A water-insoluble anticancer agent, camptothecin (CPT) was incorporated to a polymeric micelle carrier system preparing from cholic acid chitosan-grafted poly (ethylene glycol) methyl ether (CS-mPEG-CA). CS-mPEG-CA formed a core–shell micellar structure with a critical micelle concentration (CMC) of 7.08 μg/ml. Incorporation efficiency was investigated by varying physical incorporation method and initial drug loading. Among three incorporation methods (dialysis, emulsion and evaporation methods), an emulsion method showed the highest CPT incorporation efficiency. Increasing the initial CPT loading from 5 to 40%, the incorporation efficiency decreased. In all examined CPT-loaded CS-mPEG-CA micelles, 5% initial drug loading showed the highest drug incorporation efficiency. Release of CPT from the micelles was sustained when increasing the initial CPT loading. This indicates the importance of incorporation method and the initial drug loading to obtain the optimum particle size with high drug loading and sustained drug release. When compared to the unprotected CPT, CPT-loaded CS-mPEG-CA micelles were able to prevent the hydrolysis of the lactone group of the drug. This novel CS-mPEG-CA polymer presents considerable potential interest in the further development of CPT carrier. 相似文献
Stearic acid grafted chitosan oligosaccharide (CSO-SA) with different degree of amino substitution (SD) was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The critical micelle concentration (CMC) of CSO-SA with different SD was about 0.06, 0.04, 0.01 mg/ml, respectively. With the increase of micelle concentration, the micelle size decreased, and the zeta potential increased. On the other hand, with the increase of SD of CSO-SA, the micelle size and zeta potential decreased due to the increased hydrophobic interaction of SA and the reduced free amino groups. To increase the stability of the micelle in vivo and controll drug release, the shells of micelles were cross-linked by glutaraldehyde. By controlling the molar ratio of CSO-SA to glutaraldehyde, the cross-linking of intra-micelle could be reached, and the nanoparticle with smaller size than that of its initial micelle was obtained. Paclitaxel was then used as model drug to incorporate into the micelles, and the surfaces of the micelles were further cross-linked by glutaraldehyde to form drug loaded and shell cross-linked nanoparticles. The effects of drug loading, SD of CSO-SA and cross-link degree on the size, zeta potential, drug entrapment efficiency and in vitro drug release behavior of micelles and its cross-linked nanoparticles were investigated. The higher drug entrapment efficiencies (above 94%) were observed in all case. The charged amounts of drug did not affect the drug release behavior. The drug release rate decreased with the increase of SD of CSO-SA and cross-link degree. 相似文献
A series of poly(?‐caprolactone/glycolide)‐poly(ethylene glycol) (P(CL/GA)‐PEG) diblock copolymers were prepared by ring opening polymerization of a mixture of ?‐caprolactone and glycolide using mPEG as macro‐initiator and stannous octoate as catalyst. Self‐assembled micelles were prepared from the copolymers using nanoprecipitation method. The micelles were spherical in shape. The micelle size was larger for copolymers with longer PEG blocks. In contrast, the critical micelle concentration of copolymers increased with decreasing the overall hydrophobic block length. Drug loading and drug release studies were performed under in vitro conditions, using paclitaxel as a hydrophobic model drug. Higher drug loading was obtained for micelles with longer poly(ε‐caprolactone) blocks. Faster drug release was obtained for micelles of mPEG2000 initiated copolymers than those of mPEG5000 initiated ones. Higher GA content in the copolymers led to faster drug release. Moreover, drug release rate was enhanced in the presence of lipase from Pseudomonas sp., indicating that drug release is facilitated by copolymer degradation. The biocompatibility of copolymers was evaluated from hemolysis, dynamic clotting time, and plasma recalcification time tests, as well as MTT assay and agar diffusion test. Data showed that copolymer micelles present outstanding hemocompatibility and cytocompatibility, thus suggesting that P(CL/GA)‐PEG micelles are promising for prolonged release of hydrophobic drugs. 相似文献
