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Modified Nanoprecipitation Method for Preparation of Cytarabine-Loaded PLGA Nanoparticles

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Abstract

The present investigation was aimed at developing cytarabine-loaded poly(lactide-coglycolide) (PLGA)-based biodegradable nanoparticles by a modified nanoprecipitation which would have sustained release of the drug. Nine batches were prepared as per 32 factorial design to optimize volume of the co-solvent (0.22–0.37 ml) and volume of non-solvent (1.7–3.0 ml). A second 32 factorial design was used for optimization of drug: polymer ratio (1:5) and stirring time (30 min) based on the two responses, mean particle size (125 ± 2.5 nm), and percentage entrapment efficiency (21.8 ± 2.0%) of the Cyt-PLGA nanoparticles. Optimized formulation showed a zeta potential of −29.7 mV indicating good stability; 50% w/w of sucrose in Cyt-PLGA NP was added successfully as cryoprotectant during lyophilization for freeze-dried NPs and showed good dispersibility with minimum increase in their mean particle sizes. The DSC thermograms concluded that in the prepared PLGA NP, the drug was present in the amorphous phase and may have been homogeneously dispersed in the PLGA matrix. In vitro drug release from the pure drug was complete within 2 h, but was sustained up to 24 h from PLGA nanoparticles with Fickian diffusion. Stability studies showed that the developed PLGA NPs should be stored in the freeze-dried state at 2–8°C where they would remain stable in terms of both mean particle size and drug content for 2 months.

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References

  1. Ho DHW, Frei E. Clinical pharmacology of 1-B-D arabinofuranosylcytosine. Clin Pharmacol Ther. 1971;12:944–54.

    CAS  PubMed  Google Scholar 

  2. Knoester PD, Underberg WJM, Beijnen JH. Clinical pharmacokinetics and pharmacodynamics of anticancer agents in pediatric patients. Anticancer Res. 1993;13:1795–808.

    CAS  PubMed  Google Scholar 

  3. Blanco MD, Trigo RM, Teijón C, Gómez C, Teijón JM. Slow releasing of ara-C from poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-N-vinyl-2-pyrrolidone) hydrogels implanted subcutaneously in the back of rats. Biomaterials. 1998;19:861–9.

    Article  CAS  PubMed  Google Scholar 

  4. Ruckmani K, Jayakar B, Ghosal SK. Nonionic surfactant vesicles (Niosomes) of cytarabine hydrochloride for effective treatment of leukemias: encapsulation, storage, and in vitro release. Drug Dev Ind Pharm. 2000;26(2):217–22.

    Article  CAS  PubMed  Google Scholar 

  5. Subramanian N, Yajnik A, Murthy RSR. Artificial neural network as an alternative to multiple regression analysis in optimizing formulation parameters of cytarabine liposomes. AAPS PharmSciTech. 2004;5(1):1–9. Article 4.

    Article  Google Scholar 

  6. Craparo EF, Cavallaro G, Bondì ML, Giammona G. Preparation of polymeric nanoparticles by photo-crosslinking of an acryloylated polyaspartamide in w/o microemulsion. Macromol Chem Phys. 2004;205:1955–64.

    Article  CAS  Google Scholar 

  7. Gómez C, Blanco MD, Bernardo MV, Olmo R, Muñiz E, Teijón JM. Cytarabine release from comatrices of albumin microspheres in a poly(lactide–co- glycolide) film: in vitro and in vivo studies. Eur J Pharm Biopharm. 2004;57:225–33.

    Article  PubMed  Google Scholar 

  8. Gliding DK, Reed AM. Biodegradable polymers for use in surgery: poly(glycolic)/poly (lactic acid) homo and co-polymers. Polymer. 1979;20:1459–64.

    Article  Google Scholar 

  9. Wise DL, Fellmann TD, Sanderson JE, Wentworth RL. Lactic/glycolic acid polymers. In: Gregoridas G, editor. Drug carriers in biology and medicine. London: Academic; 1979. p. 237–70.

    Google Scholar 

  10. Anderson JM, Shive MS. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev. 1997;28:5–24.

    Article  CAS  PubMed  Google Scholar 

  11. Barichello JM, Morishita M, Takayama K, Nagai T. Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method. Drug Dev Ind Pharm. 1999;25(4):471–6.

    Article  CAS  PubMed  Google Scholar 

  12. Bilati U, Allemann E, Doelker E. Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. Eur J Pharm Sci. 2005;24:67–75.

    Article  CAS  PubMed  Google Scholar 

  13. Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm. 1989;55:25–8.

    Article  Google Scholar 

  14. Fessi, H., Devissaguet, J.-P., Puisieux, F., Thies, C. 1992. Process for the preparation of dispersible colloidal systems of a substance in the form of nanoparticles. US Patent 593 522.

