PREPARATION AND CHARACTERIZATION OF LOW MOLECULAR WEIGHT CHITOSAN WITH DIFFERENT DEGREES OF DEACETYLATION BY THE ACID HYDROLYSIS METHOD

Objective: The objective of this research is to prepare Low Molecular Weight Chitosan (LMWC) by the acid hydrolysis method, using dilute hydrochloric acid (2M). LMWC has superior properties compared to the High Molecular Weight Chitosan (HMWC), especially in terms of water solubility, antibacterial and antifungal properties. These could open new potential applications for LMWC in sectors such as the cosmetics, food, and pharmaceutical industries. Methods: In this work, the acid hydrolysis method was used to produce LMWC with different molecular weights starting from 500 kDa and 93% degree of deacetylations (DDA). The molecular weights of the produced grades were determined by applying Mark-Houwink equation while the %DDA was determined and verified by the use of the 1st derivative UV method and 1HNMR method, respectively. The depolymerization reactions were carried out with different time intervals to produce totally deacetylated LMWC of 30 kDa, 15 kDa, and 7.5 kDa. The LMWC was characterized by FTIR, XRD, and DSC to evaluate the functionality, microstructure and thermal properties. Results: The FTIR spectra revealed that there is no significant difference in the main skeletal structure of the LMWC and HMWC. On the other hand, the XRD and DSC results showed that the LMWC of different molecular weights and degrees of deacetylation are of semi-crystalline structure, similar to the HMWC. Conclusion: The obtained results showed that the used acid hydrolysis procedure can produce LMWC grades of desired specifications, yields, and quality which are suitable for use in different applications

Influence of Molecular Weight and Degree of Deacetylation of Low Molecular Weight Chitosan on the Bioactivity of Oral Insulin Preparations

The objective of the present study was to prepare and characterize low molecular weight chitosan (LMWC) with different molecular weight and degrees of deacetylation (DDA) and to optimize their use in oral insulin nano delivery systems. Water in oil nanosized systems containing LMWC-insulin polyelectrolyte complexes were constructed and their ability to reduce blood glucose was assessed in vivo on diabetic rats. Upon acid depolymerization and testing by viscosity method, three molecular weights of LMWC namely, 1.3, 13 and 18 kDa were obtained. As for the DDA, three LMWCs of 55%, 80% and 100% DDA were prepared and characterized by spectroscopic methods for each molecular weight. The obtained LMWCs showed different morphological and in silico patterns. Following complexation of LMWCs with insulin, different aggregation sizes were obtained. Moreover, the in vivo tested formulations showed different activities of blood glucose reduction. The highest glucose reduction was achieved with 1.3 kDa LMWC of 55% DDA. The current study emphasizes the importance of optimizing the molecular weight along with the DDA of the incorporated LMWC in oral insulin delivery preparations in order to ensure the highest performance of such delivery systems

Further investigation on the degree of deacetylation of chitosan determined by potentiometric titration

The degree of deacetylation (DDA) of various low molecular weight chitosan (LMWC) species as the hydrochloride and free base (amine form) was determined by direct and back potentiometric titration, respectively. The DDA values obtained for the chitosan hydrochloride by direct titration were greater than 93% for all oligomers tested (Molecular weight (Mwt) between about 1.3 to 30.0 kDa). However, the DDA values obtained for chitosan amine oligomers using back titration were significantly lower, especially for the relatively high molecular weight (30.0 kDa) chitosan amine oligomers. Furthermore, after using the back titration method, greater DDA values were obtained for the same samples of chitosan amine after the chitosan solution had been heated to 60EC before titration. In addition, the DDA values showed a significant decrease with increased concentration for a given chitosan oligomer. Although the effects of hydration time, ionic strength and method specific behavior were not explicitly studied and therefore cannot be entirely ruled out, the results from this study might be attributed to the conformation of changes of chitosan in solution that lead to more inter/intra attractive forces in the case of chitosan amine. The DDA values obtained by the potentiometric method were also compared with those obtained by the FDUV and IR spectroscopic methods. Thus, subject to the caveats mentioned above, DDA values obtained for chitosan amine by the back titration method should be used with caution since the results are significantly lower than those obtained by direct titration, FDUV spectroscopy or FTIR

Preparation and characterization of low molecular weight chitosan with different degrees of deacetylation by the acid hydrolysis method

