Mucoadhesive improvement of alginate microspheres as potential gastroretentive delivery carrier by blending with Bletilla striata polysaccharide.

As polysaccharide from Bletilla striata (BSP) was anticipated with mucoadhesive improvement in sodium alginate (SA) microspheres, BSP was mixed with SA to construct a composite microsphere to retain in the gastrointestinal tract for a long time. The morphological properties, particle size and thermodynamic properties of the microspheres in combination with comprehensive evaluations in the swelling properties, mucin adsorption, ex vivo and in vivo gastric retention were determined to characterize the mucoadhesion of SA-BSP blend microspheres. Results showed that the prepared microspheres were discrete and spherical. The addition of BSP increased flexibility and reduced rigidity of SA microsphere. Furthermore, the swelling property, mucin adsorption ability and the retention rate on the gastric mucosa of SA matrix were increased after blending with BSP. Mucoadhesion tests showed the SA-BSP microspheres stayed much longer in rats' stomach than the SA microsphere did. Above all, the SA-BSP microspheres with the enhanced mucoadhesion suggested being a potential drug carrier in developing the gastroretentive drug delivery system.

The formulation and immunisation of oral poly(DL-lactide-co-glycolide) microcapsules containing a plasmid vaccine against lymphocystis disease virus in Japanese flounder (Paralichthys olivaceus).

Nucleic acid-based immunotherapy is a new treatment option for fish immunisation in intensive culture. However, DNA-based vaccines would be hydrolyzed or denaturized because of the existence of nucleases and severe gastrointestinal conditions. Poly(DL-lactide-co-glycolide) (PLGA) microcapsules, loaded with plasmid DNA (pDNA) against lymphocystis disease virus (LCDV), were prepared by modified water in oil in water (W/O/W) double emulsion method in our laboratory. Encapsulation efficiency, loading percent and diameter of microcapsules were 78-88%, 0.5-0.7% and less than 10 mum, respectively. In simulated gastric fluid (SGF), less than 10% of pDNA was released from microcapsules in 12 h, and about 6.5% of pDNA was released in 12 h in simulated intestinal fluid (SIF). The content of the supercoiled of pDNA in microcapsules and control was 80% and 89% respectively, which indicated that a little supercoiled pDNA degradation occurred during encapsulation. RT-PCR showed that lots of RNA containing information of MCP gene existed in all tissues of fish vaccinated with microcapsules 10-90 days after oral administration. SDS-PAGE and immunoblots, as well as immunofluorescence images, displayed that major capsid protein (MCP) of LCDV was expressed in tissues of fish vaccinated with pDNA-loaded microcapsules. In addition, indirect enzyme-linked immunosorbent assay (ELISA) showed that the immune responses of sera were positive (O.D> or =0.3) from week 1 to week 24 for fish vaccinated with microcapsules, in comparison with fish vaccinated with naked pDNA. Our results suggested that PLGA microcapsules were promising oral carriers for pDNA delivery. This encapsulation technique had potential for drug delivery applications due to its ease of operation and notable immunisation efficacy.

Rheological and mucoadhesive properties of polysaccharide from Bletilla striata with potential use in pharmaceutics as bio-adhesive excipient.

This study described the rheological and mucoadhesive properties of one natural water-soluble polysaccharide from Bletilla striata (BSP). The rheological characteristics of BSP in aqueous solutions and BSP mixed with other polymers were investigated under various conditions, including concentration, temperature, pH, and salt addition. Viscometric studies and ex vivo mucoadhesion tests were also conducted to examine the mucoadhesive properties of BSP. Results indicated that BSP behaved as a shear-thinning fluid at various concentrations, and its viscosity decreased at high temperatures. The viscous flow properties of the BSP mixtures changed at high pH (>5.0). Conversely, the viscosity of the BSP solutions was slightly affected by electrolytes. The viscosities of the BSP mixtures with four other commonly used polymers (sodium alginate, sodium carboxymethyl cellulose, hypromellose, and chitosan) were enhanced. The synergistic viscosity of BSP/mucin mixtures increased as BSP concentrations increased, and the maximum value was observed in the SIF medium without enzymes. The adhesive abilities of 5.0% and 10.0% BSP were almost equivalent to that of 0.5% sodium alginate, suggesting that BSP exhibited a certain mucoadhesive property, although it was weaker than that of the other commonly used mucoadhesive materials. BSP showed potential for pharmaceutical excipient applications in bioadhesive drug delivery systems.

High dispersed phyto-phospholipid complex/TPGS 1000 with mesoporous silica to enhance oral bioavailability of tanshinol.

Phenolic acids are widely distributed in the plant kingdom and possess a broad spectrum of pharmacological activity. However, low oral bioavailability restricts their application. In this study, a high dispersed phyto- phospholipid complex with mesoporous silica containing TPGS 1000 (TPC-SD) was fabricated using Tanshinol (Tan) as model drug. Phospholipid complex (PC) was employed to improve the n-octanol/water partition coefficient (log P) and apparent permeability coefficients (Papp) of Tan. Mesoporous silica was used to compensate for the negative effects of phospholipid on drug's dispersion and dissolution owing to its viscosity and poor water-solubility. TPGS 1000, a P-gp inhibitor, was used to block the efflux of Tan. Log P tests showed that the lipophilicity of Tan was significantly enhanced by Tanshinol phospholipid complex (TPC) formation. In vitro dissolution results showed that the cumulative dissolution percentage of Tan from TPC-SD was 4.33- fold of that from TPC in 120 min A Caco-2 permeability test confirmed that Papp (AP-BL) of TPC and TPC-SD increased approximately 2.22- and 3.53- fold compared to those of unformulated Tan, respectively (p < 0.01, p < 0.01). Pharmacokinetic studies demonstrated that the AUC0-∞ of TPC-SD was 2.23- and 1.47- fold compared with those of unformulated Tan and TPC, respectively (p < 0.01, p < 0.01). These results indicated that the high dispersed phyto- phospholipid complex/TPGS 1000 by mesoporous silica can be a promising drug delivery system to improve the oral bioavailability of free phenolic acids.

Study on poly(vinyl alcohol)/carboxymethyl-chitosan blend film as local drug delivery system.

The distinguishable films composed of poly(vinyl alcohol) (PVA) and carboxymethyl-chitosan (CMCS) were prepared by blending/casting method, and loaded with ornidazole (OD) as local drug delivery system. In vitro test, the blend films showed pH-responsive swelling behavior and moderate drug release action, and also exhibited a little antimicrobial activity against E. coli and S. aureus strains. Those characteristics of CMCS/PVA blend films were essentially governed by the weight ratio of CMCS and PVA. Increasing the content of PVA in blend film would decrease swelling and decelerated the drug release. However, increasing the content of CMCS would enhance the antimicrobial activity. The biocompatibility and bioactivity of the blend film were also evaluated using rabbit blood and Wister rats. This blend drug system was of no hemolysis, no toxicity to rat periodontia and no cytotoxicity to the rat muscle. After subcutaneously implanting the blend drug films in Wister rat, the systems kept a good retention at the application site and maintained high drug concentration in long time (5 days) which was longer than the period of drug released in vitro (160 min).