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Intracellular Delivery of Saquinavir in Biodegradable Polymeric Nanoparticles for HIV/AIDS

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Abstract

Purpose

This study aims at developing poly(ethylene oxide)-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticulate system as an intracellular delivery vehicle for saquinavir, an anti-HIV protease inhibitor.

Materials and Methods

Saquinavir-loaded PEO-PCL nanoparticles were prepared by a solvent displacement process. The formed nanoparticles were characterized for size, surface charge, and surface presence of PEO chains. Cellular uptake and distribution of the nanoparticle was examined in THP-1 human monocyte/macrophage (Mo/Mac) cell line. Intracellular saquinavir concentrations were measured as a function of dose and duration of incubation.

Results

The PEO-PCL nanoparticles had a smooth surface and spherical shape and showed a relatively uniform size distribution with a mean particle diameter of approximately 200 nm. The surface presence of PEO chains was confirmed by an increase in the –C–O–(ether) signature of the C1s spectra in electron spectroscopy for chemical analysis. Rapid cellular uptake of rhodamine-123 encapsulated PEO-PCL nanoparticles was observed in THP-1 cells. Intracellular saquinavir concentrations when administered in the nanoparticle formulation were significantly higher than from aqueous solution.

Conclusions

This study shows that PEO-PCL nanoparticles provide a versatile platform for encapsulation of saquinavir and subsequent intracellular delivery in Mo/Mac cells.

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References

  1. X. Li and W. K. Chan. Transport, metabolism and elimination mechanisms of anti-HIV agents. Adv. Drug Deliv. Rev. 39:81–103 (1999).

    Article  CAS  Google Scholar 

  2. K. Kedzierska and S. M. Crowe. The role of monocytes and macrophages in the pathogenesis of HIV-1 infection. Curr. Med. Chem. 9:1893–1903 (2002).

    Article  CAS  Google Scholar 

  3. S. Gunaseelan, O. Deborah, L. Wan, M. J. Leibowitz, A. B. Rabson, S. Stein, and P. J. Sinko. Synthesis of poly(ethylene glycol)-based saquinavir prodrug conjugates and assessment of release and anti-HIV-1 bioactivity using novel protease inhibition assay. Bioconjug. Chem.15:1322–1333 (2004).

    Article  CAS  Google Scholar 

  4. R. B. Kim. Drug transporters in HIV Therapy. Top HIV Med. 11:136–139 (2003).

    PubMed  Google Scholar 

  5. S. A. Costas Kaparissides, K. Kotti, and S. Chaitidou. Recent advances in novel drug delivery systems. AZojono-Journal of Nanotechnology Online2:1–11 (2006).

    Google Scholar 

  6. R. A. Femia and R. E. Goyette. The science of megestrol acetate delivery: potential to improve outcomes in cachexia. BioDrugs19:179–187 (2005).

    Article  CAS  Google Scholar 

  7. D. K. Sarker. Engineering of nanoemulsions for drug delivery. Curr. Drug. Deliv. 2:297–310 (2005).

    Article  CAS  Google Scholar 

  8. J. Panyam and V. Labhasetwar. Targeting intracellular targets. Curr. Drug. Deliv. 1:235–247 (2004).

    Article  CAS  Google Scholar 

  9. A. V. Kabanov and E. V. Batrakova. New technologies for drug delivery across the blood brain barrier. Curr. Pharm. Des. 10:1355–1363 (2004).

    Article  CAS  Google Scholar 

  10. A. R. Bender, H. von Briesen, J. Kreuter, I. B. Duncan, and H. Rubsamen-Waigmann. Efficiency of nanoparticles as a carrier system for antiviral agents in human immunodeficiency virus-infected human monocytes/macrophages in vitro. Antimicrob. Agents Chemother. 40:1467–1471 (1996).

    Article  CAS  Google Scholar 

  11. H. Boudad, P. Legrand, G. Lebas, M. Cheron, D. Duchene, and G. Ponchel. Combined hydroxypropyl-b-cyclodextrin and poly(alkylcyanoacrylate) nanoparticles intended for oral administration of saquinavir. Int. J. Pharm. 218:113–124 (2001).

    Article  CAS  Google Scholar 

  12. S. Ponsart, J. Coudane, and M. Vert. A novel route to poly(epsilon-caprolactone)-based copolymers via anionic derivatization. Biomacromolecules1:275–281 (2000).

