Preparation of protein-loaded PLGA-PVP blend nanoparticles by nanoprecipitation method: entrapment, Initial burst and drug release kinetic studies

Document Type: Research Paper

Authors

1 Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran

2 Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

3 Department of Chemistry and Industrial Chemistry, University of Pisa, Via Risorgimento 35, 56126 Pisa, Italy

10.7508/nmj.2015.03.002

Abstract

Objective(s):
Despite of wide range applications of polymeric nanoparticles in protein delivery, there are some problems for the field of protein entrapment, initial burst and controlled release profile.  
Materials and Methods:
In this study, we investigated the influence of some changes in PLGA nanoparticles formulation to improve the initial and controlled release profile. Selected parameters were: pluronic F127, polysorbate 80 as surfactant, pH of inner aqueous phase, L/G ratio of PLGA polymer, volume of inner aqueous phase and addition of polyvinylpyrrolidone as an excipient. FITC-HSA was used as a model hydrophilic drug. The nanoparticles were prepared by nanoprecipitation.  
Results: 
Initial release of FITC-HSA from PLGA-tween 80 nanoparticles (opt-4, 61%) was faster than control (PLGA-pluronic) after 2.30 h of incubation. Results showed that decrease in pH of inner aqueous phase to pI of protein can decrease IBR but the release profile of protein is the same as control. Release profile with three phases including a) initial burst b) plateau and c) final release phase was observed when we changed volume of inner aqueous phase and L/G ratio in formulation. Co-entrapment of HSA with PVP and pluronic reduced the IBR and controlled release profile in opt-19. Encapsulation efficiency was more than 97% and nanoparticles size and zeta potentials were mono-modal and -18.99 mV, respectively.
 
Conclusion: 
In this research, we optimized a process for preparation of PLGA-PVP-pluronic nanoparticles of diameter less than 300 nm using nanoprecipitation method. This formulation showed a decreased initial burst and long lasting controlled release profile for FITC-HSA as a model drug for proteins.

Keywords


1. Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev. 2003; 55(3): 329-47.

2. Feng SS, Mu L, Win KY, Huang G. Nanoparticles of biodegradable polymers for clinical administration of paclitaxel. Curr Med Chem. 2004; 11(4): 413-24.

3. Feng SS. Nanoparticles of biodegradable polymers for cancer treatment. Biomaterials. 2008; 29(30): 4146-7.

4. Gomes AJ, Lunardi CN, Tedesco AC. Characterization of biodegradable poly(D,L-lactide-co-glycolide) nanoparticles loaded with bacteriochlorophyll-a for photodynamic therapy. Photomed Laser Surg. 2007; 25(5): 428-35.

5. Lecaroz C, Gamazo C, Renedo MJ, Blanco-Prieto MJ. Biodegradable micro- and nanoparticles as long-term delivery vehicles for gentamicin. J Microencapsul. 2006; 23(7): 782-92.

6. Sanchez A, Tobio M, Gonzalez L, Fabra A, Alonso MJ. Biodegradable micro- and nanoparticles as long-term delivery vehicles for interferon-alpha. Eur J Pharm Sci. 2003; 18(3-4): 221-9.

7. Yoo HS, Oh JE, Lee KH, Park TG. Biodegradable nanoparticles containing doxorubicin-PLGA conjugate for sustained release. Pharm Res. 1999; 16(7): 1114-8.

8. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release. 2001; 70(1-2): 1-20.

9. Bala I, Hariharan S, Kumar MN. PLGA nanoparticles in drug delivery: the state of the art. Crit Rev Ther Drug Carrier Syst. 2004; 21(5): 387-422.

10. D'Angelo I, Garcia-Fuentes M, Parajo Y, Welle A, Vantus T, Horvath A, et al. Nanoparticles Based on PLGA:Poloxamer Blends for the Delivery of Proangiogenic Growth Factors. Mol Pharm. 2010; 7(5): 1724-1733.