A novel and well-defined pH-sensitive amphiphilic triblock copolymer brush poly(lactide)-b-poly(methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether monomethacrylate) (PLA-b-PMAA-b-PPEGMA) and its self-assembled micelles were developed for oral administration of hydrophobic drugs. The copolymer and its precursors were synthesized by the combination of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and ring-opening polymerization (ROP) techniques. The molecular structures and characteristics were confirmed by GPC, (1)H NMR, and FT-IR. The critical micelle concentration (CMC) values of PLA-b-PMAA-b-PPEGMA in aqueous medium varied from 1.4 to 2.6 mg/L, and the partition equilibrium constant (K(v)) of pyrene in micellar solutions ranged from 2.873 × 10(5) to 3.312 × 10(5). The average sizes of the self-assembled blank and drug-loaded micelles were 140-250 nm determined by DLS in aqueous solution. The morphology of the micelles was found to be spherical by SEM. Nifedipine (NFD), a poorly water-soluble drug, was selected as the model drug and wrapped into the core of micelles via dialysis method. The in vitro release behavior of NFD from the micelles was pH-dependent. In simulated gastric fluid (SGF, pH 1.2), the cumulative release percent of NFD was relative low, while in simulated intestinal fluid (SIF, pH 7.4), more than 96% was released within 24 h. All the results showed that the pH-sensitive PLA-b-PMAA-b-PPEGMA micelle may be a prospective candidate as oral drug delivery carrier for hydrophobic drugs with controlled release behavior. 相似文献
This paper presented an interesting nanoparticle-based drug-delivery system with morphology transition behavior depending on the content of exposed PEG chain on the particle surface and a likely mechanism for the morphological transition of the rod-coil graft copolymer mPEG-g-CS was proposed. 相似文献
The aim of this investigation was to develop 5-fluorouracil (5-FU) loaded chitosan nanoparticles (CH-DNPs) for ophthalmic delivery. CH-DNPs were fabricated by ionotropic gelation mechanism using chitosan (CH) and a polyanion (TPP). The nanoparticles were smooth and spherical, confirmed by scanning electron microscopy (SEM) and atomic force microscope (AFM). CH/TPP mass ratio and TPP significantly changed the particles size morphology and encapsulation efficiency. The nanoparticles size ranged from approximately 114 to 192 nm and had a positive zeta potential (30±4 mV). The encapsulation efficiency, loading capacity and recovery of DNPs were 8.12-34.32%, 3.14-15.24% and 24.22 to 67% respectively. Physical characterization was done by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD). No interaction was observed in between drug and polymer and crystallinity of drug was not changed in drug loaded nanoparticles. In-vitro release study of DNPs showed diffusion controlled release. Bioavailability study of batch CS9 was studied in rabbit eye and compare to 5-FU solution. 5-FU level was significantly higher in aqueous humor of rabbit eye. Ocular tolerance was studied in the eye of New Zealand rabbits and tested formulation was non-irritant with no sign of inflammation. 相似文献
Methoxy poly(ethylene glycol)-grafted-chitosan (mPEG-g-CS) conjugates were synthesized by formaldehyde linking method and characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1H-NMR). The degree of substitution (DS) of methoxy poly (ethylene glycol) (mPEG) in the mPEG-g-CS molecules determined by 1H-NMR ranged from 19% to 42%. The critical aggregation concentration (CAC) was determined by fluorescence spectroscopy using pyrene as fluorescence probe and its value was 0.07 mg/mL in water. mPEG-g-CS formed monodisperse self-aggregated nanoparticles with a roughly spherical shape and a mean diameter of 261.9 nm were prepared by the dialysis method. mPEG-g-CS self-aggregated nanoparticles were used as carriers of poorly water-soluble anticancer drug methotrexate (MTX). MTX was physically entrapped inside mPEG-g-CS self-aggregated nanoparticles by dialysis method and the characteristics of MTX-loaded mPEG-g-CS self-aggregated nanoparticles were analyzed using dynamic laser light scattering (DLLS), transmission electron microscopy (TEM). Moreover, in vitro release behavior of MTX was also investigated and the results showed that MTX was continuously released more than 50% in 48 h. 相似文献
We herein develop a facile catalyst‐free method to prepare hyperbranched hydroxyl‐enriched aliphatic polycarbonate according to SCROP strategy. PEG‐attached multiarm hyperbranched copolymer HEHDO‐star‐mPEG was further designed. It was found that HEHDO‐star‐mPEG can self‐assemble into supramolecular multimolecular micelles in water. HEHDO‐star‐mPEG micelle showed excellent stability with respect to micellar size upon dilution, and displayed good cell‐biocompatibility. An anticancer drug of doxorubicin with hydrogen‐bonding functionality was incorporated into obtained micelles to establish a drug delivery system model. A high drug‐loading content as well as sustained release pattern for HEHDO‐star‐mPEG based delivery system was achieved.
