Oral nanoparticles based on gellan gum/pectin for colon-targeted delivery of resveratrol.

Nanoparticles based on gellan gum/pectin blends were designed for colon-targeted release of resveratrol (RES). Their impact on drug release rates and permeability were evaluated using Caco-2 cell model and mucus secreting triple co-culture model. Polymeric nanoparticles (PNP) were successfully prepared by nebulization/ionotropic gelation, achieving high drug loading (>80%). PNP were spherical with a low positive charge density (+5mV) and exhibited diameters of around 330 nm. Developed PNP were able to promote effective modulation of drug release rates, so that only 3% of RES was released in acidic media over 2 h, and, in pH 6.8, the drug was released in a sustained manner, reaching 85% in 30 h. The permeability of RES-loaded PNP in the Caco-2 model was 0.15%, while in the triple co-culture model, in the presence of mucus, it reached 5.5%. The everted gut sac experiment corroborated the low permeability of RES-loaded PNP in the presence or absence of mucus and highlighted their high ability to interact with the intestinal tissue. Results indicate that the novel PNP developed in this work are safe and promising carriers for controlled delivery of RES at the colon.

Mucoadhesive films based on gellan gum/pectin blends as potential platform for buccal drug delivery.

Films of gellan gum:pectin blends were prepared by solvent casting method. Gellan gum:pectin mass ratios were varied (4:1; 1:1; 1:4) at different concentrations (3% or 4%) and glycerol was used as plasticizer (1 or 2%). The films were thin (18-30 µm), translucent, flexible, and homogeneous. The surface pH was suitable for buccal application. All films reached high mechanical resistance and the mucoadhesive ability of them was evidenced. High ratio of gellan gum improved the mechanical resistance and the mucoadhesion of the films as well as the control of drug release rates. The films did not disintegrate in simulate saliva up to 24 h and curcumin release could be sustained up to 12 h. The set of data evidence that the films designed in this work represent a potential platform for buccal drug delivery.

Gellan Gum/Pectin Beads Are Safe and Efficient for the Targeted Colonic Delivery of Resveratrol.

This work addresses the establishment and characterization of gellan gum:pectin (GG:P) biodegradable mucoadhesive beads intended for the colon-targeted delivery of resveratrol (RES). The impact of the polymer carrier system on the cytotoxicity and permeability of RES was evaluated. Beads of circular shape (circularity index of 0.81) with an average diameter of 914 µm, Span index of 0.29, and RES entrapment efficiency of 76% were developed. In vitro drug release demonstrated that beads were able to reduce release rates in gastric media and control release for up to 48 h at an intestinal pH of 6.8. Weibull's model correlated better with release data and b parameter (0.79) indicated that the release process was driven by a combination of Fickian diffusion and Case II transport, indicating that both diffusion and swelling/polymer chains relaxation are processes that contribute equally to control drug release rates. Beads and isolated polymers were observed to be safe for Caco-2 and HT29-MTX intestinal cell lines. RES encapsulation into the beads allowed for an expressive reduction of drug permeation in an in vitro triple intestinal model. This feature, associated with low RES release rates in acidic media, can favor targeted drug delivery from the beads in the colon, a promising behavior to improve the local activity of RES.

A novel pH-responsive hydrogel-based on calcium alginate engineered by the previous formation of polyelectrolyte complexes (PECs) intended to vaginal administration.

This work aimed to develop a calcium alginate hydrogel as a pH responsive delivery system for polymyxin B (PMX) sustained-release through the vaginal route. Two samples of sodium alginate from different suppliers were characterized. The molecular weight and M/G ratio determined were, approximately, 107 KDa and 1.93 for alginate_S and 32 KDa and 1.36 for alginate_V. Polymer rheological investigations were further performed through the preparation of hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the acquisition of pseudoplastic viscous system able to acquiring a differential structure in simulated vaginal microenvironment (pH 4.5). The PMX-loaded hydrogel (hydrogel_PMX) was engineered based on polyelectrolyte complexes (PECs) formation between alginate and PMX followed by crosslinking with calcium chloride. This system exhibited a morphology with variable pore sizes, ranging from 100 to 200 µm and adequate syringeability. The hydrogel liquid uptake ability in an acid environment was minimized by the previous PECs formation. In vitro tests evidenced the hydrogels mucoadhesiveness. PMX release was pH-dependent and the system was able to sustain the release up to 6 days. A burst release was observed at pH 7.4 and drug release was driven by an anomalous transport, as determined by the Korsmeyer-Peppas model. At pH 4.5, drug release correlated with Weibull model and drug transport was driven by Fickian diffusion. The calcium alginate hydrogels engineered by the previous formation of PECs showed to be a promising platform for sustained release of cationic drugs through vaginal administration.

