Depot subcutaneous injection with chalcone CH8-loaded Poly (Lactic-Co-Glycilic Acid) microspheres as a single-dose treatment of cutaneous leishmaniasis

Ariane de Jesus Sousa-Batista 1 Wallace Pacienza-Lima 1 Natalia Arruda-Costa 1 Camila Alves Bandeira Falcao 1 Maria Inês Ré 2 Bartira Rossi-Bergmann 1
1 IBCCF - Instituto de Biofísica Carlos Chagas Filho [Rio de Janeiro]
2 RAPSODEE - Centre de recherche d'Albi en génie des procédés des solides divisés, de l'énergie et de l'environnement
Abstract : Conventional chemotherapy of cutaneous leishmaniasis (CL) is based on multiple parenteral or intralesional injections with systemically toxic drugs. Aiming at a single-dose localized therapy, biodegradable PLGA (poly-(lactide-co-glycolide) microparticles loaded with 7.8% of an antileishmanial nitrochalcone named CH8 (CH8/PLGA) were constructed to promote sustained subcutaneous release. In vitro, murine macrophages avidly phagocytosed CH8/PLGA smaller than 6μm without triggering oxidative mechanisms. Upon 48-hour incubation, both CH8 and CH8/PLGA were 40 times more toxic to intracellular Leishmania amazonensis than to macrophages. In vivo, BALB/c were given one or three subcutaneous injections in the infected ear with 1.2mg/kg of CH8 in free or CH8/PLGA forms, while controls received three CH8-equivalent doses of naked PLGA microparticles or Glucantime. While a single injection with CH8/PLGA reduced the parasite loads by 91%, triple injections with free CH8 or CH8/PLGA caused 80% and 97% reduction, respectively, in relation to saline controls. Glucantime treatment was the least effective (only 36% reduction) and the most toxic as seen by elevated alanine aminotransferase serum levels. Together, those findings show that CH8/PLGA microparticles can be effectively and safely used for single-dose treatment of CL.
Keywords : cutaneous leishmaniasis microparticles chemotherapy depot PLGA polymeric microparticle
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Ariane de Jesus Sousa-Batista, Wallace Pacienza-Lima, Natalia Arruda-Costa, Camila Alves Bandeira Falcao, Maria Inês Ré, et al.. Depot subcutaneous injection with chalcone CH8-loaded Poly (Lactic-Co-Glycilic Acid) microspheres as a single-dose treatment of cutaneous leishmaniasis. Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2018, 62 (3), pp.art. e01822-17. ⟨10.1128/AAC.01822-17⟩. ⟨hal-01712186⟩

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