RES and brain targeting stavudine-loaded solid lipid nanoparticles for AIDS therapy

Panchaxari M Dandagi, Punit D Patel, Anand P Gadad, Anil Kumar Aravapalli


Cells of the reticuloendothelial system (RES, e.g., macrophages) play an important role in the immunopathogenesis of Acquired Immunodeficiency Syndrome (AIDS). The objective of the present study was to investigate the possibility of specifically targeting antiviral drugs Stavudine to RES (like Liver, Spleen etc.) and brain using solid lipid nanoparticles (SLNs) as colloidal drug carriers. Various lipids like stearic acid, cetyl palmitate, glyceryl behenate and phospholipid in combination have been used and effect of lipid on properties of SLNs has been investigated. The SLNs of Stavudine were prepared by double emulsion solvent evaporation method.The diameter of SLNs was determined and found in range of 175 ± 6.027 to 393 ± 2.309 nm depending on the type of lipid used. Percentage drug entrapment was found to be influenced by the concentration and type of lipid used, which was found in the range of 18.1 to 65.2%. The drug release behavior was studied by dialysis bag method and the release pattern of drug was found to follow Higuchi model. Results of stability
evaluation showed a relatively long-term stability after storage at 4°C for 1 month. Stavudine-loaded SLNs were successfully prepared, optimized and effectively targeted to RES and brain. SLNs of Stavudine have been shown to be taken up by brain 11 fold greater as compared to pure Stavudine. This finding is more important since Human Immunodeficiency Syndrome
(HIV) infect the central nervous system.

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Düzgüneş N, Simões S, Slepushkin V, Pretzer E, Flasher D, Salem II,

et al. Delivery of antiviral agents in liposomes. Methods Enzymol


Gendelman HE, Orenstein JM, Baca LM, Weiser B, Burger H, Kalter DC,

et al. The macrophage in the persistence and pathogenesis of HIV

infection. AIDS 1989;3:475-95.

Von Briesen H, Andreesen R, Esser R, Brugger W, Meichsner C,

et al. Infection of monocytes/macrophages by HIV in vitro. Res Virol


Haase AT, Henry K, Zupancic M, Sedgewick G, Faust RU, Melroe H,

et al. Quantitative image analysis of HIV-1 infection in lymphoid tissue.

Science 1996;274:985-9.

Lobenberg R, Kreuter J. Macrophage- targeting of azidothymidine:

A promising strategy for AIDS therapy. AIDS Res Hum Retroviruses


Garg M, Garg BR, Jain S, Mishra P, Sharma RK, Mishra AK, et al.

Radiolabeling, pharmacoscintigraphic evaluation and antiretroviral

efficacy of stavudine loaded 99mTc labeled galactosylated liposomes.

Eur J Pharm Sci 2008;33:271-81

Mallipeddi R, Rohan LC. Progress in antiretroviral drug delivery using

nanotechnology. Int J Nanomedicine 2010;5:533-47.

Mehnert W, Mäder K. Solid lipid nanoparticles: Production,

characterization and applications. Adv Drug Del Rev 2001;47:165-96.

Muller RH, Keck CM. Challenges and solutions for the delivery of biotech

drugs – a review of drug nanocrystal technology and lipid nanoparticles.

J Biotechnol 2004;113:151-70.

Castelli F, Puglia C, Sarpietro MG, Rizza L, Bonina F. Characterization

of indomethacin-loaded lipid nanoparticles by differential scanning

calorimetry. Int J Pharm 2005;304:231-8.

Muller RH, Ruhl D, Runge S, Schulze-Foster K, Mehnert W. Cytotoxicity

of solid lipid nanoparticles as a function of the lipid matrix and the

surfactant. Pharm Res 1997;14:458-462.

Chen R, Zhou J, Tang Q, Lu H, Zhou Q, Zhang L. Poly(ethylene glycol)

modified solid lipid nanoparticles as carriers of doxorubicin for the

treatment of hepatocarcinoma cells, ICON (International Council on

Nanotechnology) Nanoscience 2006;11:225-9.

Kreuter J. Nanoparticulate systems for brain delivery of drugs, Adv

Drug Deliv Rev 2001;47:65-81.

Ravi Kumar MN. Nano and microparticles as controlled drug delivery

devices. J Pharm Pharm Sci 2000;3:234-58.

Riddler SA, Anderson RE, Mellors JW. Antiretrovial activity of stavudine (2′,3′-didehydro-3′-deoxythymidine, D4T). Antiviral Res 1995;


Singh S, Dobhal AK, Jain A, Pandit AK, Chakraborthi S. Formulation

and evaluation of solid lipid nanoparticles of a water soluble drug:

Zidovudine. Chem Pharm Bull (Tokyo) 2010;58:650-655.

Mazumder B, Sarkar MK, Dey S, Roy N. Effect of formulation and

process variables on the characteristics of microspheres of antiviral

drug (stavudine) prepared by oil in oil solvent evaporation technique.

Int J Pharm Pharm Sci 2010;2:53-9.

Samento B, Martins S, Ferreira D, Souto EB. Oral insulin delivery of

solid lipid nanoparticles. Int J Nanomedicine 2007;2:743-9.

Jain P, Mishra A, Yadav SK, Patil UK, Baghel US. Formulation development and characterization of solid lipid nanoparticles containing nimesulide. Int J Drug Deliv Technol 2009;1:24-7.

Mukherjee B, Patra B, Layek B, Mukherjee A. Sustained release of

acyclovir from nano-liposomes and nano-niosomes: An in vitro study.

Int J Nanomedicine 2007;2:213-25.

Wang JX, Sun X, Zhang JR. Enhanced brain targeting by synthesis of

′,5′-dioctanoyl-5-fluoro-2′-deoxyuridine and incorporation into solid

lipid nanoparticles. Eur J Pharm Biopharm 2002;54:285-90.

Escobar Y, Venturelli CR, Escobar-islas E, Hoyo Vadillo C. Pharmacokinetics of stavudine by oral administration to healthy mexican volunteers. Proc West Pharmacol Soc 2003;46:109-10.

Lobenberg R, Araujo L, von Briesen H, Rodgers E, Kreuter J. Body

distribution of azidothymidine bound to hexyl-cynoacrylate

nanoparticles after i.v. injection to rats. J Control Release 1998;


The European agency for the evaluation of medical products. Stability

testing guidelines: Stability testing of new drug substances and

products. London: ICH-Technical coordination, EMEA; 2003. Available

from: [cited on 2005 Dec 20]

Lenaerts V, Nagerlkerke JF, Van Berkel TJ, Couvreur P, Grislain L,

Roland M, et al. In vivo uptake of polyisobutylcyanoacrylate

nanoparticles by the rat liver Kupffer, endothelial and parenchymal

cells. J Pharm Sci 1984;73:980-2.

Benatti U, Giovine M, Damonte G, Gasparini A, Scarfi S, De Flora A,

Azidothymidine homodinucleotide-loaded erythrocytes and bioreactors

for slow delivery of the antiretroviral drug azidothymidine. Biochem

Biophys Res Commun 1996;220:20-5.



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