11. Vroman I, Tighzert L. Biodegradable polymers Materials. 2009; 2: 307-44.

12. Xu P, Gullotti E, Tong L, Highley CB, Errabelli DR, Hasan T, et al. Intracellular drug delivery by poly(lactic-co-glycolic acid) nanoparticles, revisited. Mol Pharm. 2009; 6(1): 190-201.

13. Chiellini F, Piras AM, Errico C, Chiellini E. Micro/nanostructured polymeric systems for biomedical and pharmaceutical applications. Nanomedicine (Lond). 2008; 3(3): 367-93.

14. Wang YC, Wu YT, Huang HY, Yang CS. Surfactant-free formulation of poly(lactic/glycolic) acid nanoparticles encapsulating functional polypeptide: a technical note. AAPS PharmSciTech. 2009; 10(4): 1263-7.

15. Malik DK, Baboota S, Ahuja A, Hasan S, Ali J. Recent advances in protein and peptide drug delivery systems. Curr Drug Deliv. 2007; 4(2): 141-51.

16. Balasubramanian V, Onaca O, Enea R, Hughes DW, Palivan CG. Protein delivery: from conventional drug delivery carriers to polymeric nanoreactors. Expert Opin Drug Deliv. 2010; 7(1): 63-78.

17. Brown LR. Commercial challenges of protein drug delivery. Expert Opin Drug Deliv. 2005; 2(1): 29-42.

18. Van der Walle CF, Sharma G, Ravi Kumar M. Current approaches to stabilising and analysing proteins during microencapsulation in PLGA. Expert Opin Drug Deliv. 2009; 6(2): 177-86.

19. Chan JM, Zhang L, Yuet KP, Liao G, Rhee JW, Langer R, et al. PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery. Biomaterials. 2009; 30(8): 1627-34.

20. Le Garrec D, Gori S, Luo L, Lessard D, Smith DC, Yessine MA, et al. Poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) as a new polymeric solubilizer for hydrophobic anticancer drugs: in vitro and in vivo evaluation. J Control Release. 2004; 99(1): 83-101.

21. Roninson BV, Sullivan FM, Borzelleca JF, Schwartz SL. PVP: a critical review of the kinetics and toxicology of polyvinylpyrrolidone (Povidone). Michigan: Lewis Publishers; 1990.

22. Bharali DJ, Sahoo SK, Mozumdar S, Maitra A. Cross-linked polyvinylpyrrolidone nanoparticles: a potential carrier for hydrophilic drugs. J Colloid Interface Sci. 2003; 258(2): 415-23.

23. Saxena A, Mozumdar S, Johri AK. Ultra-low sized cross-linked polyvinylpyrrolidone nanoparticles as non-viral vectors for in vivo gene delivery. Biomaterials. 2006; 27(32): 5596-602.

24. Charvalos E, Tzatzarakis MN, Van Bambeke F, Tulkens PM, Tsatsakis AM, Tzanakakis GN, et al. Water-soluble amphotericin B-polyvinylpyrrolidone complexes with maintained antifungal activity against Candida spp. and Aspergillus spp. and reduced haemolytic and cytotoxic effects. J Antimicrob Chemother. 2006; 57(2): 236-44.

25. Santander-Ortega MJ, Csaba N, González L, Bastos-González D, Ortega-Vinuesa JL, Alonso MJ. Protein-loaded PLGA–PEO blend nanoparticles: encapsulation, release and degradation characteristics. Colloid Polym Sci. 2010; 288(2): 141-50.

26. Chavanpatil MD, Khdair A, Patil Y, Handa H, Mao G, Panyam J. Polymer-surfactant nanoparticles for sustained release of water-soluble drugs. J Pharm Sci. 2007; 96(12): 3379-89.

27. Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 1999; 79(4):1283-316.

28. Zhu X, Komiya H, Chirino A, Faham S, Fox GM, Arakawa T, et al. Three-dimensional structures of acidic and basic fibroblast growth factors. Science. 1991; 251(4989): 90-3.

