Pectin and Zinc Alginate: The Right Inner/Outer Polymer Combination for Core-Shell Drug Delivery Systems

Abstract

Core-shell beads loaded with betamethasone were developed using co-axial prilling as production technique and pectin plus alginate as polymeric carriers. During this study, many operative conditions were intensively investigated to find the best ones necessary to produce uniform core-shell particle systems in a reproducible way. Particularly, feed solutions’ composition, polymers mass ratios and the effect of the main process parameters on particles production, micromeritics, inner structure, drug loading and drug-release/swelling profiles in simulated biological fluids were studied. The optimized core-shell formulation F5 produced with a pectin core concentration of 4.0% w/v and an alginate shell concentration of 2.0% w/v (2:1 core:shell ratio) acted as a sustained drug delivery system. It was able to reduce the early release of the drug in the upper part of the gastro-intestinal tract for the presence of the zinc-alginate gastro-resistant outer layer and to specifically deliver it in the colon, thanks to the selectivity of amidated low methoxy pectin core for this district. Therefore, these particles may be proposed as colon targeted drug delivery systems useful for inflammatory bowel disease (IBD) therapy.

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

“…Prilling is a mild and scalable microencapsulation technique working essentially through two steps: the breaking apart of a laminar jet of alginate solution into a row of mono-sized drops through a vibrating nozzle and the successive drops' ionotropic gelling in a solution of cations acting as crosslinkers. In the last few years, a large variety of gel-beads has been produced, varying the types of polysaccharides (mainly alginate, pectin, chitosan, and so on) used alone or in combination [10,11]; the configuration of the prilling apparatus to obtain 'only core' or core-shell beads [12]; and the gelling conditions in terms of cross-linker, pH of the reticulation solution, and gelling time [13,14]. Moreover, calcium alginate has often been used in combination with different gas-generating agents such as sodium bicarbonate, calcium carbonate, and citric acid or tartaric acid to obtain low-density floating formulations [15][16][17].…”

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

“…The technology has been shown especially suitable to immobilize microorganisms or entrap bioactive substances in polymeric beads; these are formed by fall of a mixed host-polymer liquid formulation into an appropriate polymer gelling solution [25][26][27][28]. Recently, many pharmaceutical applications of such beads have been developed in order to control the drug release in orally administered formulations [29,30] or the colon targeting [31,32].…”

“…The appropriate combination of two or more polysaccharides may be, for example, an effective way to produce a polymer-drug core (e.g., pectin) enveloped by gastroresistant shell (e.g., alginate) able to prevent the early release of the drug in the upper part of the gastro-intestinal tract (GIT) [45][46][47][48]. An enteric shell may release the drug in a specific district of the organism (intestinal/colonic tract); moreover, from the use of bioadhesive polymers may increase the gastric retention time and, therefore, improve the localized action in GI tract or even delay the release in a precise moment of the day as required, for example, for the treatment of severe chronic mucosal inflammations such as Inflammatory bowel disease IBD [31]. Viscosity is certainly one of the most important variable of this technique; prilling is able to process only solutions with viscosity values lower than few hundreds of mPa•s [21] and it is essential to study the so-called nozzle viscosity (dynamic viscosity) using appropriate theoretical model [23].…”

“…In general, to increase the performances of such particle systems and make more efficient the delivery of macromolecules as well as drugs throughout the GIT, the manufacturing phase should provide a major control on shell formation process. To this regard, an important achievement was the design and the development of multiparticulate beads in core-shell configuration using (a) prilling apparatus in its basic configuration followed by an enteric coating process [32,205] and (b) prilling apparatus in coaxial configuration [31,43]. This latter is certainly the most innovative approach; it employs multiple concentric nozzles to produce a smooth coaxial jet comprising polymer annular shell and core material, which are broken up by acoustic excitation into uniform core-shell droplets and gelled into a cross-linking solution.…”

Combining valproate and bipyridyl ligands to construct a 0D core-shell Zn5(μ3-OH)2 cluster and a 2D layered coordination network with a [Zn3(μ3-OH)]2 SBU

“…These molecular building blocks can serve as secondary building units (SBUs) to construct extended networks like 2D coordination networks with structural novelty and possible interesting properties (Li et al, 2018;Ha et al, 2018). In particular, recent examples of zinc coordination networks showed promising applications that include drug delivery (Liu et al, 2019;Auriemma et al, 2020), gas storage (Lo et al, 2016), sensing (Zhang et al, 2018) and luminescence properties (Panunzi et al, 2018;Diana et al, 2019).…”