Felipe Oyarzun-Ampuero

Lipid nanoparticles for the topical delivery of retinoids and derivatives

Retinoids are lipophilic compounds that are highly used in cosmetics/therapeutics for skin disorders. Conventional formulations are limited by poor water solubility, high chemical/photochemical instability and the irritation of retinoids. Interestingly, lipid nanoparticles enable the administration of retinoids in aqueous media, providing drug stabilization and controlled release. Recently, it has been demonstrated that retinoids in solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules can decrease degradation, improve targeting and enhance efficacy for the treatment of skin disorders. This article focuses on the formulation, fabrication, characterization and in vitro/in vivo evaluation of solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules loaded with retinoids for skin administration. Furthermore, the incorporation of these lipid nanoparticles into secondary vehicles is discussed.

Flow Chemistry to Control the Synthesis of Nano and Microparticles for Biomedical Applications

In this article we review the flow chemistry methodologies for the controlled synthesis of different kind of nano and microparticles for biomedical applications. Injection mechanism has emerged as new alternative for the synthesis of nanoparticles due to this strategy allows achieving superior levels of control of self-assemblies, leading to higher-ordered structures and rapid chemical reactions. Self-assembly events are strongly dependent on factors such as the local concentration of reagents, the mixing rates, and the shear forces, which can be finely tuned, as an example, in a microfluidic device. Injection methods have also proved to be optimal to elaborate microsystems comprising polymer solutions. Concretely, extrusion based methods can provide controlled fluid transport, rapid chemical reactions, and cost-saving advantages over conventional reactors. We provide an update of synthesis of nano and microparticles such as core/shell, Janus, nanocrystals, liposomes, and biopolymeric microgels through flow chemistry, its potential bioapplications and future challenges in this field are discussed.

Photochromic Solid Materials Based on Poly(decylviologen) Complexed with Alginate and Poly(sodium 4-styrenesulfonate)

Photochromic solid materials based on the cationic polymer poly(decylviologen) are reported. The solids were obtained by freeze-drying colloidal suspensions of nanocomplexes obtained by mixing aqueous solutions of the polycation with different solutions of polyanions such as poly(sodium 4-styrenesulfonate) or sodium alginate, at a cationic/anionic polymeric charge ratio of 0.7. The photochromic responses of the solid materials fabricated with alginate as complementary charged polyelectrolyte of the cationic polyviologen are faster than those of the solid materials fabricated with poly(sodium 4-styrenesulfonate), achieving coloration kinetics in the order of minutes, and discoloration kinetics in the order of hours for the former. Aromatic-aromatic interactions between the latter polyanion and the polyviologen may stabilize the dicationic form of the viologen derivative, increasing the necessary energy to undergo photoreduction, thus decreasing the reduction kinetics.

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.

Organic and Inorganic Nanoparticles for Prevention and Diagnosis of Gastric Cancer.

Organic and inorganic nanoparticles show great potential for cancer diagnosis and treatment. Because gastric cancer (GC) represents the second most deadly type of neoplasia worldwide, continued research efforts by scientists and clinicians are essential to improve diagnosis and treatment. This paper reviews significant findings in the area of nanoparticles (organic and inorganic origin) that may aid in prevention and diagnosis of GC. This review focuses in the first section on H. pylori and the connection to GC, highlighting nanoformulations designed to control bacterial growth. The second section evaluates the potential of different imaging techniques (especially using inorganic nanoparticles) in the detection of GC, and the third section summarizes how nanotechnology may be employed in the analytical detection of GC biomarkers (metallic plasmons, electrochemical biosensors and colorimetric sensors). We foresee that the prevention and diagnosis of GC will require the development of complex collaborative studies. Additionally, scientists also need to be tightly connected to industry in order to facilitate upscaling and rapid transfer of promising products to the clinic.

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.

Facile Formation of Redox-Active Totally Organic Nanoparticles in Water by In Situ Reduction of Organic Precursors Stabilized through Aromatic–Aromatic Interactions by Aromatic Polyelectrolytes

The formation of redox-active, totally organic nanoparticles in water is achieved following a strategy similar to that used to form metal nanoparticles. It is based on two fundamental concepts: i) complexation through aromatic-aromatic interactions of a water-soluble precursor aromatic molecule with polyelectrolytes bearing complementary charged aromatic rings, and ii) reduction of the precursor molecule to achieve stabilized nanoparticles. Thus, formazan nanoparticles are synthesized by reduction of a tetrazolium salt with ascorbic acid using polyelectrolytes bearing benzene sulfonate residues of high linear aromatic density, but cannot be formed in the presence of nonaromatic polyelectrolytes. The red colored nanoparticles are efficiently encapsulated in calcium alginate beads, showing macroscopic homogeneity. Bleaching kinetics with chlorine show linear rates on the order of tenths of milli-meters per minute. A linear behavior of the dependence of the rate of bleaching on the chlorine concentration is found, showing the potential of the nanoparticles for chlorine sensing.

Novel Nanostructured Polymeric Carriers to Enable Drug Delivery for Cardiovascular Diseases.

Applications of polymeric nanotechnologies for enabling therapies for cardiovascular diseases have shown recent success. Both intravenous and oral administration have been investigated and achieved different degrees of development. While circulating polymeric nanostructured carriers are subjected to a number of interactions, smart nanoparticle design has enabled the formulation of active molecules to be delivered to specific targets for cardiovascular effects. This review aims at outlining the multiple factors that can affect the fate of polymeric nanostructured carriers in systemic circulation. With an understanding of these factors, the literature on the various polymeric nanostructured carriers is reviewed. Finally, the emerging uses of nanotechnology to formulate orally administered drugs for cardiovascular diseases are depicted.

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.