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Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

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Mannan-coated gelatin nanoparticles for sustained and targeted delivery of didanosine: In vitro and in vivo evaluation

Amandeep Kaur1 / Subheet Jain1 / Ashok Tiwary1

Department of Pharmaceutical Sciences, Drug Research Punjabi University, Patiala (Punjab) 147 002, India1

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(CC BY-NC-ND 4.0)

Citation Information: Acta Pharmaceutica. Volume 58, Issue 1, Pages 61–74, ISSN (Online) 1846-9558, ISSN (Print) 1330-0075, DOI: 10.2478/v10007-007-0045-1, March 2008

Publication History:
Published Online:
2008-03-12

Mannan-coated gelatin nanoparticles for sustained and targeted delivery of didanosine: In vitro and in vivo evaluation

Macrophages of the reticuloendothelial system and brain act as major reservoir for HIV because of their long term survival after HIV infection and ability to spread virus particles to bystander CD4 positive lymphocyte cells. The objective of the present study was to investigate mannan-coated nanoparticles for macrophage targeting of didanosine. Different didanosine loaded nanoparticles were prepared using the double desolvation technique and were characterized in vitro, ex vivo and in vivo. Results of the ex vivo cellular uptake study indicated 5--fold higher uptake of didanosine from the mannan-coated nanoparticles formulation (62.5 ± 5.4%) by the macrophages in comparison with didanosine solution in phosphate buffer saline (PBS, pH 7.4) (12.1 ± 2.3%). The better cellular uptake from the nanoparticles formulation was further confirmed by fluorescence microscopy using hydrophilic 6-carboxyfluorescein as a marker. Results of the quantitative biodistribution study showed 1.7, 12.6 and 12.4 times higher localization of didanosine in the spleen, lymph nodes and brain, respectively, after administration of mannan-coated nanoparticles compared to that after injection of didanosine solution in PBS (pH 7.4). Results of the present study showed that the mannan-coated nanoparticles targeted didanosine to the macrophage by mannosyl receptor mediated endocytosis.

Želatinske nanočestice obložene mananom za polaganu i ciljanu isporuku didanozina: In vitro i in vivo vrednovanje

Makrofagi retikuloendotelnog sustava i mozak djeluju kao glavni rezervoari za HIV zbog njihovog dugoročnog preživljavanja nakon infekcije HIV-om i sposobnosti da usmjere virusne čestice u CD4 pozitivne limfocite. Cilj rada bio je ispitati nanočestice obložene mananom za ciljanu isporuku didanozina u makrofage. Koristeći metodu dvostruke desolvatacije pripravljene su različite nanočestice s didanozinom te su zatim karakterizirane in vitro, ex vivo i in vivo. Rezultati ex vivo ispitivanja ukazuju da je unos didanozina u makrofage 5 puta veći iz nanočestica obloženih mananom (62,5 ± 5,4%) u usporedbi s otopinom didanozina u fosfatnom puferu (PBS, pH 7,4) (12,1 ± 2,3%). Bolji celularni unos iz nanočestica potvrđen je fluorescentnom mikroskopijom koristeći hidrofilni 6-karboksifluorescein kao marker. Rezultati kvantitativne biodistribucije pokazuju da je lokalizacija didanozina u slezeni, limfnim čvorovima i mozgu 1,7, 12,6, odnosno 12,4 puta veća nakon primjene nanočestica obloženih mananom nego nakon primjene otopine didanozina u PBS-u (pH 7,4). Nanočestice s mananom usmjeravaju didanozin u makrofage procesom endocitoze u kojoj posreduju receptori za manozu.

Keywords: makrofag; ciljana terapija; didanozin; anti-HIV; manan; endocitoza posredovana receptorima

Keywords: makrofag; ciljana terapija; didanozin; anti-HIV; manan; endocitoza posredovana receptorima

  • M. S. Meltzer, D. R. Skillman, P. J. Gomatos, D. C. Kalter and H. C. Gendelman, Role of mononuclear phagocytosis in the pathogenesis of human immunodeficiency virus infection, Annu. Rev. Immunol.8 (1990)169-194; DOI: 10.1146/annurev.iy.08.040190.001125.[CrossRef]

  • S. Aquaro, R. Calio, J. Balzarini, M. C. Bellocchi, E. Garaci and C. F. Perno, Macrophages and HIV infection: therapeutical approaches toward this strategic virus reservoir, Antiviral Res.55 (2002) 209-225; DOI: 10.1016/S0166-3542(02)00052-9.[CrossRef] [PubMed]

  • C. Oussoren, M. Magnani, A. Fraternale, A. Casabianca, L. Chiarantini, R. Ingebrigsten, W. J. M. Underberg and G. Strome, Liposomes as carrier of the antiretroviral agent dideoxycytidine-5'-triphosphate, Int. J. Pharm.180 (1999) 261-270; DOI: 10.1016/S0378-5173(99)00016-2.[CrossRef]

  • V. Schafer, H. V. Briesen, H. Rubsamen-Waigmann, A. M. Steffan, C. Royer and J. Kreuter, Phagocytosis and degradation of human serum albumin microspheres and nanoparticles in human macrophages, J. Microencaps.11 (1994) 261-269; DOI: 10.3109/02652049409040455.[CrossRef]

  • Z. Cui, C. H. Hsu and R. J. Mumper, Physical characterization and macrophage cell uptake of mannan-coated nanoparticles, Drug Dev. Ind. Pharm.29 (2003) 689-700; DOI: 10.1081/DDC-120021318.[CrossRef] [PubMed]

