Exploitation of Lectinized Lipo-Polymerosome Encapsulated Amphotericin B to Target Macrophages for Effective Chemotherapy of Visceral Leishmaniasis

被引:22
作者
Gupta, Pramod K. [1 ]
Asthana, Shalini [1 ]
Jaiswal, Anil K. [2 ]
Kumar, Vivek [1 ]
Verma, Ashwni K. [1 ]
Shukla, Prashant [1 ]
Dwivedi, Pankaj [1 ]
Dube, Anuradha [2 ]
Mishra, Prabhat R. [1 ]
机构
[1] CSIR, Cent Drug Res Inst, Lucknow 226031, Uttar Pradesh, India
[2] CSIR, Cent Drug Res Inst, Div Parasitol, Lucknow 226031, Uttar Pradesh, India
关键词
WHEAT-GERM-AGGLUTININ; SIALIC ACIDS; NANOPARTICLES; TOXICITY; BINDING; IDENTIFICATION; FORMULATION; ACTIVATION; MANNOSE;
D O I
10.1021/bc500087h
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We have designed lectin functionalized Lipo-polymerosome bearing Amphotericin B (Lec-AmB-L-Psome) for specific internalization via lectin receptors overexpressed on infected macrophages of mononuclear phagocytic system (MPS) for the effective management of intramacrophage diseases such as visceral leishmaniasis. The lipo-polymerosome composed of glycol chitosan-stearic acid copolymer (GC-SA(25%)) and model lipid cholesterol was surface-functionalized with lectin by the EDC/NHS carbodiimide coupling method. Our designed Lec-AmB-L-Psome showed >2-fold enhanced uptake and significantly higher internalization in macrophages as compared to AmB-L-Psome. Importantly, pharmacokinetic and organ distribution studies illustrate significantly higher accumulation of Lec-AmB-L-Psome in MPS especially in liver, spleen, and lung as compared to AmB-L-Psome, Ambisome, and Fungizone. The IC50 value demonstrated that Lec-AmB-L-Psome has 1.63, 2.23, and 3.43 times higher activity than AmB-L-Psome (p < 0.01), Ambisome (p < 0.05), and Fungizone (p < 0.05), respectively. Additionally, the Lec-AmB-L-Psome showed significantly higher splenic parasite inhibition (78.66 +/- 3.08%) compared to Fungizone and Ambisome that caused only 56.54 +/- 3.91% (p < 0.05) and 66.46 +/- 2.08% (p < 0.05) parasite inhibition, respectively, in Leishmania-infected hamsters. The toxicity profile revealed that Lec-AmB-L-Psome is a safe delivery system with diminished nephrotoxicity which is a limiting factor of Fungizone application. Taken together, these studies suggest that this surface functionalized self-assembled Lec-AmB-L-Psome can introduce a new platform to specifically target macrophages for effective management of intramacrophage diseases.
引用
收藏
页码:1091 / 1102
页数:12
相关论文
共 39 条
[1]   Immunoadjuvant Chemotherapy of Visceral Leishmaniasis in Hamsters Using Amphotericin B-Encapsulated Nanoemulsion Template-Based Chitosan Nanocapsules [J].
Asthana, Shalini ;
Jaiswal, Anil K. ;
Gupta, Pramod K. ;
Pawar, Vivek K. ;
Dube, Anuradha ;
Chourasia, Manish K. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2013, 57 (04) :1714-1722
[2]   Zwitterionic Chitosan Derivative, a New Biocompatible Pharmaceutical Excipient, Prevents Endotoxin-Mediated Cytokine Release [J].
Bajaj, Gaurav ;
Van Alstine, William G. ;
Yeo, Yoon .
PLOS ONE, 2012, 7 (01)
[3]   An invertebrate TNF functional analogue activates macrophages via lectin-saccharide interaction with ion channels [J].
Bilej, Martin ;
Joskova, Radka ;
Van den Bergh, Rafael ;
Prochazkova, Petra ;
Silerova, Marcela ;
Ameloot, Paul ;
De Baetselier, Patrick ;
Beschin, Alain .
INTERNATIONAL IMMUNOLOGY, 2006, 18 (12) :1663-1670
[4]  
Boswell GW, 1998, ANTIMICROB AGENTS CH, V42, P263
[5]   ROLE OF MANNOSE N-ACETYLGLUCOSAMINE RECEPTORS IN BLOOD CLEARANCE AND CELLULAR ATTACHMENT OF LEISHMANIA-DONOVANI [J].
CHAKRABORTY, P ;
DAS, PK .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1988, 28 (01) :55-62
[6]   Identification of sialic acids on Leishmania donovani amastigotes [J].
Chava, AK ;
Chatterjee, M ;
Gerwig, GJ ;
Kamerling, JP ;
Mandal, C .
BIOLOGICAL CHEMISTRY, 2004, 385 (01) :59-66
[7]  
CHRISTIANSEN NP, 1988, BLOOD, V71, P1624
[8]  
Desjardins Philippe, 2009, J Vis Exp, DOI 10.3791/1610
[9]   Drug targeting in cancer therapy: The magic bullet, what next? [J].
Duncan, R ;
Connors, TA ;
Meada, H .
JOURNAL OF DRUG TARGETING, 1996, 3 (05) :317-319
[10]   Comparative pharmacokinetics, tissue distributions, and effects on renal function of novel polymeric formulations of amphotericin B and amphotericin B-deoxycholate in rats [J].
Echevarría, I ;
Barturen, C ;
Renedo, MJ ;
Trocóniz, IF ;
Dios-Viéitez, MC .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2000, 44 (04) :898-904