29. Csaba N, Gonzalez L, Sanchez A, Alonso MJ. Design and characterisation of new nanoparticulate polymer blends for drug delivery. J Biomater Sci Polym Ed. 2004;15(9): 1137-51.

30. Csaba N, Caamano P, Sanchez A, Dominguez F, Alonso MJ. PLGA:poloxamer and PLGA:poloxamine blend nanoparticles: new carriers for gene delivery. Biomacromolecules. 2005; 6(1): 271-8.

31. Blanco D, Alonso MJ. Protein encapsulation and release from poly(lactide-co-glycolide) microspheres: effect of the protein and polymer properties and of the co-encapsulation of surfactants. Eur J Pharm Biopharm. 1998; 45(3): 285-94.

32. Wang W. Instability, stabilization, and formulation of liquid protein pharmaceuticals. Int J Pharm. 1999; 185(2): 129-88.

33. Rajapaksa TE, Lo DD. Microencapsulation of vaccine antigens and adjuvants for mucosal targeting. Curr. Immunol. Rev., 2010;6: 29-37.

34. Cohen S, Alonso MJ, Langer R. Novel approaches to controlled-release antigen delivery. Int J Technol Assess Health Care. 1994; 10(1): 121-30.

35. Jalil R, Nixon JR. Biodegradable poly(lactic acid) and poly(lactide-co-glycolide) microcapsules: problems associated with preparative techniques and release properties. J Microencapsul. 1990; 7(3): 297-325.

36. Coombes AG, Yeh MK, Lavelle EC, Davis SS. The control of protein release from poly(DL-lactide co-glycolide) microparticles by variation of the external aqueous phase surfactant in the water-in oil-in water method. J Control Release. 1998; 52(3):311-20.

37. Robinson S, Williams PA. Inhibition of protein adsorption onto silica by polyvinylpyrrolidone. Langmuir. 2002; 18(23): 8743–8.

38. Men’shikova AY, Skurkis YO, Evseeva TG, Shkarubskaya ZP, Tennikova TB, Ivanchev SS. Binding of protein to polystyrene particles in the presence of polyvinylpyrrolidone in the surface layer. Russ. J. Appl. Chem/, 2004; 77(12):2011-6.

39. Lee J. Intrinsic adhesion properties of poly(vinyl pyrrolidone) to pharmaceutical materials: humidity effect. Macromol Biosci. 2005; 5(11): 1085-93.

40. Tsunoda S, Kamada H, Yamamoto Y, Ishikawa T, Matsui J, Koizumi K, et al. Molecular design of polyvinylpyrrolidone-conjugated interleukin-6 for enhancement of in vivo thrombopoietic activity in mice. J Control Release. 2000; 68(3): 335-41.

41. Yamamoto Y, Tsutsumi Y, Yoshioka Y, Kamada H, Sato-Kamada K, Okamoto T, et al. Poly(vinylpyrrolidone-co-dimethyl maleic acid) as a novel renal targeting carrier. J Control Release. 2004; 95(2): 229-37.

42. Abe Y, Shibata H, Kamada H, Tsunoda S, Tsutsumi Y, Nakagawa S. Promotion of optimized protein therapy by bioconjugation as a polymeric DDS. Anticancer Agents Med Chem. 2006; 6(3): 251-8.

43. Kamada H, Tsutsumi Y, Sato-Kamada K, Yamamoto Y, Yoshioka Y, Okamoto T, et al. Synthesis of a poly(vinylpyrrolidone-co-dimethyl maleic anhydride) co-polymer and its application for renal drug targeting. Nat Biotechnol. 2003; 21(4): 399-404.

44. D'Souza AJ, Schowen RL, Topp EM. Polyvinylpyrrolidone-drug conjugate: synthesis and release mechanism. J Control Release. 2004; 94(1): 91-100.

45. Mumper RJ, Duguid JG, Anwer K, Barron MK, Nitta H, Rolland AP. Polyvinyl derivatives as novel interactive polymers for controlled gene delivery to muscle. Pharm Res. 1996; 13(5):7 01-9.