P. Cerezo

Biopolymer–clay nanocomposites for controlled drug delivery

Abstract Polymer–clay nanocomposites have attracted great attention worldwide from both academic and industrial points of view. This review aims at reporting on very recent developments in types of polymer–clay nanocomposites, their constituents, synthetic routes, properties and their uses as carriers for drug delivery. This new family of composite materials frequently exhibits remarkable improvements of material properties when compared with the matrix polymers alone or conventional micro- and macrocomposites. Pharmaceutically, interesting improvements include increased mechanical and rheological properties, reduced drug permeability and water uptake and controlled release characteristics. On the basis of these properties, polymer–clay nanocomposites are extending their applicability to the design of new drug release dosage forms with highly specific technological and biopharmaceutical properties, such as swelling, film forming, bioadhesion, and cell uptake. Overall, there is an essential requirement directed towards a more comprehensive understanding of the supramolecular structure, drug loading and release mechanisms of these hybrid materials.

Montmorillonite-chitosan-silver sulfadiazine nanocomposites for topical treatment of chronic skin lesions: in vitro biocompatibility, antibacterial efficacy and gap closure cell motility properties.

Silver compounds and especially silver sulfadiazine (AgSD) are reported as effective antimicrobial agents against almost all known bacteria, fungi and some viruses. However, AgSD has been shown to be cytotoxic toward fibroblasts and keratinocytes in vitro and consequently to retard wound healing in vivo. The aim of the present work was to evaluate the in vitro biocompatibility (cytotoxicity and proliferation), antimicrobial efficacy and cell motility gap closure (assay of wound closure) of MT/CS nanocomposites loaded with silver sulfadiazine (AgSD). It is envisioned to be administered as a powder or a dressing for cutaneous application in the treatment of skin ulcers. The loading of AgSD in MT/CS nanocomposites aimed at preventing the delay in wound healing, by decreasing the cytotoxicity of AgSD and maintaining its antimicrobial properties. Nanocomposites were prepared by using different amounts of MT (100-2000 mg) and 40 ml of a 1% (w/w) chitosan glutamate aqueous solution. The relative amounts of AgSD and chitosan in the systems were assessed by suitable analytic methods. The nanocomposite prepared using 100mg of MT was characterized for in vitro biocompatibility and proliferation and for wound healing using normal human dermal fibroblasts (NHDF). Antimicrobial properties were evaluated against four reference bacterial strains: Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa. AgSD loaded in the 100 MT/CS nanocomposite showed good in vitro biocompatibility and gap closure properties (fibroblasts) and maintained AgSD antimicrobial properties, especially against P. aeruginosa, that often complicates skin lesions.

Solid state characterisation of silver sulfadiazine loaded on montmorillonite/chitosan nanocomposite for wound healing.

Biopolymer chitosan/montmorillonite nanocomposites loaded with silver sulfadiazine for wound healing purposes were prepared via intercalation solution technique. Structure and morphology of loaded nanocomposites were studied and compared with pure components and unloaded nanocomposites. X-ray diffraction, Fourier transformed infrared spectroscopy, high resolution transmission electron microscopy coupled with energy-dispersion X-ray analysis, thermal and elemental analysis were employed for the characterisation. The results confirmed that the drug was effectively loaded in the three-dimensional nanocomposite structures, in which chitosan chains were adsorbed in monolayers into the clay mineral interlayer spaces.

Release kinetics of 5-aminosalicylic acid from halloysite

This paper investigates desorption of 5-aminosalicilyc acid (5-ASA) adsorbed onto halloysite (HL). Desorption isotherms were fitted according to kinetic laws obtained considering release of 5-ASA from HL as the phase of desorption of the previously adsorbed drug molecules both inside the nanotubes of HL as onto the surface of clay particles and/or in the inter-particle spaces of their aggregates. Desorption isotherms has been also fitted with other equations frequently used in drug release kinetics studies. The best fitting corresponded to the kinetic model proposed; in agreement with the results of adsorption.

Supramolecular structure of 5-aminosalycilic acid/ halloysite composites

This paper assesses the supramolecular structure of nanocomposites prepared by including the anti-inflammatory drug 5-aminosalycilic acid in halloysite nanotubes. Halloysite tubes have sub-micron individual lengths with outer diameters ∼0.1 µm, as observed by FESEM. The mercury intrusion plots showed bimodal profiles with pore dimensions ∼10 and 0.06 µm. X-ray diffraction and thermogravimetric results revealed changes in the hydration form of the clay after the interaction. The groups associated to the interaction were studied by FTIR. The location of the drug in the composites was determined after uranium staining of its amino groups by X-EDS microanalysis coupled with HREM. The drug was located both inside and on the surface of the halloysite nanotubes. These results confirm the occurrence of two concomitant interaction mechanisms: rapid adsorption of 5-ASA at the external halloysite surface followed by slow adsorption of the drug inside the tubes.

Intestinal permeability of oxytetracycline from chitosan-montmorillonite nanocomposites

A nanocomposite based on chitosan and montmorillonite was developed as carrier to improve oral bioavailability of oxytetracycline. The nanocomposite was prepared by simple solid-liquid interaction and loaded with the drug. The loaded nanocomposite was characterized by X-ray powder diffraction, thermal analysis, FTIR spectroscopy and zeta potential. Caco-2 cell cultures were used to evaluate in vitro cytotoxicity and drug permeation. Confocal laser scanning microscopy was also performed to evaluate the eventual entrapment of drug into the Caco-2 cells. Results showed that the nanocomposite was internalized into the cells and effectively enhanced drug permeation, being also biocompatible towards Caco-2 cells.

