Topical Treatment Of Cutaneous Leishmaniasis Research Articles

Amphotericin B-Loaded Nanocarriers for Topical Treatment of Cutaneous Leishmaniasis: Development, Characterization, and <I>In Vitro</I> Skin Permeation Studies

Topical treatment of cutaneous leishmaniasis represents an exciting alternative for reducing toxicity associated with parenteral administration of conventional amphotericin B. This work aims to develop and to characterize amphotericin B-loaded new carriers and to investigate their potential for topical delivery by conducting permeation studies with pig ear skin in comparison with marketed formulations. Among other formulations, nanoemulsions were developed and characterized for size, encapsulation efficiency, and zeta potential. To mimic use conditions in topical therapy of cutaneous leishmaniasis, in vitro skin permeation experiments were conducted using a damaged skin model. High encapsulation efficiency (95%) and low particle size (239 nm) were obtained for amphotericin B-loaded nanoemulsion by employing an ion pairing between the drug and stearylamine. Amphotericin B permeation after 24 h across the dermal membrane was low, regardless of the type of formulation tested. In contrast, amphotericin B penetration into dermal membranes (microg/cm2) from solution (control), aqueous Amphocil, hydroalcoholic Amphocil, Fungizone, mixture Fungizone-Lipofundin, and NE was 17.5 +/- 4, 15.2 +/- 3, 9.6 +/- 3, 3.5 +/- 1, 1.7 +/- 0.3, and 1.1 +/- 0.1, respectively. Amphocil provided the best results, highlighted by its high improvement of dermal penetration of amphotericin B.

Efficacy of Topical Liposomal Amphotericin B versus Intralesional Meglumine Antimoniate (Glucantime) in the Treatment of Cutaneous Leishmaniasis

Background. Topical treatment of cutaneous leishmaniasis is an attractive alternative avoiding toxicities of parenteral therapy while being administered through a simple painless route. Recently liposomal formulations of amphotericin B have been increasingly used in the treatment of several types of leishmaniasis. Aims. The efficacy of a topical liposomal amphotericin B formulation was compared with intralesional glucantime in the treatment of cutaneous leishmaniasis. Methods. From 110 patients, the randomly selected 50 received a topical liposomal formulation of amphotericin B into each lesion, 3–7 drops twice daily, according to the lesion's size and for 8 weeks. The other group of 60 patients received intralesional glucantime injection of 1-2 mL once a week for the same period. The clinical responses and side effects of both groups were evaluated weekly during the treatment course. Results. Per-protocol analysis showed no statistically significant difference between the two groups (P = 0.317, 95% confidence interval (CI) = 1.610 (0.632–4.101)). Moreover, after intention-to-treat analysis, the same results were seen (P = 0.650, 95% CI = 0.1.91 (0.560–2.530)). Serious post treatment side effects were not observed in either group. Conclusions. Topical liposomal amphotericin B has the same efficacy as intralesional glucantime in the treatment of cutaneous leishmaniasis.

Topical delivery and in vivo antileishmanial activity of paromomycin-loaded liposomes for treatment of cutaneous leishmaniasis

The present study aimed to evaluate the potential of liposomes loaded with paromomycin (PA), an aminoglycoside antibiotic associated with poor skin penetration, for the topical treatment of cutaneous leishmaniasis (CL). Fluid liposomes were prepared and characterized for particle size, zeta potential, and drug entrapment. Permeation studies were performed with two in vitro models: intact and stripped skin. The antileishmanial activity of free and liposomal PA was evaluated in BALB/c mice infected by Leishmania (L.) major. Drug entrapment ranged from 10 to 14%, and the type of vesicle had little influence on this parameter. Particle size and polydispersity index of the vesicles composed by phosphatidylcholine (PC) and PC/cholesterol (Chol) ranged from of 516 to 362 nm and 0.7 to 0.4, respectively. PA permeation across intact skin was low, regardless of the formulation tested, while drug penetration into skin (percent of the applied dose) from PC (7.2 ± 0.2%) and PC/Chol (4.8 ± 0.2%) liposomes was higher than solution (1.9 ± 0.1%). PA-loaded liposomes enhanced in vitro drug permeation across stripped skin and improved the in vivo antileishmanial activity in experimentally infected mice. Our findings suggest that the liposomes represent a promising alternative for the topical treatment of CL using PA.

Topical morphine for the treatment of cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) is a potentially disfiguring parasitic disease which is endemic in many parts of the world. The evidence for optimal treatment of CL is uncongenial. The development of a compound used for the topical treatment of CL is an attractive option for overcoming the problems of toxic and expensive currently used anti-leishmanial drugs. Easy application is another attraction of topical treatment compared to systemic therapy. Evidence is certainly about a variety of immune responses in the healing process of CL. The immune modulatory effect of morphine also has been known in clinical medicine for decades. Protection against leishmaniasis is dependent upon generation of CD4(+) helper T-cells immune response. There are some evidences that opioids could be members of the cytokine family and the regulation of immune and inflammatory responses is dependent on the functions of cytokines; therefore much effort should be placed on understanding the effect of morphine on cytokine activity. Based on a previous mentioned evidence we suggest that morphine as an immunomodulator could induce the healing process of cutaneous leishmaniasis through inducing the release of a number of cytokines.

