Preparation and Characterization of Chitosan Nanoparticles for Zidovudine Nasal Delivery.

Zidovudine (AZT) is the antiretroviral drug most frequently used for the treatment of Acquired Immunodeficiency Syndrome. Its low oral bioavailability demands the development of innovative strategies to overcome the first pass metabolism. The nasal route is an option for enhanced therapeutic efficacy and to reduce the extent of the first-pass effect. In this article, AZT loaded chitosan nanoparticles were prepared by a modified ionotropic gelation method with sodium tripolyphosphate. The increase proportion of CS (NP1 10:01 (w/w)) promoted the formation of smaller nanoparticles (260 nm), while raising the proportion of TPP (NP2 5:1 w/w) increased the nanoparticles size (330 nm). The incorporation of AZT increased the nanoparticles size for both AZT-loaded nanoparticles AZT-loaded NP1 (406 nm) and AZT-loaded NP2 (425 nm). The incorporation of AZT into NP1 did not change the electrophoretic mobility, however, in AZT-loaded NP2 there was a significant increase. The positive surface of the nanoparticles is very important for the mucoadhesive properties due interaction with the sialic groups of the mucin. Nuclear resonance magnetic data showed that the higher concentration of chitosan in the nanoparticles favored the interaction of few phosphate units (pyrophosphate) by ionic interaction Scanning electron microscopy, revealed that the nanoparticles are nearly spherical shape with porous surface. The entrapment efficiency of AZT, was 17.58% ± 1.48 and 11.02% ± 2.05 for NP1 and NP2, respectively. The measurement of the mucoadhesion force using mucin discs and nasal tissue obtained values of NP1 = 2.12 and NP2 = 4.62. In vitro permeation study showed that the nanoparticles promoted an increase in the flux of the drug through the nasal mucosa. In view of these results, chitosan nanoparticles were found to be a promising approach for the incorporation of hydrophilic drugs and these results suggest that the CS-containing nanoparticles have great potential for nasal AZT administration.

In vitro evaluation of permeation, toxicity and effect of praziquantel-loaded solid lipid nanoparticles against Schistosoma mansoni as a strategy to improve efficacy of the schistosomiasis treatment.

Solid lipid nanoparticles (SLN) are a promising drug delivery system for oral administration of poorly-water soluble drugs because of their capacity to increase the solubility of drug molecules when loaded in their lipid matrices, with the resulting improvement of the drug bioavailability. In the present work, we have developed praziquantel (PZQ)-loaded SLN and explored the biological applications of this system for intestinal permeation of PZQ. The effect in vitro on Schistosoma mansoni culture and the cytotoxicity in HepG2 line cell were also evaluated. The results showed a significant decrease in the intestinal absorption of PZQ loaded in SLN compared to free PZQ, suggesting that the SLN matrix could act as reservoir system. In culture of S. mansoni, we observed that PZQ-loaded SLN were more effective than free PZQ, leading the death of the parasites in less time. The result was proportional to doses of PZQ (25 and 50 µg mL⁻¹) and lipid concentration. Regarding cytotoxicity, the encapsulation of PZQ into SLN decreased the toxicity in HepG2 cells in comparison to the free PZQ. From the obtained results, PZQ-loaded SLN could be a new drug delivery system for the schistosomiasis treatment especially in marginalized communities, improving the therapeutic efficacy and reducing the toxic effects of PZQ.