    Article  CAS  Google Scholar 

  13. D. Lemoine, C. Francois, F. Kedzierewicz, V. Preat, M. Hoffman, and P. Maincent. Stability study of nanoparticles of poly (epsilon-caprolactone), poly(d,l-lactide) and poly(d,l-lactide-co-glycolide). Biomaterials17:2191–2197 (1996).

    Article  CAS  Google Scholar 

  14. J. S. Chawla and M. M. Amiji. Biodegradable poly(epsilon-caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen. Int. J. Pharm. 249:127–138 (2002).

    Article  CAS  Google Scholar 

  15. D. B. Shenoy and M. M. Amiji. Poly(ethylene oxide)-modified poly(epsilon-caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer. Int. J. Pharm. 293:261–270 (2005).

    Article  CAS  Google Scholar 

  16. S. Noble and D. Faulds. Saquinavir. A review of its pharmacology and clinical potential in the management of HIV infection. Drugs52:93–112 (1996).

    Article  CAS  Google Scholar 

  17. J. Batsis. Clinical pharmacology of protease inhibitors in HIV infection. Trinity Stud. Med. J. 1:60–65 (2000).

    Google Scholar 

  18. C. Flexner. Dual protease inhibitor therapy in HIV-infected patients: pharmacologic rationale and clinical benefits. Annu. Rev. Pharmacol. Toxicol. 40:649–674 (2000).

    Article  CAS  Google Scholar 

  19. M. T. Huisman, J. W. Smit, H. R. Wiltshire, R. M. Hoetelmans, J. H. Beijnen, and A. H. Schinkel. P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir. Mol. Pharmacol. 59:806–813 (2001).

    Article  CAS  Google Scholar 

  20. A. Bender, A. Immelmann, J. Kreuter, H. Rubsamen-Waigmann, and H. von Briesen. Nanoparticles as drug carriers for antiviral agents against HIV. Int. Conf. AIDS11:64 (1996).

    Google Scholar 

  21. F. Gimenez, C. Fernandez, and A. Mabondzo. Transport of HIV protease inhibitors through the blood–brain barrier and interactions with the efflux proteins, P-glycoprotein and multidrug resistance proteins. J. Acquir. Immune Defic. Syndr. 36:649–658 (2004).

    Article  CAS  Google Scholar 

  22. A. Janoly, N. Bleyzac, P. Favetta, M. C. Gagneu, Y. Bourhis, S. Coudray, I. Oger, and G. Aulagner. Simple and rapid high-performance liquid chromatographic method for nelfinavir, M8 nelfinavir metabolite, ritonavir and saquinavir assay in plasma. J. Chromatogr. B, Analyt. Technol. Biomed. Life Sci. 780:155–160 (2002).

    Article  CAS  Google Scholar 

  23. S. Tsuchiya, M. Yamabe, Y. Yamaguchi, Y. Kobayashi, T. Konno, and K. Tada. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int. J. Cancer 26:171–176 (1980).

    Article  CAS  Google Scholar 

  24. J. S. Chawla and M. M. Amiji. Cellular uptake and concentrations of tamoxifen upon administration in poly (epsilon-caprolactone) nanoparticles. AAPS PharmSciTech 5:E3 (2003).

    Google Scholar 

  25. X. Huang and C. S. Brazel. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J. Control. Release73:121–136 (2001).

    Article  CAS  Google Scholar 

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Acknowledgments

The authors thank Professor Robert Campbell for the access to particle size and zeta potential instrument and Ms. Sushma Kommareddy for the SEM analysis. Additionally, Dr. Lara Gamble’s help with the ESCA investigations at the NESAC/BIO is gratefully acknowledged. NESAC/BIO is supported by the National Institutes of Health grant EB-002027.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, Massachusetts, 02115, USA

    Lipa K. Shah & Mansoor M. Amiji

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  1. Lipa K. Shah
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  2. Mansoor M. Amiji
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Correspondence to Mansoor M. Amiji.

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Shah, L.K., Amiji, M.M. Intracellular Delivery of Saquinavir in Biodegradable Polymeric Nanoparticles for HIV/AIDS. Pharm Res 23, 2638–2645 (2006). https://doi.org/10.1007/s11095-006-9101-7

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  • DOI: https://doi.org/10.1007/s11095-006-9101-7

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