RESUMO
The aim of this work was to assess the feasibility of drug nanosystems combination for oral therapy of multibacillary leprosy. The anti-leprotic drugs dapsone (DAP) and clofazimine (CLZ) were incorporated within polymeric nanosystems and studied per se and in combination. DAP was loaded in Eudragit L100 nanoparticles (NPs-DAP) while CLZ was loaded in (poly(lactic-co-glycolic acid) (NPs-CLZ). The nanosystems exhibited around 200â¯nm in size and a drug loading of 12% for each drug. In vitro cytotoxicity on intestinal Caco-2 cells revealed that after 8â¯h incubation, DAP alone and within NPs were not toxic up to 100⯵gâ¯mL-1, while CLZ per se was toxic, reducing cell viability to 30% at 50⯵gâ¯mL-1. Caco-2 exposed to the combination of NPs-DAP (100⯵gâ¯mL-1) and NPs-CLZ (50⯵gâ¯mL-1) exhibited 80% of viability. Caco-2 monolayer permeability assays revealed that DAP and CLZ in the nanosystems per se or in NPs-DAP/ NPs-CLZ combination crossed the intestinal barrier. No significant differences were observed between the single nanosystems or in combination with the apparent permeability values and the amount of permeated drug. Thus, the NPs-DAP/NPs-CLZ combination seems to be a promising platform to deliver both drugs in association, representing an important step towards the improvement of multibacillary leprosy therapy.
Assuntos
Clofazimina/farmacologia , Dapsona/farmacologia , Sistemas de Liberação de Medicamentos , Intestinos/fisiologia , Nanopartículas/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Impedância Elétrica , Humanos , Intestinos/efeitos dos fármacosRESUMO
AIM: To optimize the production of pH-sensitive dapsone (DAP) nanoparticles based on Eugradit L100 (NPs-EL100-DAP) for oral delivery. MATERIALS & METHODS: NPs-EL100-DAP were optimized using a Plackett-Burman design and a Box-Behnken design. The physicochemical properties of the obtained nanoparticles were monitored by microscopy, dynamic light scattering, Fourier transform infrared spectroscopy, differential scanning calorimetry, in vitro release assays, and examined for cytotoxicity and permeation across intestinal barrier. RESULTS: The in vitro release assay of NPs-EL100-DAP confirmed the nanoparticles' pH sensitivity and the ability to deliver DAP at intestinal environment. NPs-EL100-DAP demonstrated enhanced intestinal interactions in comparison to free DAP, across Caco-2 monolayers. CONCLUSION: These studies demonstrate the potential of NPs-EL100-DAP as a therapeutic platform for oral treatment of leprosy.