  • F. Ahsan, I. P. Rivas, M. A. Khan and A. I. T. Suarez, Targeting of macrophage: role of physicochemical properties of particulate carriers-liposomes and microsphere on the phagocytosis by macrophages, J. Control. Rel.79 (2002) 29-40; DOI: 10.1016/S0168-3659(01)00549-1.[CrossRef]

  • J. Kreuter, Nanoparticulate system for brain delivery of drugs, Adv. Drug Deliv. Rev.47 (2001) 65-81; DOI: 10.1016/S0169-409X(00)00122-8.[CrossRef]

  • M. S. Wadhwa and K. G. Rice, Receptor mediated glycotargeting, J. Drug Target.11 (2003) 255-268; DOI: 10.1080/10611860310001636557.[CrossRef]

  • J. Shao and J. K. H. Ma, Characterization of mannosylphospholipid liposome system for drug targeting to alveolar macrophages, J. Drug Deliv. Target. Ther. Agents4 (1997) 43-48.

  • Y. Gabr, N. Assem, A. Micheal and L. Fahmy, Evaluation studies on oxypolygelatin and degraded gelatin as plasma volume expanders, Arzneimittelforschung46 (1996) 763-766.

  • R. Yarchoan, H. Mitsuya, R. V. Thomas, J. M. Pluda, N. R. Hartman and C. F. Perno, In vivo activity against HIV and favorable toxicity profile of 2'3'-dideoxyinosine, Science245 (1989) 412-417.

  • T. P. Cooley, M. L. Kunches, C. A. Saunders, C. J. Perkins, S. L. Kelley, C. McLaren, R. P. McCaffrey and H. A Liebman, Treatment of AIDS and AIDS related complex with 2'3'-dideoxyinosine given once daily, Rev. Infect. Dis.12 (1990) S552-S560.[CrossRef]

  • C. J. Coester, K. Langer, H. Von Briesen and J. Kreuter, Gelatin nanoparticles by two step desolvation - A new preparation method, surface modification and cell uptake, J. Microencaps.17 (2000) 187-193; DOI: 10.1080/026520400288427.[CrossRef]

  • J. Vandervoort and A. Ludwig, Preparation and evaluation of drug-loaded gelatin nanoparticles for topical ophthalmic use, Eur. J. Pharm. Biopharm.57 (2004) 251-261; DOI: 10.1016/S0939-6411(03)00187-5.[CrossRef]

  • E. Rebasamen, W. Goldinger, W. Scheirer, O. W. Merten and G. E. Palfe, Development in Biological Standardization, in Advances in Animal Cell Technology and Cell Engineering: Evaluation and Exploitation (Eds. R. Spier and W. Hennessen), Vol. 66, ESACT, Basel 1987, pp. 557-583.

  • V. F. Courtney, R. C. Brundage, R. P. Remmel, L. M. Page, D. Weller, N. R. Calles, C. Simon and M. W. Kline, Pharmacologic characteristic of indinavir, didanosine and stavudine in human immunodeficiency virus-infected children receiving combination therapy, Antimicrob. Agents Chemother.44 (2000) 1029-1034.

  • S. Jain, R. Sapre, A. K. Tiwary and N. K. Jain, Proultraflexible lipid vesicles for effective transdermal delivery of levonorgestrel: Development, characterization and performance evaluation, AAPS PharmSciTech.6 (2005) E513-E522; DOI: 10.1208/pt060364.[CrossRef]

  • S. Kaul, W. C. Shyu, U. A. Shukla, K. A. Dandekar and R. H. Barbhaiya, Pharmacologic characteristic of indinavir, didanosine and stavudine in human immunodeficiency Virus-Infected children receiving combination therapy, Drug Metab. Dispos.21 (1993) 447-453.

  • E. Mukherji, N. J. Millenbaugh and J. L. S. Au, Percutaneous absorption of 2',3'-dideoxyinosine in rats, Pharm. Res.11 (1994) 809-815.

  • O. Bekers, J. H. Beijnen, M. J. T. Klein Tank, D. M. Burger, P. I. Meenhorst, A. J. P. F. Lombarts and W. J. M. Underberg, 2',3'-dideoxyinosine (ddI): Its chemical stability and cyclodextrin complexation in aqueous media, J. Pharm. Biomed. Anal.11 (1993) 489-493; DOI: 10.1016/0731-7085(93)80162-T.[CrossRef]

  • P. T. Tayade and R. D. Kale, Encapsulation of water-insoluble drug by a cross-linking technique: Effect of process and formulation variables on encapsulation efficiency, particle size, and in vitro dissolution rate, AAPS Pharm. Sci6 (2004); DOI: 10.1208/ps060112.[CrossRef]

  • C. Sanchez-Lafuente, A. M. Rabasco, J. Alvarez-Fuentes and M. Fernandez-Arevalo, Eudragit® RS-PM and Ethocel® 100 premium: influence over the behavior of didanosine inert matrix system, Farmaco57 (2002) 649-656; DOI: 10.1016/S0014-827X(02)01240-5.[CrossRef]

  • V. Apostolopoulos and I. F. McKenzie, Role of the mannose receptor in the immune response, Curr. Mol. Med.1 (2001) 469-474; DOI:10.2174/1566524013363645.[CrossRef]

  • C. A. Hoppe and Y. C. Lee, The binding and processing of mannose-bovine serum albumin derivatives by rabbit alveolar macrophages. Effect of the sugar density, J. Biol. Chem.258 (1983) 14193-14199.

  • M. Velinova, N. Read, C. Kirby and G. Gregoriadis, Morphological observation on the fate of liposomes in the regional lymph nodes after footpad injection into rats, Biochim. Biophys. Acta1299 (1996) 207-215; DOI: 10.1016/0005-2760(95)00208-1.[CrossRef]

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