Paromomycin Sulfate

Paromomycin Sulfate is an aminoglycoside antibioticis inhibiting protein synthesis in non-resistant cells by binding to 16S ribosomal RNA.

Colloidal, in vitro and in vivo anti-leishmanial properties of transfersomes containing paromomycin sulfate in susceptible BALB/c mice.[Pubmed:22750480]

Acta Trop. 2012 Oct;124(1):33-41.

The aim of this study was to develop transfersomal formulation with respect to dermal delivery of Paromomycin Sulfate (PM) for possible topical therapy of cutaneous leishmaniasis (CL). PM transfersomal formulations (PMTFs) with different percent of soy phosphatidylcholine, sodium cholate (Na-Ch) and ethanol were prepared and characterized for the size, zeta potential and encapsulation efficiency. The results showed that the most stable formulations with suitable colloidal properties were obtained by 2% Na-Ch which had average size of around 200 nm. The in vitro permeation study using Franz diffusion cells fitted with mouse skin at 37 degrees C for 24h showed that almost 23% of the PMTFs applied penetrated the mouse skin, and the amount retained in the skin was about 67% for both formulations; however, the percent of penetration and retention for PM conventional cream was 49 and 13, respectively. The 50% effective doses of PMTFs against Leishmania major promastigotes and amastigotes in culture were significantly less than cream and/or solution of PM. Selected PMTFs and empty transfersomes showed no cytotoxicity in J774 A.1 mouse macrophage cell line. Selected PMTFs was used topically twice a day for 4 weeks to treat L. major lesions on BALB/c mice, and the results showed a significantly (P<0.05) smaller lesion size in the mice in the treated groups than in the mice in the control groups, which received either empty transfersomes or phosphate-buffered saline (PBS) and also PM cream. The spleen parasite burden was significantly (P<0.01) lower in mice treated with selected PMTFs than in mice treated with PBS or control transfersomes, and PM cream. The results of this study showed that PMTFs prepared with 2% of Na-Ch with and without 5% ethanol might be useful as a candidate for the topical treatment of CL.

Characterization of the binding of neomycin/paromomycin sulfate with DNA using acridine orange as fluorescence probe and molecular docking technique.[Pubmed:27392082]

J Biomol Struct Dyn. 2017 Aug;35(10):2077-2089.

The binding of neomycin sulfate (NS)/Paromomycin Sulfate (PS) with DNA was investigated by fluorescence quenching using acridine orange (AO) as a fluorescence probe. Fluorescence lifetime, FT-IR, circular dichroism (CD), relative viscosity, ionic strength, DNA melting temperature, and molecular docking were performed to explore the binding mechanism. The binding constant of NS/PS and DNA was 6.70 x 10(3)/1.44 x 10(3) L mol(-1) at 291 K. The values of DeltaH(theta), DeltaS(theta), and DeltaG(theta) suggested that van der Waals force or hydrogen bond might be the main binding force between NS/PS and DNA. The results of Stern-Volmer plots and fluorescence lifetime measurements all revealed that NS/PS quenching the fluorescence of DNA-AO was static in nature. FT-IR indicated that the interaction between DNA and NS/PS did occur. The relative viscosity and melting temperature of DNA were almost unchanged when NS/PS was introduced to the solution. The fluorescence intensity of NS/PS-DNA-AO was decreased with the increase in the ionic strength. For CD spectra of DNA, the intensity of positive band at nearly 275 nm was decreased and that of negative band at nearly 245 nm was increased with the increase in the concentration of NS/PS. The binding constant of NS/PS with double-stranded DNA (dsDNA) was larger than that of NS/PS with single-stranded DNA (ssDNA). From these studies, the binding mode of NS/PS with DNA was evaluated to be groove binding. The results of molecular docking further indicated that NS/PS could enter into the minor groove in the A-T rich region of DNA.

Effect of topical liposomes containing paromomycin sulfate in the course of Leishmania major infection in susceptible BALB/c mice.[Pubmed:19223613]

Antimicrob Agents Chemother. 2009 Jun;53(6):2259-65.

The aim of this study was to evaluate the antileishmanial effects of topical liposomal Paromomycin Sulfate (PM) in Leishmania major-infected BALB/c mice. Liposomes containing 10 or 15% PM (Lip-PM-10 and Lip-PM-15, respectively) were prepared by the fusion method and were characterized for their size and encapsulation efficiency. The penetration of PM from the liposomal PM formulations (LPMFs) through and into skin was evaluated in vitro with Franz diffusion cells fitted with mouse skin at 37 degrees C for 8 h. The in vitro permeation data showed that almost 15% of the LPMFs applied penetrated the mouse skin, and the amount retained in the skin was about 60% for both formulations. The 50% effective doses of Lip-PM-10 and Lip-PM-15 against L. major promastigotes in culture were 65.32 and 59.73 microg/ml, respectively, and those against L. major amastigotes in macrophages were 24.64 and 26.44 microg/ml, respectively. Lip-PM-10 or Lip-PM-15 was used topically twice a day for 4 weeks to treat L. major lesions on BALB/c mice, and the results showed a significantly (P < 0.001) smaller lesion size in the mice in the treated groups than in the mice in the control group, which received either empty liposomes or phosphate-buffered saline (PBS). Eight weeks after the beginning of the treatment, every mouse treated with LPMFs was completely cured. The spleen parasite burden was significantly (P < 0.001) lower in mice treated with Lip-PM-10 or Lip-PM-15 than in mice treated with PBS or control liposomes, but no significant difference was seen between the two groups treated with either Lip-PM-10 or Lip-PM-15. The results suggest that topical liposomal PM may be useful for the treatment of cutaneous leishmaniasis.

Leishmanicidal Activity of Films Containing Paromomycin and Gentamicin Sulfate both In Vitro and In Vivo.[Pubmed:22347298]

Iran J Parasitol. 2011 Aug;6(3):60-5.

BACKGROUND: Based on the efficacy of paromomycin ointment and recent ongoing clinical trials of combination of paromomycin and gentamicin, a new physical form of films of the paromomycin and gentamicin was prepared and anti-Leishmania activities of the prepared films were assessed in vitro and in vivo. METHODS: Paromomycin 15% and gentamicin 0.5% was incorporated in a film using ethyl cellulose and HPMC (Hydroxyl Propyl Methyl Cellulose). In order to assess the drug release and anti-Leishmania activities of the preparation, a clone L. major parasite was established using a set of modified NNN medium without overlay liquid layer. Therapeutic effects of the films were evaluated using Balb/c mice model. The mice were inoculated with 2x10(6)L. major promastigotes (MRHO/IR/75/ER) and then when the lesions developed the mice were randomly divided in 3 groups, 10 mice per group, and treated with either perpetrated films or placebo for 28 days or left untreated. RESULTS: Growth inhibition of cloned promastigotes showed that the films have enough releasing capacity and in vivo system, the films containing paromomycin and gentamicin was able to reduce the lesion size and induced complete cure in 80% of the mice but relapse was seen in 60% of the cured mice and overall 50% cure rate was seen during 20 weeks period of the study. CONCLUSION: It seems that the prepared films might be further used in human clinical trials.