Recent Progress of Chitosan and Chitosan Derivatives-Based Nanoparticles: Pharmaceutical Perspectives of Oral Insulin Delivery

Abstract

Diabetes mellitus is a chronic endocrine disease, affecting more than 400 million people around the world. Patients with poorly controlled blood glucose levels are liable to suffer from life-threatening complications, such as cardiovascular, neuropathy, retinopathy and even premature death. Today, subcutaneous parenteral is still the most common route for insulin therapy. Oral insulin administration is favourable and convenient to the patients. In contrast to injection route, oral insulin delivery mimics the physiological pathway of endogenous insulin secretion. However, oral insulin has poor bioavailability (less than 2%) due to the harsh physiological environment through the gastrointestinal tract (GIT). Over the last few decades, many attempts have been made to achieve an effective oral insulin formulation with high bioavailability using insulin encapsulation into nanoparticles as advanced technology. Various natural polymers have been employed to fabricate nanoparticles as a delivery vehicle for insulin oral administration. Chitosan, a natural polymer, is extensively studied due to the attractive properties, such as biodegradability, biocompatibility, bioactivity, nontoxicity and polycationic nature. Numerous studies were conducted to evaluate chitosan and chitosan derivatives-based nanoparticles capabilities for oral insulin delivery. This review highlights strategies that have been applied in the recent five years to fabricate chitosan/chitosan derivatives-based nanoparticles for oral insulin delivery. A summary of the barriers hurdle insulin absorption rendering its low bioavailability such as physical, chemical and enzymatic barriers are highlighted with an emphasis on the most common methods of chitosan nanoparticles preparation. Nanocarriers are able to improve the absorption of insulin through GIT, deliver insulin to the blood circulation and lower blood glucose levels. In spite of some drawbacks encountered in this technology, chitosan and chitosan derivatives-based nanoparticles are greatly promising entities for oral insulin delivery.

Antimicrobial Actions and Applications of Chitosan

“…Chitosan nanoparticles are synthesized for different purposes by various methods, such as ionotropic gelation, polyelectrolyte complexation, emulsification solvent diffusion, microemulsion, and reverse micelle formation [ 204 , 205 ]. Moreover, the antimicrobial effects of chitosan-based nanoparticles for drug and drug-free delivery systems have been intensively investigated against bacteria and fungi [ 56 , 57 , 58 , 60 , 63 , 67 , 68 , 106 , 119 , 203 , 206 , 207 , 208 , 209 , 210 , 211 , 212 ].…”

Evaluation of Antinociceptive Effects of Chitosan-Coated Liposomes Entrapping the Selective Kappa Opioid Receptor Agonist U50,488 in Mice

“…For obtaining chitosan-based nanoparticles, several methods have been described: polyelectrolyte complexation, emulsion-droplet coalescence, emulsion crosslinking, ionotropic gelation, reverse micellization, and precipitation [ 48 , 51 ].…”

Advances in Chitosan-Based Nanoparticles for Drug Delivery

“…The organic solvent is evaporated and the created NPs can be harvested by precipitation with a suitable salt. The solution is then centrifuged, and the aqueous supernatant is dialyzed for about 1 h and lyophilized to dry powder [9,88].…”

“…The advantages of this method are associated with the ability to produce a small particle size with a narrow size of the distribution. On the other hand, the disadvantages include the laborious and time-consuming process and the presence of organic solvent and surfactant [88].…”

“…In the case of hydrophilic drugs, a multiple water/oil/water emulsion (e.g., double emulsion) needs to be formed with the drug dissolved in the internal aqueous phase. The major drawbacks of this method include harsh processing conditions (e.g., the use of organic solvents) and the high shear forces used during NP preparation [70,87,88]. Often, this method is used for the preparation of PLGA NPs with CS as a coating material.…”