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Poor bioavailability of drugs associated with their poor solubility limits the clinical effectiveness of almost 40% of the newly discovered drug moieties. Low solubility, coupled with a high log p value, high melting point and high dose necessitates exploration of alternative formulation strategies for such drugs. One such novel approach is formulation of the drugs as “Nanocrystals”. Nanocrystals are primarily comprised of drug and surfactants/stabilizers and are manufactured by “top-down” or “bottom-up” methods. Nanocrystals aid the clinical efficacy of drugs by various means such as enhancement of bioavailability, lowering of dose requirement, and facilitating sustained release of the drug. This effect is dependent on the various characteristics of nanocrystals (particle size, saturation solubility, dissolution velocity), which have an impact on the improved performance of the nanocrystals. Various sophisticated techniques have been developed to evaluate these characteristics. This article describes in detail the various characterization techniques along with a brief review of the significance of the various parameters on the performance of nanocrystals.

Vaccines delivered via the mucosal route have logistic benefits over parenteral or intramuscular vaccines as they offer patient compliance. This study presents the first intranasal, controlled release, subunit nanovaccine comprising mucoadhesive tamarind seed polymer (xyloglucan) based nanoparticles produced using an efficient, environmentally compatible, and industrially scalable technique: rapid expansion of supercritical solution. The nanovaccine formulation aimed against brucellosis comprised xyloglucan nanoparticles loaded separately with antigenic acellular lipopolysaccharides from B. abortus (S19) and the immunoadjuvant quillaja saponin. The nanovaccine elicited prolonged humoral and cell-mediated immunity in female Balb/c mice. Nasal vaccination with the nanovaccine resulted in higher levels of mucosal IgA and IgG than with an aqueous solution of soluble lipopolysaccharides and quillaja saponin. Systemic immunity triggered by the nanovaccine was evidenced by higher IgG levels in sera post priming and boosting. The nanovaccine induced a mixed Th1/Th2 type of immunity with higher IgG2a levels and thus a polarized Th1 response. The results suggest that the nanovaccine administered by homologous nasal route can prime the immune system via the mucosal and systemic pathways and is a good candidate for vaccine delivery.

Brucellosis is a zoonotic disease that causes significant negative impacts on the animal industry and affects over half a million people worldwide every year. The limited safety and efficacy of current animal brucellosis vaccines, combined with the lack of a licensed human brucellosis vaccine, have led researchers to search for new vaccine strategies to combat the disease. To this end, the present research aimed to evaluate the safety and efficacy of a green vaccine candidate that combines Brucella abortus S19 smooth lipopolysaccharide (sLPS) with Quillaja saponin (QS) or QS-Xyloglucan mix (QS-X) against mucosal brucellosis in BALB/C mice. The results of the study indicate that administering two doses of either sLPS-QS or sLPS-QS-X was safe for the animals, triggered a robust immune response, and enhanced protection following intranasal challenge with S19. Specifically, the vaccine combinations led to the secretion of IgA and IgG1 in the BALF of the immunized mice. We also found a mixed IgG1/IgG2a systemic response indicating evidence of both Th1 and Th2 activation, with a predominance of the IgG1 over the IgG2a. These candidates resulted in significant reductions in the bioburden of lung, liver, and spleen tissue compared to the PBS control group. The sLPS-QS vaccination had conferred the greatest protection, with a 130-fold reduction in Brucella burdens in lung and a 55.74-fold reduction in the spleen compared to PBS controls. Vaccination with sLPS-QS-X resulted in the highest reduction in splenic Brucella loads, with a 364.6-fold decrease in bacterial titer compared to non-vaccinated animals. The study suggests that the tested vaccine candidates are safe and effective in increasing the animals’ ability to respond to brucellosis via mucosal challenge. It also supports the use of the S19 challenge strain as a safe and cost-effective method for testing Brucella vaccine candidates under BSL-2 containment conditions.

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