Sandra L. Orellana

Nanoparticles for the Treatment of Wounds

The treatment of skin wounds represents an important research area due to the important physiological and aesthetic role of this tissue. During the last years, nanoparticles have emerged as important platforms to treat skin wounds. Silver, gold, and copper nanoparticles, as well as titanium and zinc oxide nanoparticles, have shown potential therapeutic effects on wound healing. Due to their specific characteristics, nanoparticles such as nanocapsules, polymersomes, solid lipid nanoparticles, and polymeric nanocomplexes are ideal vehicles to improve the effect of drugs (antibiotics, growth factors, etc.) aimed at wound healing. On the other hand, if active excipients are added during the formulation, such as hyaluronate or chitosan, the nanomedicine could significantly improve its potential. In addition, the inclusion of nanoparticles in different pharmaceutical materials may enhance the beneficial effects of the formulations, and allow achieving a better dose control. This paper aims at reviewing significant findings in the area of nanoparticles and wound treatment. Among the reviewed topics, we underline formulations comprising inorganic, polymeric, surfactant self-assembled, and lipid nanosystems. Among the drugs included in the nanoformulations, the paper refers to antibiotics, natural extracts, proteins, and growth factors, among others. Finally, the paper also addresses nanoparticles embedded in secondary vehicles (fibers, dressings, hydrogels, etc.) that could improve their application and/or upgrade the release profile of the active.

Therapeutic potential of a low-cost device for wound healing: a study of three cases of healing after lower-extremity amputation in patients with diabetes.

Diabetic foot ulcers constitute a tremendous challenge for patients, caregivers, and health care systems. The high incidence and high financial costs associated with their treatment have transformed them in a health and economic worldwide problem. The increase in population life expectancy and lifestyle changes have facilitated the spreading of diabetes, rising diabetic foot ulcer incidence. Only 60%–80% of the patients achieve healing of ulcers, and the incidence of a second ulcer, in the same or different site of the foot that has had a previous ulcer, is approximately 50% in 2–5 years. In addition, ulcers with duration longer than 4 weeks are commonly associated with bad results in healing and an increased risk of amputation. Three patients with type 2 diabetes mellitus have been subjected to treatment with NL.1.2, a low-cost, biocompatible solid device that presented pro-angiogenic properties. The selected patients had undergone amputation, and their wounds, classified as Wagner II, did not show a significant progress in healing after a period of 2–5 months before treatment with NL.1.2. Complete closure of their wounds was achieved in 42–60 days.

Association Efficiency of Three Ionic Forms of Oxytetracycline to Cationic and Anionic Oil-In-Water Nanoemulsions Analyzed by Diafiltration

The association efficiency of oxytetracycline (OTC) to pharmaceutical available, ionic oil-in-water nanoemulsions is studied. Theoretical mathematical developments allowed us to differentiate by diafiltration (DF) between thermodynamically and kinetically controlled binding of the drug to the nanoemulsions, and relate these important magnitudes to the association efficiency. The nanoemulsions have been prepared by the solvent displacement technique in the presence of cationic and anionic surfactants. The resulting nanoemulsions were stable at 4°C and 25°C for 60 days, have a size of ∼ 200 nm, showing polydispersity indexes ranging between 0.11 and 0.23, and present zeta potentials ranging between -90 and +60 mV, depending on the charge of the surfactants used. The zeta potential of the nanoemulsions influenced the interaction with OTC, having three ionic forms at different pH, namely, cationic, zwitterionic, and anionic. DF proved to be a powerful tool for the quantification of the drug association efficiency, achieving values up to 84%. Furthermore, this technique allowed obtaining different values of the drug fractions reversibly bound (11%-57%) and irreversibly bound (10%-40%) to the nanoemulsions depending on the surfactants used and pH. These findings may be useful for the development of new drug delivery systems, and as routine assays in academia and pharmaceutical industries.