One-dimensional filtration of pharmaceutical grade phyllosilicate dispersions

The filtration behaviour of some clay-water dispersions was studied. Two Spanish fibrous phyllosilicates (sepiolite from Vicálvaro and palygorskite from Turón) and a commercial bentonite (Bentopharm UK) with similar sizes and different morphologies (fibrous and/or laminar) were selected as model clays. Sepiolite from Vicálvaro is an almost pure fibrous sample, Bentopharm presents a high amount of laminar particles and palygorskite from Turón is made up of similar percentages of laminar and fibrous particles. The disperse systems were made up using a rotor-stator mixer working at two different mixing rates (1000 and 8000 rpm), for periods of 1 and 10 min. Filtration measurements were taken and the corresponding filtration curves obtained. Finally, the desorptivity (S) of the filtration cakes was calculated and correlated to the textural characteristics of the materials, the solid fraction and mixing conditions. Filtration behaviour of the dispersions depended on all three of these factors. Laminar dispersions presented lower S values than fibrous dispersions. In the 2% w/v dispersions the bridging forces between particles did not permit formation of an interconnected network as in 10% w/v dispersions and, consequently, filtration times increased with the solid fraction (i.e. S values decreased). Regarding stability to pH changes, the results showed that filtration behaviour was highly sensitive to basic pH in the fibrous clay dispersions and almost insensitive in the laminar clay dispersions.

Mathematical models describing drug release from biopolymeric delivery systems

Abstract This review focuses on the mathematical models that have been proposed to explain drug release from biopolymeric delivery systems, designed to modify release of the administered doses. Drug release from these systems is controlled by different mechanisms that include drug diffusion, drug and/or polymer dissolution and, in some cases, polymer swelling and erosion processes, among others. Consequently, mathematical modelling of drug release profiles from these systems is a complex topic. The underlying theories and the equations of the principal proposed approaches are considered, including classical empirical and semiempirical models and mechanistic theories that consider biopolymer behaviour during the release process. Advantages and limitations of each model are discussed and their prediction abilities are provided.

Use of water uptake and capillary suction time measures for evaluation of the anti-diarrhoeic properties of fibrous clays

This study explores the use of water sorption/retention measures as alternative methodologies to the official methylene blue adsorption test for the evaluation of the anti-diarrhoeic properties of some fibrous clay. Three fibrous phyllosilicates—palygorskite from Ciudad Real (PCR), and sepiolite from Vicalvaro (SV) and Yunclillos (SY)—have been studied. Two commercial anti-diarrhoeal products—Pharmasorb Colloidal© (PHC) and Pharmasorb Regular© (PHR)—each mainly consisting of palygorskite, were also included in the study. The 75–125-μm sieve fraction was selected and methylene blue adsorption (MBA) capacity and water uptake characteristics—total amount of water retained (Qmax) and water uptake velocities (Iw)—measured. Finally, the water retention capacity, with dispersions of 10% w/v, was assessed by means of capillary suction measures (CST). MBA capacity was similar for all the samples, with PHC showing the highest capacity to adsorb the dye. PHC was also the sample which retained the most water (Qmax>2.5 mg/mg), followed by PCR and PHR (Qmax≈1.5 mg/mg) and finally SV and SY (Qmax 160 s) was almost twice those of the rest of studied materials. A linear correlation was found between the amount of palygorskite in PCR, PHC and PHR and their water uptake capacities. This was not possible for the sepiolite samples. An inverse correlation was found between velocity of water suction (Iw) and capacity of methylene blue adsorption. Water uptake and water retention measures are proposed as complementary to the methylene blue adsorption assay in the evaluation as anti-diarrhoeics of the studied materials.

Pharmaceutical and Cosmetic Uses of Fibrous Clays

Abstract Clays are ubiquitous substances, some of which (talcum, kaolinite, smectites, fibrous clays) have been used since very ancient times for their therapeutic effects. This chapter focuses on the use of fibrous clays (sepiolite and palygorskite or attapulgite) as active components and/or excipients in pharmaceutical formulations and cosmetics. In particular, they exhibit antidiarrhoeal and antacid activity when administered orally as solid and liquid preparations (tablets and suspensions). Fibrous clays are also used as adsorbents and protectors in topical and systemic formulations in the treatment of, for example, acne, leg ulcers, inflammatory bowel disease and renal failure. Palygorskite and sepiolite are used worldwide as excipients in non-parenteral licenced medicines and are included in the FDA Inactive Ingredient Guide for oral solid dosage forms (powders and tablets). They fulfil several functional categories of excipients, including diluents, glidants, disintegrants and adsorbents. In liquid and semi-solid preparations, fibrous clays act as suspending agents to prevent settling and separation in liquid medications. Palygorskite and sepiolite are mainly used in cosmetic products to give the skin opaqueness, eliminate shine and cover up imperfections. They are also employed as deodorants, in dry shampoos and bath powders to absorb humidity and odours, avoiding skin irritation. Finally, apart from these traditional applications, fibrous clays have been also described as drug carriers in modified drug delivery systems.