Sublingual immunisation with GBS serotype III capsular polysaccharide-tetanus toxoid conjugate vaccine induces systemic and mucosal antibody responses which are opsonophagocytic and inhibit GBS colonisation of vaginal epithelial cells

No vaccines are currently licensed against Group B streptococcus (GBS), an important cause of morbidity and mortality in babies and adults. Using a mouse model, and in vitro opsonophagocytosis and colonisation assays, we evaluated the potential of a sublingually-administered polysaccharide-conjugate vaccine against GBS serotype III. Sublingual immunisation of mice with 10 µg of GBS conjugate vaccine once a week for 5 weeks induced a substantial systemic IgG anti-polysaccharide response which was similar to the level induced by subcutaneous immunsation. In addition, sublingual immunisation also induced mucosal (IgA) antibody responses in the mouth, intestines and vagina. Immune sera and intestinal washes were functionally active at mediating killing of the homologous GBS serotype III in an opsonophagocytosis assay. In addition, intestinal and vaginal washes inhibited the colonisation of mouse vaginal epithelial cells by the vaccine homologous strain. These results suggest that, in addition to the induction of high levels of IgG antibodies that could be transduced from the immunised mother to the foetus to protect the newborn against GBS infection, sublingual immunisation can elicit a substantial mucosal antibody response which might play an important role in the prevention of GBS colonisation in immunised women, thereby eliminating the risk of GBS transmission from the mother to the baby during pregnancy or at birth

PBPK modelling of ceftriaxone Na-loaded starch-sodium alginate polymeric blend prepared by water-in-oil emulsification for oral delivery

Ceftriaxone is a third-generation cephalosporin antibiotic effective against many bacterial infections. However, owing to its instability in the gastrointestinal tract (GIT), it is administered by injections, which is an unfavourable route of administration. Therefore, the aim of this study was to formulate ceftriaxone into biodegradable and thermally stable polymeric blend microparticles that are suitable for oral delivery. The drug-loaded microparticles were prepared by the water-in-oil (W/O) emulsion method and consisted of starch and sodium alginate (NaAlg) as a polymeric matrix and glutaraldehyde (GA) as a cross-linking agent. Characterization of these particles using scanning electron microscopy (SEM) showed that the particles were spherical in shape with a smooth surface. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) of these particles showed no drug-polymer interactions. The highest percentage yield of particles was obtained at 3% polymer concentration. The particle size increased slightly after drug loading. The drug loading and entrapment efficiency appeared to increase with increasing polymer concentration. In vitro drug release at pH 1.2 and pH 7.4, revealed that drug release was below 20% at the acidic pH, while at pH 7.4, drug release of up to 85% was observed. The release mechanism followed first-order and Fickian diffusion patterns. Plasma concentration-time profiles were simulated for subcontinental Asian populations using commercial PBPK software, and the results suggest that microencapsulation of ceftriaxone sodium in a polymeric blend could represent a promising approach for controlled oral delivery of the drug, with enhanced absorption and bioavailability of the drug