Design of gelatin biodegradable nano particles as a carrier system for hydrophilic macromolecules/proteins using nano precipitation technique: A resourceful approach for drug delivery

  • Heidi Mohamed Abdel-Mageed Molecular Biology Department, Genetic Engineering and Biotechnology Division, National Research Centre, Cairo, Egypt
Keywords: Gelatin, nano particles, nano precipitation, bovine serum albumin, hydrophilic drug delivery, protein delivery

Abstract

The objective of this study was to design and optimize formulation of biodegradable and biocompatible gelatin nano particle (GNP) using nano-preciptation technique, as potential delivery systems for hydrophilic macromolecules/proteins using bovine serum albumin (BSA) as a model drug. Various parameters were studied, including the concentration of stabilizer, concentration of gelatin, effect of non-solvent nature and the solvent/non-solvent volume ratio. The robustness of the modified methodology was investigated and the prepared GNP was characterized with respect to particle size, PDI using Zetasizer and morphology using Scanning Electron Microscope (SEM). Results showed that among the tested surfactants, poloxamers were able to stabilize the GNP with a minimum concentration of 7% to prepare stable nano particles in the size range 180–240 nm.  n-butanol, ethyl ether, acetone and acetonitrile did not allow GNP formation, while on using methanol and ethanol, stable GNP was produced. Increasing the polymer concentration above 25mg/ml greatly increased medium viscosity and caused agglomeration. An optimized formulation (20 mg/ml gelatin, 2% BSA, 7% poloxamer 407 and using ethanol as non-solvent) was prepared with 88% entrapment efficiency (EE %). SEM images showed spherical GNP where, loading BSA did not affect GNP morphology.  The cumulative release of BSA after 72 hours was equivalent to 80%. Storage study indicated physical stability GNP after storage at different temperatures for 60 days. The results presented in this study demonstrate and highlight the unexplored potentials of the nano precipitation method for the preparation of nano particles from hydrophilic gelatin polymer for sustained delivery of protein drugs.

Downloads

Download data is not yet available.

