Development and in vitro/in vivo evaluation of Zn-pectinate microparticles reinforced with chitosan for the colonic delivery of progesterone

Abstract

The colon is a promising target for drug delivery owing to its long transit time of up to 78 h, which is likely to increase the time available for drug absorption. Progesterone has a short elimination half-life and undergoes extensive first-pass metabolism, which results in very low oral bioavailability ($25%). To overcome these shortcomings, we developed an oral multiparticulate system for the colonic delivery of progesterone. Zn-pectinate/chitosan microparticles were prepared by ionotropic gelation and characterized for their size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling behavior. The effect of crosslinking pH, cross-linking time and chitosan concentration on progesterone release were also studied. Spherical microparticles having a diameter of 580-720 mm were obtained. Drug entrapment efficiency of $75-100% was obtained depending on the microparticle composition. Microparticle mucoadhesive properties were dependent on the pectin concentration, as well as the cross-linking pH. Progesterone release in simulated gastric fluids was minimal (3-9%), followed by burst release at pH 6.8 and a sustained phase at pH 7.4. The in vivo study revealed that the microparticles significantly increased progesterone residence time in the plasma and increased its relative bioavailability to $168%, compared to the drug alone. This study confirms the potential of Zn-pectinate/chitosan microparticles as a colon-specific drug delivery system able to enhance the oral bioavailability of progesterone or similar drugs.

Investigation of the parameters affecting the release of flurbiprofen from chitosan microspheres

“…Its biodegradation products are harmless amino sugars that can be absorbed by the body (Hejazi, Amiji, 2003). Chitosan is widely used to prepare particular drug delivery systems such as microparticules (Yuan, Chessnut, Utturkar, 2007;Ma, Liu, 2010;Park, Lee, Lee, 2012;Caetano, Almeida, Gonçalves, 2016;Gadalla et al, 2016;Jeon et al, 2016).…”

A Colon Targeted Delivery System for Resveratrol Enriching in pH Responsive-Model

“…It was reported that the EE of progesterone loaded pectin-zinc-chitosan in the concentrations of 1, 4, 4, and 1 % w/v was around 75 % with the size of 500-700 µm. 20 EE of albumin in pectin-chitosan complex was around 58-73%.…”

“…14 Most of reported pectin-chitosan complexes for colon specific delivery were in the form of visible bead or capsule which were not suitable for food and beverages. [15][16][17][18][19][20] The main concern of future food industry is enriching food and beverages with bioactive components in natural matrix for specific purpose. 21 Therefore, development of micro-or nano-particles as colloidal suspension is a priority.…”

Development and in Vitro Evaluation of Polysaccharide-Based System for Intestinal Delivery of Azathioprine for Treatment of Gastroduodenal Crohn’s Disease, Jejunoileitis and Ileitis

“…EE of the beads prepared of 8% pectin solution was higher than that of the beads prepared at 4% pectin, indicating the probability of formation of denser bead wall that prevent the drug escape from the beads matrix during processing and washing steps ( Table 2). [37] The amount of drug released in the gastric simulating medium from the beads prepared at higher pectin concentration (39 ± 1.1%) was significantly less than those released from the beads prepared of lower concentration (50.6 ± 0.5%) confirming the incidence of denser cross-linking of pectin due to the higher polymers content (Figure 3) [34,37] Therefore, using higher pectin concentration (B3) was more appropriate for the desired goal than lower pectin concentration. …”

“…For illustration, the sphericity is evaluated in terms of circularity and roundness (i.e. In case of typical sphere the values of circularity and roundness equal one) [33,34]. Both preparation methods formed beads in similar yield values, whereas DL and EE of the beads prepared by the first preparation method (A1) were less than those of the beads prepared by the second preparation method (B1) ( Table 2).…”