Objective: The objective of this research is to prepare Low Molecular Weight Chitosan (LMWC) by the acid hydrolysis method, using dilute hydrochloric acid (2M). LMWC has superior properties compared to the High Molecular Weight Chitosan (HMWC), especially in terms of water solubility, antibacterial and antifungal properties. These could open new potential applications for LMWC in sectors such as the cosmetics, food, and pharmaceutical industries. Methods: In this work, the acid hydrolysis method was used to produce LMWC with different molecular weights starting from 500 kDa and 93% degree of deacetylations (DDA). The molecular weights of the produced grades were determined by applying Mark-Houwink equation while the %DDA was determined and verified by the use of the 1st derivative UV method and1HNMR method, respectively. The depolymerization reactions were carried out with different time intervals to produce totally deacetylated LMWC of 30 kDa, 15 kDa, and 7.5 kDa. The LMWC was characterized by FTIR, XRD, and DSC to evaluate the functionality, microstructure and thermal properties. Results: The FTIR spectra revealed that there is no significant difference in the main skeletal structure of the LMWC and HMWC. On the other hand, the XRD and DSC results showed that the LMWC of different molecular weights and degrees of deacetylation are of semi-crystalline structure, similar to the HMWC. Conclusion: The obtained results showed that the used acid hydrolysis procedure can produce LMWC grades of desired specifications, yields, and quality which are suitable for use in different applications

Further investigation on the degree of deacetylation of chitosan determined by potentiometric titration

The degree of deacatylation (DDA) of various low molecular weight chitosan (LMWC) species in the hydrochloride and amine forms was determined by direct and back potentiometric titration, respectively. It has been found that the DDA values obtained for the chitosan hydrochloride oligomers by the direct titration are better than 93% for all oligomers (Mwt of about 1.3 to 30.0 kDa) studied. However those DDA values obtained by the back titration of chitosan amine oligomers were significantly low especially for the relatively high molecular weight (30.0 kDa) chitosan amine oligomers. Furthermore, DDA values of chitosan amine have been increased when the chitosan solution was heated up to 60oC before titration. Also, the %DDA values showed a significant decrease with the concentration of the same chitosan oligomer. All these behaviors might be attributed to the conformation changes of chitosan in solution that lead to more inter/intra attractive forces in the case of chitosan amine. Thus, there is a concern about the DDA values obtained for chitosan amine by the back titration method since the results are always significantly lower than anticipated. The DDA values obtained by the potentiometric method were also compared with those obtained by the UV and IR spectroscopic methods

Factors involved in formulation of oily delivery system for proteins based on PEG-8 caprylic/capric glycerides and polyglyceryl-6 dioleate in a mixture of oleic acid with Chitosan

Systematic experimental work is required to improve knowledge related to the use of oily delivery systems. This work aimed to examine the influence of different molecular weights chitosan on formation and solubilization ability of w/o system of Labrasol, Plurol Oleique, water and oleic acid. Phase diagrams were constructed. Size measurements were performed for each surfactant in oleic acid. Interfacial tension of chitosan was measured between oleic acid and water at pH 1.5 and 6.25. Effect of chitosan on microemulsion size was studied. When used to deliver rh insulin to diabetic rats, the mixture showed reduction in blood glucose compared to control

An Overview of Chitosan Nanofibers and their Applications in the Drug Delivery Process

Chitosan is a polycationic natural polymer which is abundant in nature. Chitosan has gained much attention as natural polymer in the biomedical field. The up to date drug delivery as well as the nanotechnology in controlled release of drugs from chitosan nanofibers are focused in this review. Electrospinning is one of the most established and widely used techniques for preparing nanofibers. This method is versatile and efficient for the production of continuous nanofibers. The chitosan-based nanofibers are emerging materials in the arena of biomaterials. Recent studies revealed that various drugs such as antibiotics, chemotherapeutic agents, proteins and anti-inflammatory analgesic drugs were successfully loaded onto electrospun nanofibers. Chitosan nanofibers have several outstanding properties for different significant pharmaceutical applications such as wound dressing, tissue engineering, enzyme immobilization, and drug delivery systems. This review highlights different issues of chitosan nanofibers in drug delivery applications, starting from the preparation of chitosan nanofibers, followed by giving an idea about the biocompatibility and degradation of chitosan nanofibers, then describing how to load the drug into the nanofibers. Finally, the major applications of chitosan nanofibers in drug delivery systems