Amir Abbas Samani 1, Javad Yazdani 2, Azin Jahangiri 3,*
1 William Osler Health Center, Brampton, Canada
2 Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Department of Pharmaceutics, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
*Correspondence: Azin Jahangiri, Department of Pharmaceutics, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran, Phone: +984432754991, Urmia, Iran. Email: : jahangiri.az@umsu.ac.ir
Abstract
It seems that an ever-increasing tendency is necessary to develop a methodology that can not only protect the proteins and peptides from enzymatic degradation but also can help in improving their absorption without changing their biological activity. Oral delivery of proteins and peptides seems an attractive option, however, for its availability, some distinctive challenges should be met. A wide range of different carriers has been reported for use in the delivery of proteins and peptides to protect their formulation and structure against the acidic medium and enzymatic environment of the GI tract. Hydrogels, as the networks of polymeric systems, have been extensively examined as the drug delivery structures. This review emphasizes protein/peptide drug delivery using hydrogel systems.
Keywords: Oral delivery, Protein, Peptide, Hydrogel
Introduction
The main and powerful role of the proteins/peptides converts them as drug choices for the dealing of several diseases. Main problems in protein delivery are the maintenance of proteins in delivery systems and the preparation of suitable target-specific protein transporters. Many studies have been performed to the efficient delivery of proteins/peptides over different routes of administrations for an effective therapeutic action [1-3]. Modification of the surface of proteins and peptides by polyethylene glycol (PEG), known as PEGylating, can increase the circulating life, solubility and
stability, pharmacokinetic possessions, and antigenicity of them. Biodegradable polymeric nanoparticulate systems such as polylactic acid (PLA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), as well as solid lipids, liposomes, niosomes, aquasomes and, hydrogels have exposed excessive potential in the delivery of proteins/peptides [4-9]. Hydrogels, as the swellable structures, have been extensively examined as the drug delivery areas. They have revealed good attention due to the outstanding properties like swelling in the aqueous medium, pH and temperature sensitivity or sensitivity to other stimuli. They are also known as biocompatible materials that function as drug protectors from an in vivo environment. They have also abilities to act as carriers with targeting ability for drugs with tissue specificity [10,11]. This review focuses on effective protein/peptide drug delivery using hydrogel systems.
Hydrogels
Hydrogels are 3D-dimensional polymeric structures having hydrophilic segments that absorb huge quantities of water and form a gel-like system. The formed network resulted from the cross-linking of polymer chains. Recently, artificial hydrogels offer an effective and appropriate system to administer peptides and proteins [3,5]. These systems exist in two types of neutral hydrogels, and ionic hydrogels. The hydrogels made from natural polymers are neutral hydrogels that are mainly biocompatible and biodegradable [10,11]. But, they do not possess suitable mechanical strength and also may include pathogens that may cause an auto-immune response. Ionic hydrogels include classes that ionize in response to variation in environments, creation the hydrogel system swelling. Hydrogels with ability to respond to the presence of different stimuli (such as temperature, ionic strength variation and, pH alteration) are recognized as physiologically-responsive hydrogels [2,3].
Two different classes of hydrogels have been introduced in the literature; performed and in-situ forming hydrogels. While in situ forming gels show gelation process in the administration procedure, performed hydrogels do not have any changes after administration as they are simple viscous solutions. The polymeric network of hydrogels can be either homopolymers or copolymers. The chief broadly used polymers in designing of hydrogels for protein delivery are 2-hydroxyethyl methacrylate, ethylene glycol dimethacrylate, N-isopropyl acrylamide, acrylic acid and methacrylic acid [1-3, 10,11].
Oral delivery of proteins and peptides by hydrogel systems
Hydrogels have been synthesized and used as the drug reservoir matrix for peptide/protein-based pharmaceuticals in some recent studies.
In a work by Ichikawa et al., a hydrogel-based on poly [methacrylic acid-grafted-poly (ethylene glycol)] [P(MAA-g-EG)] were designed for insulin delivery by the oral way. They studied cytotoxicity and insulin-transport improving outcomes of P(MAA-g-EG) hydrogels on intestinal epithelial cells. The obtained outcomes showed that the P(MAA-g-EG) hydrogels were cytocompatible and have a transport-enhancing influence of insulin on intestinal epithelial cells [12].
Recently, in a study by Kamei et al. P(MAA-g-EG) complex hydrogels have reported showing high encapsulation percent and incorporation efficiency for insulin, calcitonin and interferon β. Besides, calcitonin and interferon β loaded systems showed complexation/decomplexation and pH-sensitive release pattern while fast insulin release in the intestine with a pH-controlled performance. The in vivo results also showed a dose-dependent increase of plasma interferon β levels and a severe decrease in plasma calcium levels convoyed with calcium absorption detected after administration of interferon β or calcitonin into closed rat ileal sections. These results suggest P(MAA-g-EG) hydrogels as effective transporters for the delivery of peptides and proteins by oral route [13].
Peppas et al. tested the swelling behaviour and solute release possessions of hydrogel systems organized by bulk polymerization to create the association between complexation, swelling and solute release. According to the authors, these systems can be beneficial in controlled release options owing to their large, manageable swelling transitions. The hydrogels were swollen in water with a pH of 1.5-12.0. They tested solute release to examine the influence of pH and swelling on the release performance. Complex-forming networks observed for lowest solute release rates in confirming the association between complexation, swelling and solute penetrability [10].
Bajpai et al. synthesized a hydrogel system by the copolymerization of acrylamide and itaconic acid using poly(N-vinyl-2-pyrrolidone). Their reports showed that a small amount of itaconic acid caused the transition of the swelling manner. The prepared hydrogels presented a good reaction to the valency of the counterions and pH of swelling media. The hydrogels presented low- temperature dependence. The hydrogels showed a potential role as transporters for oral delivery of peptides and proteins [11].
Conclusion and future direction
The field of oral delivery for proteins and peptides seems an attractive option, however, for its availability, some distinctive challenges should be met. Wide ranges of different carriers have been reported for use in delivery of proteins and peptides to protect their formulation and structure against the acidic medium and enzymatic environment of the GI tract. This paper emphasized on oral protein/peptide drug delivery using hydrogel systems. The investigated texts showed the beneficial effects of hydrogels as delivery systems for protein and peptides. For future studies, it should be considered that artificial hydrogels do not display the basic bioactive possessions and can be used to produce hydrogels with favorite degradability and functionality. One significant option to be considered is the space between cross-links in the hydrogel matrix. Any alteration in the cross-links may alter the diffusion outline of a drug from the hydrogel system.
Conflict of interests
The authors state that there are no conflicts of interest in this paper.
References
HOW TO CITE
Samani, A. A., Yazdani, J., & Jahangiri, A. (2019). Oral delivery of proteins and peptides by hydrogel systems: a brief overview. Journal of Advanced Chemical and Pharmaceutical Materials (JACPM), 2(1), 100-102. Retrieved from http://advchempharm.ir/journal/index.php/JACPM/article/view/65
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