Use of topical liposomes containing meglumine antimoniate (Glucantime) for the treatment of L. major lesion in BALB/c mice.
Treatment of cutaneous leishmaniasis (CL) is a dream for the patients, health care authorities and scientists. The aim of this study was to develop a topical liposomal meglumine antimoniate (MA, Glucantime™) (Lip-MA) formulation and evaluate the therapeutic effects of the preparation on lesion induced by Leishmania major in BALB/c mice. Liposomes containing 22.5% MA (6.4% Sb(+5)) with and without oleic acid (LMA-OA and LMA) were formulated using fusion method plus homogenization and characterized for the size and encapsulation efficiency. The penetration of MA from the LMA-OA and LMA formulations through and into the skin was checked in vitro using Franz diffusion cells fitted with mouse skin at 37°C for 8h. The in vitro permeation data showed that almost 1.5% of formulations applied in the mouse skin were penetrated and the amount retained in the skin was about 65%. The 50% effective dose of LMA and LMA-OA against amastigotes of L. major was 46.36 and 41.01 μg/ml, respectively. LMA or LMA-OA was used topically twice a day for 4 weeks to treat the lesion induced by L. major in susceptible BALB/c mice. The results showed a significantly (P<0.001) smaller lesion size in the treated groups of mice compared to the control groups which received either empty liposomes or phosphate-buffered saline (PBS). The spleen parasite burden was significantly (P<0.001) lower in the treated groups compared to the control groups receiving either empty liposomes or PBS at the end of the treatment period. However, when the treatment was stopped, the lesion size progressed and spleen parasite burden increased in LMA and LMA-OA groups, but still was significantly less than the control groups (P<0.05). There was no significant difference between the two formulations of LMA and LMA-OA. The results suggested that topical liposomes containing MA might be an appropriate choice for clinical trials for the treatment of CL.
Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.
S A Moosavian
SA
Kalat
Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.
A
A
Khamesipour
Nanotechnology Research Center, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
N
N
Bavarsad
Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.
M
M
Fallah
Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.
Z
Z
Khashayarmanesh
Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.
E
E
Feizi
Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.
K
K
Neghabi
Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.
A
A
Abbasi
Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran. Electronic address: jafarimr@mums.ac.ir.
M R
MR
Jaafari
D000287:Administration, Topical; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002460:Cell Line; D005260:Female; D018320:Leishmania major / Q000187:drug effects* / Q000254:growth & development; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology; D008536:Meglumine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011897:Random Allocation; D012867:Skin / Q000378:metabolism; D013154:Spleen / Q000469:parasitology
D000981:Antiprotozoal Agents; D008081:Liposomes; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate
Cutaneous leishmaniasis; L. major; Liposome; Meglumine antimoniate (Glucantime™); Topical treatment