Ionic Cross-Linking as a Strategy to Modulate the Properties of Oral Mucoadhesive Microparticles Based on Polysaccharide Blends

Abstract

Polymer blends of gellan gum (GG)/retrograded starch(RS) and GG/pectin (P) were cross-linked with calcium, aluminum, or both to prepare mucoadhesive microparticles as oral carriers of drugs or nano systems. Cross-linking with different cations promoted different effects on each blend, which can potentially be explored as novel strategies for modulating physical–chemical and mucoadhesive properties of microparticles. Particles exhibited spherical shapes, diameters from 888 to 1764 µm, and span index values lower than 0.5. Blends of GG:P cross-linked with aluminum resulted in smaller particles than those obtained by calcium cross-linking. GG:RS particles exhibited larger sizes, but cross-linking this blend with calcium promoted diameter reduction. The uptake rates of acid medium were lower than phosphate buffer (pH 6.8), especially GG:RS based particles cross-linked with calcium. On the other hand, particles based on GG:P cross-linked with calcium absorbed the highest volume of acid medium. The percentage of systems erosion was higher in acid medium, but apparently occurred in the outermost layer of the particle. In pH 6.8, erosion was lower, but caused expressive swelling of the matrixes. Calcium cross-linking of GG:RS promoted a significantly reduction on enzymatic degradation at both pH 1.2 and 6.8, which is a promising feature that can provide drug protection against premature degradation in the stomach. In contrast, GG:P microparticles cross-linked with calcium suffered high degradation at both pH values, an advantageous feature for quickly releasing drugs at different sites of the gastrointestinal tract. The high mucoadhesive ability of the microparticles was evidenced at both pH values, and the Freundlich parameters indicated stronger particle–mucin interactions at pH 6.8.

Ionotropic Gelation and Chemical Crosslinking as Methods for Fabrication of Modified-Release Gellan Gum-Based Drug Delivery Systems

“…LA gellan occurs as a result of the effect of alkaline hydrolysis. The LA gellan is broadly investigated as a component of oral drug delivery systems with the sustained or modified release [ 19 , 20 , 21 , 22 ]. In practice, the encapsulation of drugs into gellan gum matrices can be performed in two ways.…”

Oral pioglitazone HCl-loaded solid lipid microparticles: Formulation design and bioactivity studies

“…In addition, MPs could improve the water solubility of poorly soluble drugs, enhance their bioavailability, ensure controlled and sustained drug release (Khalifa and Abdul Rasool, 2017), and decrease drug toxicity (Oliveira et al, 2017). It was found that these carriers were promising in drugs protection and improving their stability (Boni et al, 2021), targeting the drug to a specific biological site, and reducing the number of doses, thereby improving patient adherence to treatment (Abdul Rasool et al, 2014;Bartos et al, 2021).…”

Poly(Lactic Acid)-Based Microparticles for Drug Delivery Applications: An Overview of Recent Advances

“…Recent advancements in microparticle manufacturing technology include procedures such as membrane emulsification (ME) [28], active self-healing encapsulation (ASE) [10], and micromechanical punching (MMP) for the fabrication of non-spherical microparticles [29]. Finally, ionotropic cross-linking [29], [30] and LbL-assembly [31], [32] are commonly used strategies in polysaccharide-based micro-sized drug delivery systems.…”