Therapeutic response and safety of the topical, sequential use of antiseptic, keratolytic, and pentamidine creams (3-PACK) on Leishmania (Viannia) braziliensis-infected mice

Abstract

BACKGROUND Topical treatment of New World cutaneous leishmaniasis can be affected by bacterial coinfection, hyperkeratosis, and transdermal drug delivery. OBJECTIVE The aim of this work was to evaluate the therapeutic response and safety of the topical, sequential use of antiseptic, keratolytic, and pentamidine isethionate (PMD) creams (3-PACK kit) on CL-infected BALB/c mice. METHODS A 0.5% chlorhexidine solution (CGH), 10% salicylic acid (SA), and 3% or 6% PMD were used as antiseptic, keratolytic, and antileishmanial drugs, respectively. During the first seven days, antiseptic, followed by 10% SA gel and PMD cream, were applied topically. Subsequently, treatment was performed only with the antiseptic and PMD creams. Skin irritation, reduction of lesion size (mm 2 ), and parasitic load were observed until 30 days of treatment were completed. FINDINGS The 3-PACK treatment using 6% PMD induced a complete lesion reduction in 3/6 mice and a partial reduction in 1/6 mice, with no parasites observed. In contrast, CGH and SA alone, along with the vehicle, were not effective (p < 0.05). Moderate to severe erythema was observed at the application site. MAIN CONCLUSION The topical 3-PACK using 6% PMD was 67% effective in the treatment of CL by Leishmania (Viannia) braziliensis . Currently, work is ongoing to improve PMD isethionate formulation and to determine a dose-response.

Discriminator for Cutaneous Leishmaniasis Using MALDI-MSI in a Murine Model

“…Muñoz et al created a collection of 25 MALDI-MSI spectral images obtained from a murine model, which were processed a method developed in association with Dr. Eduardo Chicano-Gálvez from the Instituto Mamoimonides de investigación biomédica (Cordoba, Spain). The tissue samples were obtained from biopsies of BALB/c mouse lesions with CL included in FFPE paraffin using two types of matrix α-cyano-4-hydroxycinnamic acid (HCCA) and 2,5-dihydroxybenzoic acid (DHB) . Mass spectrometry acquisition was performed on an AB SCIEX TOF/TOF 5800 (AB SCIEX, Framingham, USA) operating in positive reflector mode.…”

“…CL lesions include several layers of the skin and are characterized by presenting an asymptomatic or pruritic papule, which extends to form a nodular lesion with seropurulent exudate that, when drying, forms an attached crust or hyperkeratotic lesions . Analysis of CL lesion samples using MALDI-MSI shows differences in the spectral signatures present in healthy skin samples and CL lesion samples, which is evidence of structural and molecular differences in both types of tissue. It is possible to extend this differential analysis by including treatment of CL with topical drugs (for example, pentamidine isethionate, PMD) since the nature of the lesions of CL makes drug treatment difficult by preventing their proper dissemination.…”

Limitations of current chemotherapy and future of nanoformulation-based AmB delivery for visceral leishmaniasis—An updated review

“…In the 1960s, it was revealed that it could kill Leishmania in a dose of 11 mg/kg by intramuscular (IM) treatment for 21 days against VL. Paromomycin works by targeting protein synthesis machinery of the parasite ( Muñoz et al, 2019 ). Paromomycin side effects include pruritus, erythema, discomfort, oedema, ototoxicity, elevated creatinine and transaminases ( Sosa et al, 2013 ; Sundar et al, 2014a ; Sosa et al, 2019 ).…”