Oral vaccination has long been regarded as the best alternative to conventional parenteral vaccination considering practical, economical, and immunological aspects. The purpose of this study was to develop albumin-chitosan mixed matrix microsphere-filled coated capsule formulations of Typhoid Vi antigen and to determine whether it can induce antigen-specific mucosal and systemic immune responses on oral administration. Formulations with Typhoid Vi antigen were prepared and filled into hard gelatin capsules (size # 9) and enteric coated. Formulations were characterized and administered to Sprague-Dawley rats to evaluate the induction of immune response to the antigen. The results indicated that the particle size, zeta potential, swelling, and disintegration rates were optimal for the oral delivery of microencapsulated vaccines. In vivo studies displayed multifold increase of antigen-specific IgG and IgA levels 8 weeks after oral immunization. No statistically significant difference in the antigen-specific IgG and IgA levels were found between oral and parenteral injection groups 8 weeks after vaccination. On the basis of the results of the study, it can be concluded that the oral administration of Typhoid Vi antigen microspheres was successful in inducing antigen-specific systemic and mucosal immune response.
As multidrug resistance continues to be a problem in cancer treatment, controlled release delivery systems, such as microspheres, may aid to give a slower release of anticancer drugs into drug resistant tumor cells. In this study doxorubicin microspheres microencapsulated in an albumin matrix were prepared via the spray-drying method and characterized for particle size, content analysis, and release studies. They were then evaluated in vitro using drug resistant murine melanoma tumor cells for uptake and efflux studies. Spray-drying produced a dispersed powder with a mean particle size of 4.91 ± 1.2 µm, 60% product yield, and encapsulation efficiency of 85% and a ζ potential range of 37 to -40 mV. Intracellular doxorubicin concentrations were higher in drug resistant tumor cells treated with microspheres as opposed to solution, and efflux of doxorubicin from the tumor cell was inhibited. Greater cytotoxic effects were seen in tumor cells treated with doxorubicin microspheres versus solution up to and after 3 days. In vivo pharmacokinetic studies conducted in male Sprague-Dawley rats, revealed a plasma-level time curve indicative of a two-compartment model, and showed prolonged half-life of doxorubicin, greater area under the plasma concentration time curve, and increased plasma concentrations of doxorubicin in rats at 8 and 24 h after administration of doxorubicin microspheres.
The aim of this study was to formulate and characterize microspheres containing antisense oligonucleotide to NF-kappaB using bovine serum albumin as the polymer matrix. Microspheres were prepared by spray-drying technique with 5, 10 and 15% drug loading. Glutaraldehyde was used as a cross-linking agent. The particle sizes ranged from 3-5 microm. Microspheres were smooth and spherical in shape, as determined by scanning electron microscopy (SEM). The yield of microspheres ranged from 70-75% and the encapsulation efficiencies were found to be in the range of 59-60%, as determined by a novel HPLC method. Zeta potential of the microspheres ranged between -39 to -53 mV, thus indicating good suspension stability in water. In-vitro release studies performed using phosphate buffer saline demonstrated extended drug release up to 72 h. Kinetic model fitting showed high correlation with the Higuchi model, suggesting that the drug release was primarily diffusion controlled.
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