Phospholipid microspheres: a novel delivery mode for targeting antileishmanial agent in experimental leishmaniasis.
Novel phospholipid microspheres were prepared from polylactic-co-glycolic acid (PLGA) and phosphatidyl ethanol amine in the molar ratio 1:71, to deliver drugs to macrophages in experimental leishmaniasis. Liposomes, well known as drug carrier systems, made from phosphatidylethanolamine, cholesterol and dicetyl phosphate in the molar ratio 7:2:1, were used as control, in order to compare the efficacies of the two carriers. As such, the membrane fluidity of the two carriers was kept at comparable levels by adjusting chemical composition. Moreover, because of the presence of mannosyl fucosyl receptors on macrophages, attempts were made to target an optically active synthetic compound dihydroindolo [2,3-a] indolizine, an antileishmanial agent, intercalated in both mannose-grafted liposomes and mannose-grafted microspheres. When tested for efficacy in lowering parasite load in the spleen, as well as in reducing the hepatic and renal changes associated with infection, the drug intercalated mannose-grafted microspheres were found to be the most active in comparison to drug intercalated liposomes or to the free drug. Thus, mannose-grafted microspheres may have possible application in the clinics not only in visceral leishmaniasis, but also in other macrophage-associated disorders.
Medda
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Division of Biomembrane, Indian Institute of Chemical Biology, Calcuta 700032, India.
Jaisankar
P
P
Manna
R K
RK
Pal
B
B
Giri
V S
VS
Basu
M K
MK
D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D002784:Cholesterol; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D007212:Indolizines / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D019344:Lactic Acid; D007893:Leishmania donovani / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy*; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008358:Mannose; D008863:Microspheres; D010755:Organophosphates; D010714:Phosphatidylethanolamines; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C478019:3-formyl-5,6-dihydroindolo(2,3-a)indolizine; C478018:5-carbomethoxy-3-formyl-5,6-dihydroindolo(2,3-a)indolizine; D000977:Antiparasitic Agents; D007211:Indoles; D007212:Indolizines; D008081:Liposomes; D010755:Organophosphates; D010714:Phosphatidylethanolamines; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; C002290:dicetylphosphate; D019344:Lactic Acid; D002784:Cholesterol; D008358:Mannose