Abstract
Objective: This study aimed to characterize the physicochemical properties, including pH, zeta potential, and particle size of propranolol-loaded nanoparticles that were incorporated into a buccal transmucosal drug-delivery system.
 Methods: An ionotropic gelation technique was used to formulate propranolol-loaded chitosan nanoparticles. Chitosan used as the nanoparticle base, using tripolyphosphate (TPP) as a cross-linking agent. The effects on nanoparticle physical properties, including pH, zeta potential, and particle size were examined when various chitosan [0.150-0.300 % (w/v)] and propranolol contents (0-40 mg) were used during the preparation. The effects of using chitosan solutions with different pH values on nanoparticle properties were also determined.
 Results: The pH values of all nanoparticles ranged between 4.14–4.55. The zeta potentials of the prepared nanoparticles ranged between 22.6–52.6 mV, with positive charges. The nanoparticle sizes ranged from 107–140 nm, which are within the range of suitable particle sizes for transmucosal preparations.
 Conclusion: The pH values, zeta potentials, and particle sizes of the nanoparticle formulations were influenced by the concentrations of chitosan and propranolol and by the pH of the initial chitosan solution. The relationships between nanoparticle properties and all factors primarily depended on the ionic charges of the components, especially chitosan. Our study provides beneficial physicochemical knowledge for the further development of chitosan-based nanoparticles containing propranolol for buccal drug delivery systems.
Highlights
Nanoparticles have been researched considerably in pharmaceutical fields for their potential to carry drugs or active substances directly to target sites, due to their intrinsic properties to control drug release, to protect drugs from hazardous environments, and to increase drug absorption and permeation through mucosal membranes [1, 2]
Ionotropic gelation is one of the most common techniques for the generation of nanoparticles used for drug incorporation, which involves an ionic interaction between the positive charges of chitosan and the negative charges of polyanion molecules, such as tripolyphosphate (TPP) [14, 15]
The nanoparticle formulations were composed of chitosan at seven concentrations [0.150–0.300 % (w/v)] and five levels of propranolol (0, 10, 20, 30, and 40 mg)
Summary
Nanoparticles have been researched considerably in pharmaceutical fields for their potential to carry drugs or active substances directly to target sites, due to their intrinsic properties to control drug release, to protect drugs from hazardous environments, and to increase drug absorption and permeation through mucosal membranes [1, 2]. Various natural polymers have been used to improve the cell permeation of buccal drug delivery, including chitosan, alginate, agarose, and gums [7]. Chitosan facilitates the penetration of drugs, using both transcellular and paracellular transportation through the mucus membrane [4, 9, 10]. The positive charges on chitosan interact with negatively charged mucus components, resulting in the reorganization of the tight junction, which opens the epithelial junction [10, 11]. Ionotropic gelation is one of the most common techniques for the generation of nanoparticles used for drug incorporation, which involves an ionic interaction between the positive charges of chitosan and the negative charges of polyanion molecules, such as tripolyphosphate (TPP) [14, 15]. Ionotropic gelation is a simple technique and has many advantages, such as mild conditions, preparation in aqueous environments, and low toxicity [4]
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