Cellulose triacetate films obtained from sugarcane bagasse: Evaluation as coating and mucoadhesive material for drug delivery systems.

Cellulose triacetate (CTA) films were produced from cellulose extracted from sugarcane bagasse. The films were characterized using scanning electron microscopy (SEM), water vapor permeability (WVP), mechanical properties (MP), enzymatic digestion (ED), and mucoadhesive properties evaluation (MPE). WVP showed that more concentrated films have higher values; asymmetric films had higher values than symmetric films. MP showed that symmetric membranes are more resistant than asymmetric ones. All films presented high mucoadhesiveness. From the WVP and MP results, a symmetric membrane with 6.5% CTA was selected for the coating of gellan gum (GG) particles incorporating ketoprofen (KET). Thermogravimetric analysis (TGA) showed that the CTA coating does not influence the thermal stability of the particles. Coated particles released 100% of the KET in 24h, while uncoated particles released the same amount in 4h. The results highlight the CTA potential in the development of new controlled oral delivery systems.

Gellan gum microspheres crosslinked with trivalent ion: effect of polymer and crosslinker concentrations on drug release and mucoadhesive properties.

Gellan gum microspheres were obtained by ionotropic gelation technique, using the trivalent ion Al(3+). The percentage of entrapment efficiency ranged from 48.76 to 87.52% and 2(2) randomized full factorial design demonstrated that both the increase of polymer concentration and the decrease of crosslinker concentration presented a positive effect in the amount of encapsulated drug. Microspheres size and circularity ranged from 700.17 to 938.32 µm and from 0.641 to 0.796 µm, respectively. The increase of polymer concentration (1-2%) and crosslinker concentration (3-5%) led to the enlargement of particle size and circularity. However, the association of increased crosslinker concentration and reduced polymer content made the particles more irregular. In vitro and ex vivo tests evidenced the high mucoadhesiveness of microspheres. The high liquid uptake ability of the microspheres was demonstrated and the pH variation did not affect this parameter. Drug release was pH dependent, with low release rates in acid pH (42.40% and 44.93%) and a burst effect in phosphate buffer pH (7.4). The Weibull model had the best correlation with the drug release data, demonstrating that the release process was driven by a complex mechanism involving the erosion and swelling of the matrix or by non-Fickian diffusion.

Mucoadhesive beads of gellan gum/pectin intended to controlled delivery of drugs.

Gellan gum/pectin beads were prepared by ionotropic gelation, using Al(3+) as crosslinker. High yield (92.76%) and entrapment efficiency (52.22-88.78%) were reached. Beads exhibited high circularity (0.730-0.849) and size between 728.95 and 924.56 µm. Particle size and circularity was increased by raising polymer and crosslinker concentrations. Polymers ratio did not influence beads properties. The materials stability and the absence of drug-polymers interactions were evidenced by thermal analysis and FTIR. The high beads mucoadhesiveness was evidenced by in vitro and ex vivo tests. The erosion of beads was greater in acid media while swelling was more pronounced in pH 7.4. Drug release was dependent on pH in which samples 11H1-3, 11H1-5 and 41H1-3 released only 34%, 20% and 22% of ketoprofen in pH 1.2, while in pH 7.4 the drug release was sustained up to 360 min. Korsmeyer-Peppas model demonstrated that drug release occurred according to super case-II transport.

Preparation and characterization of free films of high amylose/pectin mixtures cross-linked with sodium trimetaphosphate.

High amylose and pectin were mixed at 1:1 mass ratio and cross-linked with sodium trimetaphosphate (STMP) in alkaline medium. Films were prepared from aqueous dispersions of these cross-linked polymer blend at three different concentrations (3, 4 and 5%), by solvent casting method. Characterization of the films included thickness, surface morphology, water uptake, water vapor permeability (WVP), tensile strength measurements and enzymatic digestion. The cross-linking allowed to obtain films with improved mechanical properties and reduced WVP. The high resistance to enzymatic digestion exhibited by these films represents a promising approach to their application in the development of colon drug delivery systems.