Gelatin, a natural polymer, has a number of advantages as a material for fabricating nanoparticles, such as its hydrophilicity, biodegradability, nontoxicity, and biocompatibility, as well as low cost. Despite these various advantages, gelatin-based nanoparticles still have critical limitation for biomedical applications due to their relatively larger size than those of other materials.
In this study, a new strategy to design and fabricate small gelatin nanoparticles (GNPs) was proposed. The technique was based on the natural phenomenon where with decreasing temperature, the compression between the molecules of substances increases and the volume shrinks.
The average size of the fabricated small GNPs was less than 100 nm and their gelatin properties (including non-cytotoxicity) were well maintained. The drug release profiles of the GNPs were confirmed, for which a simple mathematical model based on the conventional diffusion equation was proposed. There was a burst of drug release in the first 3 days, with different release profiles according to the concentration of model drugs loaded onto the GNPs. It was also demonstrated that the drug release profiles of the proposed mathematical model were consistent with the experimental results.
Our work proposes that these small GNPs could be used as efficient drug and gene delivery and tissue engineering platforms for various biomedical applications.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Singh R, Lillard JW Jr. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009;86:215–23.
Hans ML, Lowman AM. Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci. 2002;6:319–27.
Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces. 2010;75:1–18.
Martínez-Díaz GJ, Nelson D, Crone WC, Kao WJ. Mechanical and chemical analysis of gelatin-based hydrogel degradation. Macromol Chem Phys. 2003;204:1898–908.
Wei X, Chen K, Wang Z, Huang B, Wang Y, Yu M, et al. Multifunctional gelatin nanoparticle integrated microchip for enhanced capture, release, and analysis of circulating tumor cells. Part Part Syst Charact. 2019;36:1900076.
Krause HJ, Rohdewald P. Preparation of gelatin nanocapsules and their pharmaceutical characterization. Pharm Res. 1985;2:239–43.
Curcio M, Altimari I, Spizzirri UG, Cirillo G, Vittorio O, Puoci F, et al. Biodegradable gelatin-based nanospheres as pH-responsive drug delivery systems. J Nanopart Res. 2013;15:1–11.
Jahanshahi M, Sanati M, Hajizadeh S, Babaei Z. Gelatin nanoparticle fabrication and optimization of the particle size. Physica Status Solidi. 2008;205:2898–902.
Kaul G, Amiji M. Long-circulating poly (ethylene glycol)-modified gelatin nanoparticles for intracellular delivery. Pharm Res. 2002;19:1061–7.
Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015;33:941–51.
Coester CJ, Langer K, van Briesen H, Kreuter J. Gelatin nanoparticles by two step desolvation a new preparation method, surface modifications and cell uptake. J Microencapsul. 2000;17:187–93.
Raman C, Berkland C, Kim K, Pack DW. Modeling small-molecule release from PLG microspheres: effects of polymer degradation and nonuniform drug distribution. J Control Release. 2005;103:149–58.
Li JK, Wang N, Wu XS. Poly (vinyl alcohol) nanoparticles prepared by freezing-thawing process for protein/peptide drug delivery. J Control Release. 1998;56:117–26.
Beirowski J, Inghelbrecht S, Arien A, Gieseler H. Freeze-drying of nanosuspensions, 1: freezing rate versus formulation design as critical factors to preserve the original particle size distribution. J Pharm Sci. 2011;100:1958–68.
Gorth DJ, Rand DM, Webster TJ. Silver nanoparticle toxicity in Drosophila: size does matter. Int J Nanomedicine. 2011;6:343–50.
Shutava TG, Balkundi SS, Vangala P, Steffan JJ, Bigelow RL, Cardelli JA, et al. Layer-by-layer-coated gelatin nanoparticles as a vehicle for delivery of natural polyphenols. ACS Nano. 2009;3:1877–85.
Cascone MG, Lazzeri L, Carmignani C, Zhu Z. Gelatin nanoparticles produced by a simple W/O emulsion as delivery system for methotrexate. J Mater Sci Mater Med. 2002;13:523–6.
Higuchi T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52:1145–9.
Saraogi GK, Gupta P, Gupta UD, Jain NK, Agrawal GP. Gelatin nanocarriers as potential vectors for effective management of tuberculosis. Int J Pharm. 2010;385:143–9.
Cheng F, Choy YB, Choi H, Kim KK. Modeling of small-molecule release from crosslinked hydrogel microspheres: effect of crosslinking and enzymatic degradation of hydrogel matrix. Int J Pharm. 2011;403:90–5.
Balthasar S, Michaelis K, Dinauer N, von Briesen H, Kreuter J, Langer K. Preparation and characterisation of antibody modified gelatin nanoparticles as drug carrier system for uptake in lymphocytes. Biomaterials. 2005;26:2723–32.
Choy YB, Cheng F, Choi H, Kim KK. Monodisperse gelatin microspheres as a drug delivery vehicle: release profile and effect of crosslinking density. Macromol Biosci. 2008;8:758–65.
This work was also supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through the Agriculture, Food and Rural Affairs Research Center Support Program, funded by the ministry of Agriculture, Food and Rural Affairs (MAFRA) (Project No. 714002) and by the National Research Foundation of Korea (NRF) grant funded by the Korea government under Grant NRF 2021M3E5E703044011 and 2019R1I1A3A01063453. The authors are grateful to the Center for Research Facilities at the Chonnam National University.
Conflicts of interest
The authors declare no conflicts of interest.
There are no animal experiments carried out for this article.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Gwon, Y., Kim, W., Park, S. et al. A Freezing and Thawing Method for Fabrication of Small Gelatin Nanoparticles with Stable Size Distributions for Biomedical Applications. Tissue Eng Regen Med (2021). https://doi.org/10.1007/s13770-021-00380-x
- Small nanoparticle
- Drug release
- Diffusion equation