References

Allemann E., Leroux J.C., Gurny R. 1998. Polymeric nano-microparticles for theoral delivery of peptides and peptidomimetics, Adv. Drug Deliv Rev. 34171–189.
Azimi B, Nourpanah P, Rabiee M, Arbab S. 2014. Producing Gelatin Nanoparticles as Delivery System for Bovine Serum Albumin. Iran Biomed J.;18(1):34.
Barbosa O., Ortiz C., Berenguer-Murcia A., Torres R., Rodrigues R., Fernandez-Lafuente R. 2014. Glutaraldehyde in bio-catalysts design: a useful crosslinker and a versatile tool in enzyme immobilization. RSC Adv.,4, 1583–1600.
Bilati U., Allemann E., Doelker E., 2005. Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles Eur. J. Pharmaceut. Sci., 24, 67. DOI:10.1016/j.ejps.2004.09.011
Brennan, M., Clarke, S., 1993. Spontaneous degradation of polypeptides at aspartyl and asparaginyl residues: effects of the solvent dielectric. Protein Sci. 2, 331–338
Chakraborty C, Pal S, Doss GP, Wen ZH, Lin CS. 2013. Nanoparticles as 'smart' pharmaceutical delivery. Front Biosci . 1;18:1030-50.
Elzoghby A.O. 2013. Gelatin-based nanoparticles as drug and gene delivery systems: reviewing three decades of research. J Control Release. 28;172(3):1075-1091. doi: 10.1016/j.jconrel.2013.09.019.
Fasano A, Uzzau S. 1997. Modulation of intestinal tight junctions by Zonula occludens toxin permits enteral administration of insulin and other macromolecules in an animal model. J Clin Invest.99(6):1158–1164. doi: 10.1172/JCI119271.
Fathollahipour S., Ghaee A., Mehrizi A., Koosha M. 2016. Controlled Antibiotic Delivery by Gelatin Nanospheres: Optimization, Characterization and Antibacterial Evaluation. J Nanostruct 6(4): 285-292.
Galindo-Rodriguez S., Allemann E., Fessi H., Doelker E. 2004. Physicochemical parameters associated with nanoparticle formation in the salting-out, emulsification-diffusion, and nanoprecipitation methods. Pharm. Res., 21, 1428-1439.
Ganachaud F., Katz J.L., (2005). Nanoparticles and nanocapsules created using theouzo effect: Spontaneous emulsification as an alternative to ultrasonic andhigh-shear devices, Chem. Phys. Chem. 6; 209–216.
Gordon Still J. 2002. Development of oral insulin: progress and current status. Diabetes Metab Res Rev.18(Suppl 1):S29–37. doi:10.1002/dmrr.207.
Guerrero D. Q., Allamann E., Fessi H., Doelker E. 1998. Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers Drug Dev. Ind. Pharm., 24, 1113-1128. DOI: 10.3109/03639049809108571
Gupta A., Bohidar H. 2009. Kinetics of Protein−Protein Complex Coacervation and Biphasic Release of Salbutamol Sulfate from Coacervate Matrix Biomacromolecules, 125, 054904.
Hans M, Lowman A. 2002. Biodegradable nanoparticles for drug delivery and targeting. Curr. Opin. Solid State Mater. Sci., 6, 319–327.
Hornig S., Heinze T., Becer C. R., Schubert U. S. 2009. Synthetic polymeric nanoparticles by nanoprecipitation J. Mater. Chem. 19, 3838-3840.
Kaul G., Amiji M. 2002. Long-Circulating Poly(Ethylene Glycol)-Modified Gelatin Nanoparticles for Intracellular Delivery. Pharmac Res., 19, 1061-1067.
Kavimandan NJ, Losi E, Peppas NA. 2006. Novel delivery system based on complexation hydrogels as delivery vehicles for insulin-transferrin conjugates. Biomaterials.27(20):3846–3854. doi: 10.1016/j.biomaterials.2006.02.026.
Khan A., Schneider M. (2013). Improvement of Nanoprecipitation Technique for Preparation of Gelatin Nanoparticles and Potential Macromolecular Drug Loading. Macromol. Biosci., 13, 455–463.
Lee E. J., Khan S. A., Lim K.-H. Gelatin nanoparticle preparation by nanoprecipitation. J Biomater. Sci.: Polym. Ed. 2013, 22, 753-771.
Marschutz MK, Caliceti P, Bernkop-Schnurch A. 2006. Design and in vivo evaluation of an oral delivery system for insulin. Pharm Res.17(12):1468–1474. doi: 10.1023/A:1007696723125.
Mirzaeia H., Darroudi M. 2017. Zinc oxide nanoparticles: Biological synthesis and biomedical applications. Ceramics Int., 43; 907-914
Musabayane CT, Munjeri O, Bwititi P, Osim EE. 2000. Orally administered, insulin-loaded amidated pectin hydrogel beads sustain plasma concentrations of insulin in streptozotocin-diabetic rats. J Endocrinol.164(1):1–6.
Nam G, Rangasamy S, Purushothaman B, et al. 2015. The application of bactericidal silver nanoparticles in wound treatment. Nanomater Nanotechnol.5:23-28.
O’Hagan DT.1996. The intestinal uptake of particles and the implications for drug and antigen delivery. J Anat.;189:477–482
Pulat M., Akalin G. (2013) Preparation and characterization of gelatin hydrogel support for immobilization of CandidaRugosa lipase, Artificial Cells, Nanomedicine, and Biotechnology, 41:3, 145-151, DOI: 10.3109/10731199.2012.696070
Qazvini N., Zinatloo S., 2011. Synthesis and characterization of gelatin nanoparticles using CDI/NHS as a non-toxic cross-linking system. J. Mater. Sci.: Mater. Med., 22, 63.
Sahoo N., Ku R., Biswas S., Guha A., Kuotsu K. 2015. Recent advancement of gelatin nanoparticles in drug and vaccine delivery. Int J Biol Macromol, 81; 317–331
Santoro M, Tatara AM, Mikos AG. 2014. Gelatin carriers for drug and cell delivery in tissue engineering. J. Control. Release, 190, 210–218.
Sarkar D. 2013. Fabrication of an optimized fluorescer encapsulated polymercoated gelatin nanoparticle and study of its retarded release properties, J.Photochem. Photobiol. 252; 194–202.
Sharma G., Sharma A., Nam J-K, Doss G., Lee S-S. 2015.Nanoparticle based insulin delivery system: the next generation efficient therapy for Type 1 diabetes. J Nanobiotechnology. 13: 74. doi: 10.1186/s12951-015-0136-y
Simone E., Dziubla T., Shuvaev V., Muzykantov V. 2010.Synthesis and Characterization of Polymer Nanocarriers for the Targeted Delivery of Therapeutic Enzymes. Methods Mol Biol. 610: 145–164. doi:10.1007/978-1-60327-029-8_9.
Uchida T, Toida Y, Sakakibara S, Miyanaga Y, Tanaka H, Nishikata M, et al. 2001. Preparation and characterization of insulin-loaded acrylic hydrogels containing absorption enhancers. Chem Pharm Bull 49(10):1261–1266. doi: 10.1248/cpb.49.1261.
Yamamoto A, Taniguchi T, Rikyuu K, Tsuji T, Fujita T, Murakami M, et al. 1994. Effects of various protease inhibitors on the intestinal absorption and degradation of insulin in rats. Pharm Res.11(10):1496–1500. doi: 10.1023/A:1018968611962.
Yasmin R., Shaha M., Khan S., Ali R. 2017. Gelatin nanoparticles: a potential candidate for medical applications. Nanotechnol Rev ; 6(2): 191–207. DOI 10.1515/ntrev-2016-0009
Zwiorek K, Kloeckner J, Wagner E, Coester C. 2005. Gelatin nanoparticles as a new and simple gene delivery system. J Pharm Pharm Sci. 3;7(4):22-28.
Published
2017-11-30
How to Cite
Abdel-Mageed, H. M. (2017). Design of gelatin biodegradable nano particles as a carrier system for hydrophilic macromolecules/proteins using nano precipitation technique: A resourceful approach for drug delivery. IJRDO - JOURNAL OF BIOLOGICAL SCIENCE, 3(11), 59-72. https://doi.org/10.53555/bs.v3i11.3025