Influence of the formulation type (o/w, w/o/w emulsions and ointment) on the topical delivery of paromomycin

Ointments containing paromomycin (PA) have been used for topical treatment of cutaneous leishmaniasis. Although influence of the vehicle on skin permeation is crucial for optimization of formulations containing PA, this aspect has not been investigated experimentally. In this study, we have evaluated the influence of the formulation type [oil-in-water (o/w), water-in-oil-in-water (w/o/w) emulsions and ointment] on in vitro release and skin permeation of PA and experiments were carried out on cellulose acetate membrane and skin biopsies from hairless mice, respectively. PA release from o/w emulsion (51.7% ± 0.9 of dose applied) was faster than that observed for w/o/w emulsion (3.0% ± 0.5). PA absorption from o/w emulsion (87.1% ± 3.9) through stripped skin was 5 to 6 times higher than that observed for w/o/w multiple emulsion (14.7% ± 0.5) and ointment (16.6% ± 0.1). PA permeation through intact (normal) skin was negligible for all tested formulations. Skin uptake from o/w emulsion (0.9% ± 0.1) was greater than that observed for w/o/w multiple emulsion (0.3% ± 0.1) and ointment (0.1% ± 0.1). These results suggest that a hydrophilic vehicle (o/w emulsion) could be an interesting alternative to improve topical delivery of PA.

Transient effect of topical treatment of cutaneous leishmaniasis with imiquimod.

Treatment of cutaneous leishmaniasis can be painful and protracted and cosmetic results are often unsatisfying. The immune modulator imiquimod has been reported to be suitable for the treatment of a variety of infectious skin diseases and neoplasias. We investigated the efficacy of topical application of imiquimod in the treatment of old world leishmaniasis in a placebo-controlled prospective study. Twelve patients were treated with imiquimod cream using a standard protocol, i.e. topical application three times a week, and a further three served as control group. Lesions of cutaneous leishmaniasis regressed within the first 2-4 weeks in 10 of the 12 patients, whereas in two patients no change was observed. However, after 8 weeks all lesions showed progression. Our results thus demonstrate that topical application of imiquimod alone is ineffective in treating old world cutaneous leishmaniasis. Further studies are required to demonstrate a possible benefit of imiquimod in combination with other, preferably orally administered medicines.

Efficient topical treatment for cutaneous leishmaniasis based on amphotericin B

Efficient topical treatment for cutaneous leishmaniasis based on amphotericin B

Topical treatment of cutaneous leishmaniasis in belize: In vitro and in vivo studies with Leishmania mexicana

Strains of Leishmania mexicana isolated from Belizian patients were found to be highly susceptible to paromomycin sulphate (PR) treatment. This drug at 100 μg ml −1 destroyed 85–99.5% of in vitro cultivated Leishmania promastigotes within 4 days of exposure to the drug. Leishmania promastigotes inoculated into the base of the tail of Balb/c mice caused the development of local lesions several weeks after infection. These lesions were totally cleared of parasites after 20 days of topical treatment with PR ointment, comprised of 15% paromomycin sulphate and 12% methylbenzethonium chloride in soft white paraffin. Similar results were also obtained with L. braziliensis infections. Isoenzyme analysis was found to be the method of choice for parasite strain identification. Excreted factor serotyping was only partially effective and promastigote agglutination gave negative results.

Topical Treatment of Cutaneous Leishmaniasis

Sixty-seven patients, 19 females and 48 males, 4-66 years old, suffering from lesions of cutaneous leishmaniasis were treated topically with an ointment comprising 15% paromomycin sulfate and 12% methylbenzethonium chloride in white soft paraffin (P-ointment, U.K. patent GB117237A). After 10 days of treatment, twice daily, the lesions in 72% of the treated patients were free of parasites, 15% became free within an additional 20 days, without further treatment, and 13% failed to respond. Pigmentation developed in 18% of the treated lesions and inflammation of varying degree was associated with the treatment. These developments did not affect the clinical healing process which was generally completed in a period of 10-30 days after termination of treatment. In addition, 94% of the treated lesions healed with little or no scarring. No adverse clinical or laboratory side effects were observed except for a burning sensation at the site of treatment. Parasites isolated from patients who failed to respond to topical treatment were found to be susceptible to PR-MBCl in both in vitro infected macrophages and in vivo in experimentally infected BALB/c mice.

Development of topical treatment for cutaneous leishmaniasis caused by Leishmania major in experimental animals

Topical treatment, with drug-containing ointments, of cutaneous leishmaniasis caused by Leishmania major in BALB/c mice was studied. Twenty chemotherapeutic agents having potential or established antileishmanial activity were formulated in different ointment and cream bases. Only 15% paromomycin sulfate with 12% methylbenzethonium chloride, 12% benzethonium chloride, 12% cetalkonium chloride, or 12% dimethyl sulfoxide, all incorporated in white soft paraffin (United Kingdom patent application no. 2117237A), were completely effective. Topical treatment twice daily for 6 or more days caused total elimination of the parasites and healing of the lesion in all treated mice. All the other antileishmanial compounds, including sodium stibogluconate, pentamidine, amphotericin B, emetine hydrochloride, metronidazole, co-trimoxazole, allopurinol, and rifampin, either showed a slight effect on the parasites or were highly toxic to the animal host at the concentrations tested.