Zinc and Calcium Cations Combination in the Production of Floating Alginate Beads as Prednisolone Delivery Systems

Abstract

The aim of this research was to verify the application of alginate in combination with Ca2+ and Zn2+ ions to produce a floating and prolonged release system for the oral administration of prednisolone. Hollow and floating gel-beads were designed using prilling/ionotropic gelation as the microencapsulation technique, zinc acetate in the gelling solution as the alginate external crosslinker, and calcium carbonate in the feed as the internal crosslinking agent able to generate gas when in contact with the acidic zinc acetate solution. To achieve this goal, drug/alginate solutions were opportunely combined with different amounts of calcium carbonate. The effect of the addition of calcium carbonate into the feed solution on buoyancy, encapsulation efficiency, morphology, size distribution, as well as in vitro drug release profile of the alginate particles was studied. Moreover, the ability of the floating beads to modulate in vivo the anti-inflammatory response was assayed using the carrageenan-induced acute oedema in rat paw. The proposed strategy allowed obtaining alginate beads with extremely high encapsulation efficiency values (up to 94%) and a very porous inner matrix conferring buoyancy in vitro in simulated gastric fluid up to 5 h. Moreover, in vivo, the best formulation, F4, resulted in the ability to prolong the anti-inflammatory effect up to 15 h compared with raw prednisolone.

Studies on Encapsulation of Gas Releasing Agent in Ca-Alginate Beads and Controlled Release Pattern of the Beads

“…Ca-alginate beads has been getting much attention in recent years. For example, carbon dioxide gas generating agents such as carbonate and bicarbonate salt, which can generate CO2 under acidic conditions to produce low-density floating drug delivery carriers (Choi et al, 2002;Magdhut et al, 2023;Rasel et al, 2012;Russo et al, 2020).…”

“…The release of gas or vapor from the encapsulated gas releasing agent or volatile compounds in Ca-alginate beads can be initiated by introducing an acidic or alkaline solution, moisture, or heat to decompose the encapsulated materials (Cha et al, 2021;Lee et al, 2014;Magdhut et al, 2023;Paris et al, 2020;Petzold et al, 2014;Rasel et al, 2012;Russo et al, 2020) beads was measured using a CO2 gas sensor, and the gas release pattern was reported.…”

Natural Polymers in Micro- and Nanoencapsulation for Therapeutic and Diagnostic Applications: Part I: Lipids and Fabrication Techniques

“…Most used shell materials are lipids, waxes, fats and gelling hydrocolloids. Russo and colleagues [30] recently explored the possibility of combining Zn and Ca cations as an ionic gelation agents for prednisolone encapsulated alginate beads developed with the Prilling technique. The calcium carbonate decomposed internally in the acidic environment releasing a gas that increased porosity of the microcapsules ultimately translating to buoyancy in the gastrointestinal fluid and extended hours of anti-inflammatory effect.…”

Technologies and Formulation Design of Polysaccharide-Based Hydrogels for Drug Delivery

“…In the most of them, calcium has been used as external cross-linker for the gelation phase [157,211,212]. More recently, an important milestone was achieved with the simultaneous use of two different divalent cations to produce floating and prolonged release alginate PbHPs for the oral administration of prednisolone, P [207]. Critical parameters were established: prilling/ionotropic gelation was used as microencapsulation technique, zinc acetate in the gelling solution as the alginate external crosslinker, and calcium carbonate in the feed acting as the internal crosslinking agent able to generate gas when in contact with the acidic zinc acetate solution.…”