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Cutaneous leishmaniasis: an innovative idea to explore the topical treatment of skin lesions

iMed.ULisboa/ FFULisboa Research Institute for Medicines/ Faculdade de Farmácia, Universidade de Lisboa
Project classification

Scientific area

3.1 Basic medicine

Discipline(s)

Pharmacology and pharmacy

Project description

Project title

Cutaneous leishmaniasis: an innovative idea to explore the topical treatment of skin lesions

Scientific Coordinator's name:

Manuela Colla Carvalheiro

Scientific Coordinator's e-mail:

mcarvalheiro@ff.ul.pt

Principal R&D Unit:

iMed.UL/FFUL

Other R&D Units involved in the project:

-

Project keyword(s)

Cutaneous leishmaniasis; Trifluralin derivatives; Non-invasive drug delivery systems; Combination therapy

Short abstract and comments

The general aim of the proposal is to establish the relevance of ethosomal systems containing drugs with proven antileishmanial activity for the topical treatment of skin lesions caused by Leishmania parasites. Cutaneous leishmaniasis (CL) is the most common form of a vector-borne infection caused by obligate intracellular Leishmania parasites affecting people in tropical and subtropical regions of the world. The dog is considered the major reservoir of the parasites responsible for the prevalence of canine leishmaniasis (CanL) and for the indirect transmission to humans and other animals. Current treatments are difficult to administer, toxic, expensive, and limited in effectiveness and availability. The topical application of active drugs is an approach of great interest to treat CL skin lesions as it targets the infected tissue preventing the risk of side effects in areas other than the diseased ones. The drugs must be able to reach the Leishmania parasites within the phagolysosome of infected macrophages in the deep dermal layer of the skin. Poor skin penetration is the major problem of dermal and transdermal delivery of most compounds and is due to the stratum corneum (SC), the main barrier of the skin. One strategy to weaken this barrier is the use of vesicular systems to enhance skin penetration of drugs. Ethosomes are soft, malleable colloidal particles composed mainly by phospholipids and ethanol. When dispersed in water they form bilayers which entrap water-soluble molecules in their internal water compartment and water-insoluble ones in their lipid bilayers. As noninvasive delivery systems, ethosomes can enable drugs to reach the deep skin layers creating new opportunities of local therapies for the treatment of CL. The limited number of proven chemotherapeutic agents for CL is another important issue. Trifluralin analogues (TFL-A) are new molecules prepared by hemi-synthetic methods that have been investigated in our lab as new drugs for the treatment of leishmaniasis. The mechanism of action is determined by the specific binding to parasite tubulins that causes an antimitotic activity. Previous work has demonstrated that TFL-A incorporated in liposomes were able to reach the sites of infection (liver and spleen) and proved to be active against different leishmania species in murine models. This proposal aims to develop ethosomal systems with special properties suitable for topical application. Different ethosomal systems will be prepared containing one active TFL-A selected from a previous project and a known active antibiotic; and their therapeutic activity will be evaluated in a murine model of cutaneous leishmaniasis. We expect this approach to be superior to the systemic treatment since, by acting in a localized manner, it will require lower and thus less toxic, drug dosage.

Potential uses/indications

With this proposal we expect to obtain novel effective non-conventional formulations and insights on new strategies for the treatment of cutaneous leishmaniasis. In particular, ethosomal systems with enhanced antiparasitic activity suitable for topical treatment of skin infected lesions. These new systems can be included in a more conventional dosage form for topical application.

Status

Ongoing

Partner Status: Seeking Partners?

Yes

Grant number (QREN, FP7, Eureka, etc)

EXPL/CVT-EPI/0862/2012

Last edited on

2013-11-04 13:48:44

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