The bioavailability of acyclovir to the ophthalmic epithelium is low and when the drug is administered in ophthalmic ointment it must be applied every four hours. An emulsification technique has been used to prepare acyclovir-loaded chitosan microspheres with the aim of promoting the prolonged release of drug and increasing its ocular bioavailability. The microparticulate drug-delivery systems obtained have been characterized for their morphology and physicochemical characteristics by in-vitro dissolution tests and in-vivo ocular administration to rabbits. The results show that the microspheres obtained are always quite small--the diameters of 90% of the particles are < or = 25 microns (i.e. d 90% never exceeds 25 microns) and physicochemical characterization shows that the drug is homogeneously dispersed in an amorphous state inside the microspheres. The in-vitro dissolution profile of acyclovir from chitosan microspheres is slower than that for the raw drug. Results from in-vivo ocular administration of acyclovir-loaded microspheres to the rabbit eye show prolonged high concentrations of acyclovir and increased AUC values. The microparticulate drug-carrier seems a promising means of topical administration of acyclovir to the eye.

A novel anticancer vaccine candidate built on a nonpeptidic scaffold has been synthesized. Four S-Tn tumor-associated glycomimetic antigens have been clustered onto a calix[4]arene scaffold bearing an immunoadjuvant moiety (P3CS). The immunogenicity of the synthetic construct has been investigated by immunization of mice in vivo. ELISA assay has evidenced that the tetravalent construct stimulates a higher production of anti-Tn antigen IgG antibodies when compared to an analogous monovalent compound. This result is ascribable to an antigen cluster effect and makes the reported vaccine candidate a good mimic of the natural motifs present on the mucine surface.

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MUC1 protein overexpressed in human epithelial carcinoma is a target in development of novel anticancer vaccines. Multiple units of immunodominant B-cell epitope PDTRP MUC1 core sequence were conjugated to calix[4,8]arene platforms containing TLR2 ligand, to produce two novel anticancer self-adjuvant vaccine candidates. The immunogenicity of the synthetic constructs was investigated by immunization of mice in vivo. ELISA assay evidenced that the vaccine candidates stimulate anti MUC1 IgG antibody production (major for the octavalent construct) and no additive effect but a multivalency effect was observed when compared to an analogous monovalent. Octa- and tetravalent constructs lacking in PDTRP peptide moieties did not show anti MUC1 IgG antibody production in mice. The antibodies induced by the synthesized constructs are able to recognize the MUC1 structures present on MCF7 tumor cells. The results display that calixarenes are convenient platforms for building multicomponent self-adjuvant vaccine constructs promising as immunotherapeutic anticancer agents.

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Synaptic ribbons of the outer plexiform layer in the retina of albino rats are examined, with particular regard to their ultrastructure and to their chronobiological behaviour. As to the ultrastructure, aside from the typical lamellar and granular morphology, synaptic ribbons, whose central bar is roundish and granular, delaminate or furnished with enlarged extremities, are shown. As to the chronobiological pattern, synaptic ribbons undergo to circadian changes in their absolute number, being particularly numerous during the light phase, and few during darkness. It is also considered the morphology (ratio between granular and lamellar) and the size (long, intermediate and short) during the 24-hour cycle; in both cases, diphasic curves are observed. On the basis of these results, in the junction photoreceptors-bipolar cells, synaptic ribbons are polymorphic, dynamic structures, whose number and morphology strictly depend on environmental light conditions.

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