Controlled release from zein matrices: Interplay of drug hydrophobicity and pH

Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods: Caplets were prepared by hot-melt extrusion (HME) and injection moulding (IM). Each of the three model drugs were tested on two drug loadings in various dissolution media. The physical state of the drug, microstructure and hydration behaviour were investigated to build up understanding for the release behaviour from zein based matrix for drug delivery. Results: Drug crystallinity of the caplets increases with drug hydrophobicity. For ranitidine and indomethacin, swelling rates, swelling capacity and release rates were pH dependent as a consequence of the presence of charged groups on the drug molecules. Both hydration rates and release rates could be approached by existing models. Conclusion: Both the drug state as pH dependant electrostatic interactions are hypothesised to influence release kinetics. Both factors can potentially be used factors influencing release kinetics release, thereby broadening the horizon for zein as a tuneable release agent

Functional characterisation and antimicrobial efficiency assessment of smart nanohydrogels containing natamycin incorporated into polysaccharide-based films

The potential application of polysaccharide-based films containing smart nanohydrogels for the controlled release of food preservatives is demonstrated here. Smart active packaging is the most promising alternative to traditional packaging as it provides a controlled antimicrobial effect, which allows reducing the amount of preservatives in the food bulk, releasing them only on demand. This work evaluates the usefulness of smart thermosensitive poly(N-isopropylacrylamide) (PNIPA) nanohydrogels with or without acrylic acid (AA) incorporated into polysaccharide-based films (GA) to transport natamycin and release it as a response to environmental triggers. Release kinetics in liquid medium from GA films containing PNIPA/AA nanohydrogels (GA-PNIPA(5) and GA-PNIPA-20AA(5)) presented a characteristic feature regarding the films without nanohydrogels that was the appearance of a lag time in natamycin release, able to reach values of around 35 h. Another important feature of natamycin release kinetics was the fact that the release from GA-PNIPA/AA films only occurred when temperature was increased, so that the natamycin release was restricted to when there is a risk of growth of microorganisms that cause food spoilage or the development of pathogenic microorganisms. Additionally, it could be observed that the relative fraction of natamycin released from GA-PNIPA/AA films was significantly (p<0.05) higher than that released from GA films loaded with the same amount of free natamycin. It can be hypothesised that the encapsulation of natamycin into nanohydrogels helped it to be released from GA films, creating reservoirs of natamycin into the films and, therefore, facilitating its diffusion through the film matrix when the nanohydrogel collapses. In a solid medium, the low water availability limited natamycin release from GA-PNIPA/AA films restricting the on/off release mechanism of PNIPA/AA nanohydrogels and favouring the hydrophobic interactions between natamycin and polymer chains at high temperatures. Despite the low natamycin release in solid media, antimicrobial efficiency of GA-PNIPA(5) films containing natamycin in acidified agar plates was higher than that obtained with GA films without natamycin and GA films with free natamycin, probably due to the protecting effect against degradation when natamycin was included in the nanohydrogels, allowing its release only when the temperature increased.Clara Fucinos and Miguel A. Cerqueira are recipients of a fellowship (SFRH/BPD/87910/2012 and SFRH/BPD/72753/2010, respectively) from the Fundacao para a Ciencia e Tecnologia (FCT, POPH-QREN, and FSE Portugal). The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the project "BioInd - Biotechnology and Bioengineering for improved Industrial and Agro-Food processes", Ref. NORTE-07-0124-FEDER-000028 co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER and the project from the "Ministerio de Educacion y Ciencia" (Spain) "Nanohidrogeles inteligentes sensibles a cambios de pH y Temperatura: Diseno, sintesis y aplicacion en terapia del cancer y el envasado activo de alimentos", Ref. MAT2010-21509-C03-01

Chitosan encapsulation modulates the effect of capsaicin on the tight junctions of MDCK cells

Capsaicin has known pharmacological effects including the ability to reversibly open cellular tight junctions, among others. The aim of this study was to develop a strategy to enhance the paracellular transport of a substance with low permeability (FITC-dextran) across an epithelial cell monolayer via reversible opening of cellular tight junctions using a nanosystem comprised by capsaicin and of chitosan. We compared the biophysical properties of free capsaicin and capsaicin-loaded chitosan nanocapsules, including their cytotoxicity towards epithelial MDCK-C7 cells and their effect on the integrity of tight junctions, membrane permeability and cellular uptake. The cytotoxic response of MDCK-C7 cells to capsaicin at a concentration of 500 μM, which was evident for the free compound, is not observable following its encapsulation. The interaction between nanocapsules and the tight junctions of MDCK-C7 cells was investigated by impedance spectroscopy, digital holographic microscopy and structured illumination fluorescence microscopy. The nanocapsules modulated the interaction between capsaicin and tight junctions as shown by the different time profile of trans-epithelial electrical resistance and the enhanced permeability of monolayers incubated with FITC-dextran. Structured illumination fluorescence microscopy showed that the nanocapsules were internalized by MDCK-C7 cells. The capsaicin-loaded nanocapsules could be further developed as drug nanocarriers with enhanced epithelial permeability

Evaluation of water properties in HEA–HEMA hydrogels swollen in aqueous-PEG solutions using thermoanalytical techniques

Hydrogels are polymeric materials used in many pharmaceutical and biomedical applications due to their ability to form 3D hydrophilic polymeric networks, which can absorb large amounts of water. In the present work, polyethylene glycols (PEG) were introduced into the hydrogel liquid phase in order to improve the mechanical properties of hydrogels composed of 2-hydroxyethylacrylate and 2-hydroxyethylmethacrylate (HEA–HEMA) synthesized with different co-monomer compositions and equilibrated in water or in 20 % water–PEG 400 and 600 solutions. The thermoanalytical techniques [differential scanning calorimetry (DSC) and thermogravimetry (TG)] were used to evaluate the amount and properties of free and bound water in HEA–HEMA hydrogels. The internal structure and the mechanical properties of hydrogels were studied using scanning electron microscopy and friability assay. TG “loss-on-drying” experiments were applied to study the water-retention properties of hydrogels, whereas the combination of TG and DSC allowed estimating the total amount of freezable and non-freezing water in hydrogels. The results show that the addition of viscous co-solvent (PEG) to the liquid medium results in significant improvement of the mechanical properties of HEA–HEMA hydrogels and also slightly retards the water loss from the hydrogels. A redistribution of free and bound water in the hydrogels equilibrated in mixed solutions containing 20 vol% of PEGs takes place

Designing Bioactive Delivery Systems for Tissue Regeneration

The direct infusion of macromolecules into defect sites generally does not impart adequate physiological responses. Without the protection of delivery systems, inductive molecules may likely redistribute away from their desired locale and are vulnerable to degradation. In order to achieve efficacy, large doses supplied at interval time periods are necessary, often at great expense and ensuing detrimental side effects. The selection of a delivery system plays an important role in the rate of re-growth and functionality of regenerating tissue: not only do the release kinetics of inductive molecules and their consequent bioactivities need to be considered, but also how the delivery system interacts and integrates with its surrounding host environment. In the current review, we describe the means of release of macromolecules from hydrogels, polymeric microspheres, and porous scaffolds along with the selection and utilization of bioactive delivery systems in a variety of tissue-engineering strategies