Mei Dai

A novel injectable local hydrophobic drug delivery system: Biodegradable nanoparticles in thermo-sensitive hydrogel.

In this article, a novel local hydrophobic drug delivery system: nanoparticles in thermo-sensitive hydrogel, was demonstrated. First, honokiol, as a model hydrophobic drug, loaded poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) nanoparticles were prepared by emulsion solvent evaporation method, and then were incorporated into thermo-sensitive F127 hydrous matrix. The obtained injectable hydrophobic drug delivery system can act as a depot for sustained release of honokiol in situ. The lower critical solution temperature (LCST) of the composite matrix increases with increase in the mass of incorporated nanoparticles, or with decrease in the amount of residual organic solvent in the system. Honokiol release profile in vitro was studied, and the results showed that honokiol could be sustained released from the system. The described injectable drug delivery system might have great potential application for local delivery of hydrophobic drugs such as honokiol.

Chitosan-alginate sponge: preparation and application in curcumin delivery for dermal wound healing in rat.

A biodegradable sponge, composed of chitosan (CS) and sodium alginate (SA), was successfully obtained in this work. The sponge was ethereal and pliable. The chemical structure and morphology of the sponges was characterized by FTIR and SEM. The swelling ability, in vitro drug release and degradation behaviors, and an in vivo animal test were employed to confirm the applicability of this sponge as a wound dressing material. As the chitosan content in the sponge decreased, the swelling ability decreased. All types of the sponges exhibited biodegradable properties. The release of curcumin from the sponges could be controlled by the crosslinking degree. Curcumin could be released from the sponges in an extended period for up to 20 days. An in vivo animal test using SD rat showed that sponge had better effect than cotton gauze, and adding curcumin into the sponge enhanced the therapeutic healing effect.

A thermosensitive hydrogel based on biodegradable amphiphilic poly(ethylene glycol)–polycaprolactone–poly(ethylene glycol) block copolymers

A series of low molecular weight poly(ethylene glycol)–polycaprolactone–poly(ethylene glycol) (PEG–PCL–PEG) biodegradable block copolymers were successfully synthesized using isophorone diisocyanate (IPDI) as the coupling agent, and were characterized using 1H NMR and Fourier transform infrared spectroscopy. The aqueous solutions of the PEG–PCL–PEG copolymers displayed a special thermosensitive gel–sol transition when the concentration was above the corresponding critical gel concentration. Gel–sol phase diagrams were recorded using the test-tube-inversion method; they depended on the hydrophilic/hydrophobic balance in the macromolecular structure, as well as some other factors, including the heating history, volume, and the ageing time of the copolymer aqueous solutions and dissolution temperature of the copolymers. As a result, the gel–sol transition temperature range could be altered, which might be very useful for application in injectable drug delivery systems.

Preparation of mannan modified anionic PCL–PEG–PCL nanoparticles at one-step for bFGF antigen delivery to improve humoral immunity ☆

In this article, blank anionic poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) and anionic mannan modified PCEC (MPCEC) nanoparticles with nearly the same particle size and zeta potential were prepared by emulsion solvent evaporation method. Human basic fibroblast growth factor (bFGF) was absorbed onto anionic nanoparticles surface due to electrostatic interaction. The obtained bFGF-nanoparticles complexes were injected subcutaneously into C57BL/6 mice at 20 microg of bFGF/dose on week 0, 1, 2 and 3. The mice serum was collected on week 4, and bFGF-specific autoantibody total IgG, IgG1 and IgG2a titer in serum was determined by ELISA. The results indicated that the autoantibody IgG, IgG1 and IgG2a titer of the mice immunized by bFGF-MPCEC complexes were higher than that immunized by either bFGF-PCEC or bFGF-Alum. This phenomenon might be due to that mannan functionalized MPCEC nanoparticles could be targeted to dendritic cells (DCs) to improve humoral immunity. The prepared anionic mannan modified PCEC nanoparticles (MPCEC) might have great potential application in vaccine delivery systems.

