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Abstract: In this study, the spray drying technique was used to prepare ciprofloxacin microparticles (CFX-MPs) for pulmonary administration. By virtue of its amphoteric properties, CFX was dissolved in either a slightly alkaline or acidic solution depending on the used polymer. Dextran and chitosan were used to prepare the MPs and modify the release characteristics of the drug. Particle surface modification was done with either DPPC or PEG. The effects of the manufacturing and formulation parameters on the drug–polymer interactions were investigated by thermal analysis and infrared spectroscopy. CFX-MPs showed improved aerosolisation properties and the encapsulated drug possessed high antimicrobial activity against two of the common and resistant respiratory pathogens: Pseudomonas aeruginosa and Staphylococus aureus. MPs were safe on the lung epithelial cells. Modulation of particle characteristics and drug release was possible by altering not only the polymer but also the type of the acid from which the powders were spray dried. MPs prepared with glutamic and aspartic acids showed better characteristics than those prepared with acetic and hydrochloric acids. Dextran modified particles showed improved aerosolisation properties and safety on lung epithelial cells. [Copyright &y& Elsevier]

Abstract: In the present work, DNaseI loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for pulmonary delivery were prepared using emulsion solvent evaporation. The effects of the various formulation and experimental variables on the size and morphological characteristics of the particles as well as on the encapsulation efficiency were investigated. The stability of the encapsulated DNaseI was evaluated and the respirable fraction was determined. Cytotoxicity of the NPs was evaluated on lung epithelial cells. The results showed that by using leucine and dipalmito-phosphatidyl-choline (DPPC), discrete NPs with 76% retained biological activity were prepared. A high respirable fraction (particles below 6μm) reaching 71.3% was achieved after nebulization of the NP suspension. The results revealed the suitability of the prepared particles for pulmonary delivery and highlighted the role of excipients in the stabilization of DNaseI against the stresses encountered during preparation. [Copyright &y& Elsevier]

Abstract: Strangles is an infectious disease caused by Streptococcus equi subspecies equi that affects the upper respiratory tract of the Equidae. The control of this disease seems to be dependent on its earlier detection and prevention, but prolonged animal protection without development of strong and severe side effects has not yet been achieved. Convalescent horses exhibit a protective immune response, mainly against SeM (58kDa), an antiphagocytic and opsonogenic S. equi M-like protein, known as the major protective antigen against strangles. Purified recombinant SeM and S. equi protein extract-entrapped poly(lactic acid) (PLA) nanospheres were developed and their adjuvant potential was studied via the intramuscular route. The effect including molecules with adjuvant properties such as spermine, oleic acid, alginate and glycol-chitosan was also evaluated. Spherical nanometric particles <500nm containing the protein antigen were prepared by the solvent evaporation method and protein structure was not affected throughout preparation. The humoral immune response induced by nanospheres was markedly higher than that elicited by soluble antigens, isolated or co-admixed with CpG. The IgG and IgG subtypes, along with cytokine titres, indicated that nanospheres composed by glycolchitosan developed a more balanced Th1/Th2 response for both purified SeM and S. equi enzymatic extract proteins, although those induced by the pure antigen-entrapped particles were higher than the S. equi tested vaccines composed by total antigens entrapped in polymeric nanospheres. [Copyright &y& Elsevier]

Abstract: The nasal mucosa has many advantages as a potential site for drug and vaccine delivery. The present study has sought to exploit this route of delivery using microparticles composed of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a matrix material blended with poly(caprolactone) for nasal immunisation with diphtheria toxoid. Particles were prepared by a double emulsion method, followed by spray drying and the effect of TPGS on size, zeta potential, loading and release of antigen was assessed. Particles composed of TPGS–PCL blends were spherical, smooth and monodisperse, displaying increasing yields after spray drying with increasing concentrations of TPGS. The immune response to diphtheria toxoid loaded PCL-TPGS microspheres after nasal administration was shown to be higher than that achieved using PCL microspheres alone. We conclude that TPGS shows significant potential as a novel adjuvant either alone or in combination with an appropriate delivery system. [Copyright &y& Elsevier]