β-Elemene is a volatile oil used for the treatment of cancer,but poor solubility,low bioavailability,and various adverse reactions limit its application.For amelio rating risks of the venous toxicity ofβ-elemene,intravenously injectable micelle ofβ-elemene was prepared using the thin-film hydration method.The results pointed out the micelles were uniformly spherical with about 20.96±0.1966 nm in average diameter and exhibited high entrapment efficiency(99.02%±0.88%).As revealed by drug release studies in vitro,β-elemene micelles had sustained drug release.Compared with freeβ-elemene,the micelles increased the drug cellular uptake and enhanced the anti-tumor effect in vitro through retarding cell cycle and inducing apoptosis.Meanwhile,the elevated se rum stability o fβ-elemene micelles implied less drug leakage and reduced toxicity.The wound healing and tube formation assay in vitro demonstrated the anti-metastasis and anti-angiogenesis effects ofβ-elemene micelles.Moreover,the pharmacokinetics study showed the AUC and T1/2 ofβ-elemene in micelle group were 1.79 and 1.62 times of that in free fi-elemene group,suggesting the circulation time ofβ-elemene in the blood had been prolonged.In addition,β-elemene micelles showed a favorable antitumor response compared with theβ-elemene solution on C26 colon cance r-bearing mice model.Local irritation study investigated in rabbits indicated that theβ-elemene micelles strikingly mitigated the irritation to the injection sites compared with freeβ-elemene.These results proved that the micelle could be a good candidate as an auspicious drug delivery system ofβ-elemene for the prospective clinical treatment of carcinoma. 相似文献
Herein we describe a new strategy for producing micelles with mixed coronal chains. This method involves attachment of an atom transfer radical polymerization (ATRP) initiator at the interface of a micelle and preparation of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes at the interface by a "grafting from" method. Poly(ethylene glycol)- block-polystyrene (PEG- b-PS) diblock copolymer was achieved by ATRP. After the sulfonation reaction PS blocks were partly sulfonated. In aqueous solution at low pH the sulfonated block copolymer self-assembled into micelles with PS cores and PEG coronae and sodium 4-styrenesulfonate groups were distributed at the interfaces of the micelles. An ATRP initiator consisting of a quaternary ammonium salt moiety and a 2-bromo-2-methyl propionate moiety was ion exchanged onto the interface of the micelle. ATRP of DMAEMA was initiated at the interface, and micelles with PEG/PDMAEMA mixed coronal chains were prepared by ATRP. The structures of the micelles were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and zeta potential measurements. The size and morphology of the micelles were controlled by pH in aqueous solution. At high pH, PDMAEMA brushes collapse, forming nanodomains on the surface of the micelles. PDMAEMA brushes in the coronae of the micelles could be used as a template for preparation of gold nanoparticles. 相似文献