Aerogels made of chitosan and chondroitin sulfate at high degree of neutralization: Biological properties toward wound healing: AEROGELS OF CS AND ChS NANOCOMPLEXES

In this study, highly neutralized, highly porous, and ultralight polymeric aerogels prepared from aqueous colloidal suspensions of chitosan (CS) and chondroitin sulfate (ChS) nanocomplexes, formulated as quasi-equimolar amounts of both, are described. These aerogels were designed as healing agents under the inspiration of minimizing the amount of matter applied to wounds, reducing the electrostatic potential of the material and avoiding covalent cross-linkers in order to decrease metabolic stress over wounds. Aerogels synthesized under these criteria are biocompatible and provide specific properties for the induction of wound healing. They do not affect neither the metabolic activity of cultured 3T3 fibroblasts nor the biochemical parameters of experimental animals, open wounds close significantly faster and, unlike control wounds, complete reepithelialization and scarring can be attained 14 days after surgery. Because of its hydration abilities, rapid adaptation to the wound bed and the early accelerator effect of wound closure, the CS/ChS aerogels appear to be functional inducers of the healing. Previous information show that CS/ChS aerogels improve wound bed quality, increase granulation tissue and have pain suppressive effect. CS/ChS aerogels are useful as safe, inexpensive and easy to handle materials for topical applications, such as skin chronic wounds.

Chitosan/chondroitin sulfate aerogels with high polymeric electroneutralization degree: formation and mechanical properties

Abstract The formation of ultralight, highly porous solid materials (porosity higher than 99%) containing equivalent molar amounts of chitosan (CS) and chondroitin sulfate (ChS) is presented. First, we show protocols to produce colloidal suspensions of assembled polymer nanocomplexes by simultaneously mixing equimolar amounts of the oppositely charged polysaccharides, preventing macroprecipitation. The colloidal suspensions were then freeze-dried to form the active aerogels. Apparent density in the order of 100–101 mg/cm3 was achieved. The materials show low stiffness (Young’s modulus of about 2 kPa), which make them easy to handle for clinical applications, and easy to compress, pack, store and transport. These characteristics promote them as cheap, safe and biodegradable materials able to be used for several therapeutic purposes, such as wound healing.

Antibacterial activity against Staphylococcus aureus of chitosan/chondroitin sulfate nanocomplex aerogels alone and enriched with erythromycin and elephant garlic (Allium ampeloprasum L. var. ampeloprasum) extract

Abstract The antibacterial activity against Staphylococcus aureus of aerogels fabricated from colloidal suspensions of chitosan/chondroitin sulfate nanocomplexes is analyzed. Upon freeze-drying the colloidal suspensions, the aerogels presented a porous structure made of microsheets and microfibers. The aerogels could, in addition, be loaded with antimicrobial agents. Loaded with the antibiotic erythromycin, the aerogels showed crystalline deposits, affecting the topography of the samples as well as their mechanical properties, showing a decrease on the apparent Young’s modulus and hardness at 40% deformation. Loaded with elephant garlic (Allium ampeloprasum L. var. ampeloprasum) extract, the aerogels showed texturization of the microsheets and microfibers, and the higher relative mass allowed an increase on the apparent Young’s modulus and hardness at 40% deformation with respect to pristine aerogels. Unloaded aerogels showed activity against Staphylococcus aureus, including a methicillin-resistant strain. The release of erythromycin from the aerogels to an agar environment is governed by equilibrium forces with the polysaccharides, which allow modulating the load of antibiotic and its concomitant diffusion from the material. The diffusion of the active components of the elephant garlic extract did not show a dependence on the polysaccharide content, revealing a week interaction. The elephant garlic extract resulted active against the methicillin-resistant Staphylococcus aureus strain, while resistance was found for the antibiotic, revealing the therapeutic potential of the natural extract. The antimicrobial aerogels may be used for several therapeutic purposes, such as healing of infected chronic wounds.

Dispersion of the Photosensitizer 5,10,15,20-Tetrakis(4-Sulfonatophenyl)-porphyrin by the Amphiphilic Polymer Poly(vinylpirrolidone) in Highly Porous Solid Materials Designed for Photodynamic Therapy

The ability of the amphiphilic and biocompatible poly(vinylpyrrolidone) to avoid self-aggregation of the photosensitizer 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin in aqueous solution in the presence of the biocompatible polycation chitosan, polymer that induces the dye self-aggregation, is shown. This is related to the tendency of the dye to undergo preferential solvation by the amphiphilic polymer. Importantly, the dispersant ability of this polymer is transferred to the solid state. Thus, aerogels made of the biocompatible polymers chitosan and chondroitin sulfate, and containing the photosensitizer dispersed by the amphiphilic polymer have been synthesized. Production of reactive oxygen species by the aerogel containing the amphiphilic polymer was faster than when the polymer was absent, correlating with the relative concentration of dyes dispersed as monomers. The aerogels presented here constitute low cost biocompatible materials bearing a conventional photosensitizer for photodynamic therapy, easy to produce, store, transport, and manage in clinical practice.