  15. Peltonen L, Aitta J, Hyvönen S, Karjalainen M and Hirvonen J. Improved Entrapment Efficiency of Hydrophilic Drug Substance During Nanoprecipitation of Poly(l)lactide Nanoparticles. AAPS PharmSciTech 2004; 5 (1): Article 16.

    Google Scholar 

  16. Yadav KS, Sawant KK. Formulation optimization of etoposide loaded PLGA nanoparticles by double factorial design and their evaluation. Curr Drug Deliv. 2010;7:51–64.

    Article  CAS  PubMed  Google Scholar 

  17. McCarron PA, Woolfson AD, Keating SM. Response surface methodology as a predictive tool for determining the effects of preparation conditions on the physicochemical properties of poly(isobutylcyanoacrylate) nanoparticles. Int J Pharm. 1999;193:37–47.

    Article  CAS  PubMed  Google Scholar 

  18. Freitas, Muller RH. Spray-drying of solid lipid nanoparticles (SLN™). Eur J Pharm Biopharm. 1998;46:145–51.

    Article  CAS  PubMed  Google Scholar 

  19. Levy MY, Benita S. Drug release from submicronized o/w emulsion: a new in vitro kinetic evaluation model. Int J Pharm. 1990;66:29–37.

    Article  CAS  Google Scholar 

  20. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25–35.

    Article  CAS  Google Scholar 

  21. Hocking RR. Analysis and selection of variables in linear regression. Biometrics. 1976;32:1–49.

    Article  Google Scholar 

  22. Montegomery DC. Design and analysis of experiments. New York: Wiley; 2004. p. 392–426.

    Google Scholar 

  23. Chacon M, Molpeceres J, Berges L, Guzman M, Aberturas MR. Stability and freeze-drying of cyclosporine loaded poly(D, L lactide-glycolide) carriers. Eur J Pharm Sci. 1999;8:99–107.

    Article  CAS  PubMed  Google Scholar 

  24. De Chasteigner S, Cave´ G, Fessi H, Devissaguet J-P, Puisieux F. Freeze-drying of itraconazoleloaded nanosphere suspensions: a feasibility study. Drug Dev Res. 1996;38:116–24.

    Article  Google Scholar 

  25. Ahlin P, Kristl J, Kristl A, Vrecer F. Investigation of polymeric nanoparticles as carriers of enalaprilat for oral administration. Int J Pharm. 2002;239:113–20.

    Article  CAS  PubMed  Google Scholar 

  26. Thode K, Muller RH, Kresse M. Two-time window and multiangle photon correlation spectroscopy size and zeta potential analysis-highly sensitive rapid assay for dispersion stability. J Pharm Sci. 2000;89:1317–24.

    Article  CAS  PubMed  Google Scholar 

  27. Kesisoglou F, Panmai S, Wu Y. Nanosizing - Oral formulation development and biopharmaceutical evaluation. Adv Drug Deliv Rev. 2007;59:631–44.

    Article  CAS  PubMed  Google Scholar 

  28. Mandal TK, Bostanian LA, Graves RA, Chapman SR, Womack I. Development of biodegradable microcapsules as carrier for oral controlled delivery of amifostine. Drug Dev Ind Pharm. 2002;28(3):339–44.

    Article  CAS  PubMed  Google Scholar 

  29. Lamprecht A, Ubrich N, Hombreiro Pérez M, Lehr CM, Hoffman M, Maincent P. Influences of process parameters on nanoparticle preparation performed by a double emulsion pressure homogenization technique. Int J Pharm. 2000;196:177–82.

    Article  CAS  PubMed  Google Scholar 

  30. Peppas NA. Analysis of fickian and non-fickian drug release from polymers. Pharm Acta Helv. 1985;60:110.

    CAS  PubMed  Google Scholar 

  31. Dunne M, Corrigan OI, Ramtoola Z. Influence of particle size and dissolution conditions on the degradation properties of polylactide-co-glycolide particles. Biomaterials. 2000;21:1659–68.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Pharmacy Department, TIFAC-Centre of Relevance and Excellence in NDDS, The Maharaja Sayajirao University of Baroda, Fatehgunj, Vadodara, 390002, Gujarat, India

    Khushwant S. Yadav & Krutika K. Sawant

  2. Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, 390001, Gujarat, India

    Krutika K. Sawant

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  1. Khushwant S. Yadav
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Correspondence to Krutika K. Sawant.

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Yadav, K.S., Sawant, K.K. Modified Nanoprecipitation Method for Preparation of Cytarabine-Loaded PLGA Nanoparticles. AAPS PharmSciTech 11, 1456–1465 (2010). https://doi.org/10.1208/s12249-010-9519-4

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