Preparation of camptothecin-loaded PCEC microspheres for the treatment of colorectal peritoneal carcinomatosis and tumor growth in mice

The aim of this study was to prepare PCL-PEG-PCL (PCEC) microspheres to protect camptothecin from hydrolysis, to extend its release time and to enhance its treatment efficacy on colorectal peritoneal carcinomatosis and tumor growth in mice. Camptothecin (CPT)-loaded PCL-PEG-PCL (PCEC) microspheres were prepared by oil-in-water emulsion solvent evaporation method. The particle size, morphological characteristics, encapsulation efficiency, in vitro drug release studies and in vitro cytotoxicity of CPT-loaded PCEC microspheres have been investigated. In vivo studies were carried out on Balb/c male mice bearing colorectal peritoneal carcinomatosis. CPT-loaded PCEC microspheres were applied to abdominal cavity of mice once a week. Free CPT was used as a positive control. On 14th day of treatment, mice were sacrificed and antitumor activities of CPT-loaded PCEC microspheres were evaluated. Compared with control group, a significant decrease in the number of tumor nodes was observed in group treated with CPT-loaded PCEC microspheres. Immunohistochemistry staining of tumor tissues with CD34 revealed that MVD positive cells were significantly reduced in CPT-loaded PCEC microspheres treated group in contrast to other groups (P<0.05). The CPT-loaded PCEC microspheres were considered potentially useful to treat the abdominal metastases of colon carcinoma.

Preparation of anionic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) copolymeric nanoparticles as basic protein antigen carrier

It is an useful method for polymeric nanoparticles to load protein by electrostatic method to improve the immunogenicity of protein antigen. In this article, anionic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC) nanoparticles were prepared by modified emulsion solvent evaporation method, and human basic fibroblast growth factor (bFGF), as a model protein, was absorbed onto its surface due to electrostatic interaction. The prepared anionic PCEC nanoparticles, with mean diameter of 136.9 nm, had zeta potential of − 33.14 mV. The surface charge and particle size of bFGF/nanoparticles complex increased with increase of bFGF/nanoparticles mass ratio. The encapsulated bFGF could be released slowly from bFGF/nanoparticle complexes. The animal experiment indicated that the humoral immunity induced by bFGF/PCEC complex was improved greatly than that created by naked bFGF. Otherwise, the cytotoxicity of anionic PCEC nanoparticles was also evaluated by 293 cell viability. The prepared anionic PCEC nanoparticles might have great potential application as basic protein vaccine delivery system.

Preparation, characterization, and in vitro cytotoxicity study of cationic PCL-Pluronic-PCL (PCFC) nanoparticles for gene delivery

In this article, poly(epsilon-caprolactone)-pluronic-poly(epsilon-caprolactone) (PCFC) copolymer was synthesized by ring-opening polymerization and characterized by 1H-NMR and GPC. Cationic PCFC nanoparticles were prepared at one-step by modified emulsion solvent evaporation method using cetyltrimethylammonium bromide as the stabilizer. The cytotoxicity of PCFC nanoparticles was studied here with and without serum. The obtained cationic PCFC nanoparticles were employed to condense and adsorb DNA onto its surface. And it could protect plasmid GFP (pGFP) from enzymatic degradation and acidic degradation in a certain period. Release behavior of pGFP from the pGFP/PCFC nanoparticles complex was also studied in vitro. The obtained cationic PCEC nanoparticles might have great potential application in DNA delivery.

Improving therapeutic effect in ovarian peritoneal carcinomatosis with honokiol nanoparticles in a thermosensitive hydrogel composite

Ovarian cancer is one of the most common carcinomas and causes lots of deaths in the world. Honokiol (HK), a natural product, was proved to be a potent anti-tumor agent, however the hydrophobicity of HK limited its application. In this work, we investigated the anti-tumor efficacy of honokiol nanoparticles (HK-NPs) and honokiol nanoparticles-loaded thermosensitive hydrogel (HK-NPs/hydrogel) on ovarian cancer in vitro and in vivo. HK-NPs with small particle size and high drug loading were prepared, and HK-NPs/hydrogel with a sol–gel transition temperature at about body temperature was also obtained. In addition, HK-NPs and HK-NPs/hydrogel showed a sustained release behavior of HK in vitro. HK-NPs could effectively inhibit proliferation of SKOV3 tumor cells in a dose- and time-dependent manner and induce apoptosis of tumor cells in vitro. Furthermore, compared with controlled groups, HK-NPs and HK-NPs/hydrogel dramatically inhibited growth of tumors and prolonged the survival of mice bearing ovarian peritoneal carcinomatosis (OPC), and the effects of HK-NPs/hydrogel were more obvious than HK-NPs (P < 0.05). Intraperitoneal chemotherapy with HK-NPs/hydrogel significantly inhibited proliferation activity and angiogenesis of tumors and increased apoptosis and necrosis in tumor tissues. Therefore, our results suggested that HK-NPs/hydrogel may have great potential in clinical applications in the treatment of OPC.