Recent advancement of gelatin nanoparticles in drug and vaccine delivery

https://doi.org/10.1016/j.ijbiomac.2015.08.006Get rights and content

Abstract

Novel drug delivery system using nanoscale materials with a broad spectrum of applications provides a new therapeutic foundation for technological integration and innovation. Nanoparticles are suitable drug carrier for various routes of administration as well as rapid recognition by the immune system. Gelatin, the biological macromolecule is a versatile drug/vaccine delivery carrier in pharmaceutical field due to its biodegradable, biocompatible, non-antigenicity and low cost with easy availability. The surface of gelatin nanoparticles can be modified with site-specific ligands, cationized with amine derivatives or, coated with polyethyl glycols to achieve targeted and sustained release drug delivery. Compared to other colloidal carriers, gelatin nanoparticles are better stable in biological fluids to provide the desired controlled and sustained release of entrapped drug molecules. The current review highlights the different formulation aspects of gelatin nanoparticles which affect the particle characteristics like zeta potential, polydispersity index, entrapment efficacy and drug release properties. It has also given emphasis on the major applications of gelatin nanoparticles in drug and vaccine delivery, gene delivery to target tissues and nutraceutical delivery for improving the poor bioavailabity of bioactive phytonutrients.

Introduction

Nanoscience is a subject of substantial curiosity which associated with special properties of nanoparticles like surface to volume ratio, surface reactivity and their porous or core shell structure [1]. Compared to other carrier systems, nanoparticles have better accumulation, especially macrophage rich organs, e.g., lungs, liver, and spleen because of their preferential phagocytosed [2]. Biodegradable nanoparticles have been used frequently as drug delivery vehicles due to their outstanding bioavailability, better encapsulation, controlled and targeted release as well as less toxic properties [3]. Gelatin based nanoparticles (GNPs) are promising carrier for drug conveyance due to the harmless, biocompatible, recyclable, non-antigenicity, prudential, abundant renewable sources, extra ordinary binding capacity of various active groups for attaching targeting molecules and possibility of less opsonization by the reticuloendothelial system (REs) through an aqueous steric barrier in addition to greater stability during storage and in vivo [4]. Moreover, researchers have major focus on gelatin polymer due to its high content of amino acids like glycine, proline and alanine which occur in repeating sequences and confer on gelatin as triple helical structure [5], [6].

Gelatin, the denatured protein is obtained either by partial acid or alkaline hydrolysis or by thermal or enzymatic degradation of structural animal collagen protein. Collagen signifies 30% of all vertebrate body proteins. More than 90% of the extra cellular protein in the tendon & bone and more than 50% protein in the skin consist of collagen [7]. Commercially two different types of gelatin (type A & type B) are available depending on the method of collagen hydrolysis. Gelatin A is obtained from porcine skin with acid pre-treatment prior to the extraction process which scarcely affects the amide groups of glutamine and asparagine results a higher isoelectric point IEP (i.e.,7–9) [8]. On the other hand gelatin B is extracted from ossein and cut hide split from bovine with alkaline treatment causes hydrolyses of asparagine and glutamine to aspartate and glutamate respectively. Thus, type B gelatin possesses a greater proportion of carboxyl groups showing negatively charge and lowering IEP (i.e., 4.5–6.0) [9].

The long history of safe use in pharmaceuticals, cosmetics, as well as food products, gelatin is considered as GRAS (generally regarded as safe) material by the United States Food and Drug Administration (US FDA) [10]. Gelatin is used clinically as a plasma expander and stabilizer in a number of protein formulations, vaccines and gelatin sponges. Gelatin cannot produce any harmful by-products upon enzymatic degradation as it is derived from collagen, the most abundant protein in animals. Its chains are designed as Arg-Gly-Asp (RGD) sequences which modify cell adhesion, improve the biological behaviour and the cell recognition sites [11]. Gelatin has intrinsic protein structure with large number of different accessible functional groups, multiple modification opportunities for coupling with cross-linkers and targeting ligands which may be especially useful for developing targeted drug delivery vehicles [12]. In addition, gelatin as a matrix for mineralization has evoked a lot of interest in the field of tissue engineering [13].

Section snippets

Chemistry of gelatin

Gelatin is a natural, biodegradable protein obtained by acid- or base-catalyzed hydrolysis of collagen. It is a polyampholyte macromolecule having both cationic and anionic along with hydrophobic groups [14]. Gelatin molecules contain repeating sequences of glycine, proline and alanine amino acid triplets, which are responsible for the triple helical structure of gelatin. The triple helical structure of gelatin is represented as (Gly-X-Pro)n, where X represented as the amino acid, mostly

Methods for preparation of GNPs

The properties of GNPs can be optimized depending on the particular application. In order to achieve the properties concern, the methods of preparation performance are a vital role. Thus, it is highly expedient of the preparation techniques to obtain GNPs with desired properties for a particular application. The following methods have been employed to prepare GNPs.

Particle size

The size of the nanoparticles has a great impact on its uptake. The small nanoparticles have large surface area, more absorption and more bioavailability. Desai and co-workers showed that 100 nm size nanoparticles have 2.5 fold greater uptakes compared to 1 μm and 6 fold higher uptakes compared to 10 μm sized particles in a Caco-2 cell line [54]. Drug or vaccine loading efficiency and sustained release kinetics are mainly depends upon size of the nanoparticles. Smaller particles have a larger

Surface modified GNPs

One of the problems for use of nanoparticles via the intravenous route is their speedy removal by the phagocytic cells (macrophages) in the body [55]. Macrophages are powerful phagocytic cells of mononuclear phagocytic system (MPs) which is one of the body's innate defence systems. When any particulate matter including GNPs are injected into the blood stream, it is recognized as foreign body by MPs, then they are phagocytised and removed from the circulation. Hence, there should be a

Anti-cancer drug delivery

The rationale of using nanoparticles for tumour targeting is based on (1) the ability to deliver the requisite dose of drug in the vicinity of the tumour due to the enhanced permeability and retention effect (EPR effect) or active targeting by ligands on the surface of nanoparticles and (2) the ability to reduce the drug exposure to healthy tissues by limiting drug distribution to the target organ [55]. GNPs have been extensively used for the targeted delivery and controlled release of

Drawbacks and challenges

Significant applications of GNPs as drug/vaccine delivery vehicle in various fields have been developed. However, there is a still critical problem associated with the use of animal origin gelatin which carries the risk of contamination with transmissible spongiform encephalopathy (TSE). The rigorous manufacturing processes such as acid, alkaline and heat treatments are employed to inactivate TSE agents and minimize TSE risk in drug products [49], [62], [146]. Currently, there are commercial

Conclusion

Biodegradable GNPs can be a promising drug delivery carrier system for its versatile formulation, controlled and sustained release properties, sub-cellular size and biocompatible with various cells and tissues in the body is well established. Surface modification of GNPs achieved long-time circulation and site specific drug action in the body. Although many important goals have been reached to achieve the stability of drugs in circulation, yet more investigations need to be developed with

Acknowledgment

This study has financed by All India Council for Technical Education, Department of Higher Education, Ministry of Human Resource Development, New Delhi, India.

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