Alginate nanoparticles as ocular drug delivery carriers

Abstract

The eye is the most susceptible organ of the body by assigning 30% of the brain cells and is exposed to various environmental damage due to contact with the outside environment. In addition, multiple internal factors such as genetics, aging, and diabetes are associated with damage to the various regions of this organ. Due to the high sensitivity of this organ, the body has provided many protective systems that end with a limited supply of drugs to this tissue. The most common form of drug delivery to ocular tissue is the use of eye drops. Due to the presence of these protective systems, less than 5% of the drug reaches the targeted tissue. This raises the importance of designing a drug delivery system that remains at the surface of the eye while controlling drug release, increases the bioavailability of the drug, and reduces the need for frequent drug administration. In this study, alginate nanoparticles were prepared to fulfill this purpose for the delivery of betamethasone sodium phosphate, an anti-inflammatory drug. For the preparation of alginate nanoparticles, three methods of electrospraying, emulsification, and a combination of these two methods were used, among which emulsification was selected as the preferred method. In the next step, to improve the adhesion properties and control of drug release, coating of the alginate nanoparticles was carried out using two cationic polymers of chitosan and gelatin. Scanning electron microscopy images represented the spherical morphology of alginate nanoparticles, the dimension of which was between 130 and 150 nm in blank alginate-based nanoparticles. By drug encapsulation, the dimension increases between 150 and 300 nm. Furthermore, the Zeta potential test indicated that the charge of the alginate nanoparticles was negative at about −18 mV. The changes in the zeta potential of gelatin and chitosan-coated nanoparticles, besides differential scanning calorimetry obtained thermograms, confirmed the formation of coating layers on the surface of the nanoparticles. The mucoadhesion analysis showed the highest mucoadhesive strength of about 75% in gelatin-coated alginate nanoparticles. The encapsulation efficiency and loading capacity of the alginate nanoparticles were about 40 and 7%, respectively. Finally, results obtained by in vitro drug release assay demonstrated sustained drug release in a period of 120h, the mechanism of which followed the Korsmeyer-Peppas model. In both uncoated and coated samples, the need for duplicate treatment was less than the commercial drop of the drug that paves the path for improving the quality of life of patients suffer from eye diseases.