilization method was better than the evaporation method when camptothecin (CPT) was incorporated to the micelles. The former method yielded higher CPT loading efficiency and lower aggregation. The loading efficiency of CPT could be more than 96% and a steady release rate of CPT was kept for twenty six days. Moreover, the mPEG-b-PVL polymeric micelles offered good protection of CPT lactone form at 37 °C for sixteen days. The copolymers showed no cytotoxicity towards L929 mouse muscular cells when incubated for one day. Taken together, the mPEG-b-PVL copolymer has potential to be used for the delivery of CPT or other similar drugs.     

A water-soluble PPDO/PEG alternating multiblock copolymer: Synthesis, characterization, and its gel-sol transition behavior

Biodegradable and nontoxic alternating multiblock copolymers based on poly (p-dioxanone) (PPDO) and poly (ethylene glycol) (PEG) were synthesized by the coupling reaction of two bifunctional prepolymers, a dihydroxyl-terminated PPDO and dicarboxylated PEG. The prepolymers and the resulting PPDO/PEG multiblock copolymers were characterized by various analytical techniques such as FT-IR, ¹H NMR, GPC, DSC and TG. At high concentration levels above critical gelation concentration (CGC), the aqueous solution of copolymers formed a gel. Temperature-sensitive gel to sol transition behaviors were investigated by the test tube inverting method. Dynamic light scattering (DLS) was used to investigate the micelle of copolymers, whose association probably caused the gelation of the system. Therefore, this novel copolymer has a great potential in injectable drug-delivery system for long-term delivery of drugs.     

Novel approaches for the preparation of silica-based zwitterionic hybrid copolymers

Two novel routes for the preparation of silica-based zwitterionic hybrid copolymers were proposed. A series of zwitterionic hybrid copolymers were prepared by the sulfonation of phenyl groups and the quaternary amination of tertiary amine groups alternately. Both FT-IR and ¹H NMR spectra confirm the step products. TGA and DrTGA analyses indicate that the thermal stability of these zwitterionic hybrid copolymers is higher than 400 °C. The determination of sulfonation degree reveals that the zwitterionic hybrid copolymer (c) from sulfonation-quarteramination (Route I) has the minimal value; meanwhile the anion-exchange capacity exhibits that the zwitterionic hybrid copolymer (e) from quarteramination-sulfonation (Route II) has the minimal value. These findings demonstrate the impact of electrostatic effect on the charge content of ionic groups. MALDI-TOF mass spectra exhibit that the decrease in the stability of the charged hybrid copolymers can be ascribed to the electrostatic effect between the molecular chains. The surface SEM images demonstrate that the surface of zwitterionic hybrid copolymer (e) from quarteramination-sulfonation (Route II) has some aggregated particles and form clusters regions in the hybrid matrix, which can also be attributed to the ionic interactions between those charged groups.