Microbicidal Polymer Nanoparticles Containing Clotrimazole for Treatment of Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) alters the innate cervicovaginal immunity, which provides an important barrier against viruses and other infections. The incidence of this disease has not decreased in the last 30 years, so effective treatments are still needed. Nanoparticles (NPs) of cellulose acetate phthalate (CAP) and clotrimazole (CLZ) were prepared by the emulsification-diffusion method. NPs were characterized using dynamic light scattering, atomic force microscopy and differential scanning calorimetry; their release profile was determined by the dialysis bag technique and mucoadhesion was evaluated with the mucin-particle method. The growth inhibition study of Candida albicans was carried out using the plate counting technique. Finally, accelerated physical stability tests of NPs were carried out, both in water and in SVF. The CAP-CLZ NPs had an average diameter of 273.4 nm, a PDI of 0.284, smooth surfaces and spherical shapes. In vitro release of CLZ from the CAP NPs was categorized with the Weibull model as a matrix system in which initial release was rapid and subsequently sustained. The inhibition of C. albicans growth by the CAP-CLZ NPs was greater than that of free CLZ, and the CAP-only NPs had a microbicidal effect on C. albicans. The NPs showed poor mucoadhesiveness, which could lead to studies of their mucopenetration capacities. An accelerated physical stability test revealed the erosion of CAP in aqueous media. A nanoparticulate system was developed and provided sustained release of CLZ, and it combined an antifungal agent with a microbial polymer that exhibited antifungal activity against C. albicans.

Trends in biopolymer science applied to cosmetics.

The term biopolymer refers to materials obtained by chemically modifying natural biological substances or producing them through biotechnological processes. They are biodegradable, biocompatible and non-toxic. Due to these advantages, biopolymers have wide applications in conventional cosmetics and new trends and have emerged as essential ingredients that function as rheological modifiers, emulsifiers, film-formers, moisturizers, hydrators, antimicrobials and, more recently, materials with metabolic activity on skin. Developing approaches that exploit these features is a challenge for formulating skin, hair and oral care products and dermatological formulations. This article presents an overview of the use of the principal biopolymers used in cosmetic formulations and describes their sources, recently derived structures, novel applications and safety aspects of the use of these molecules.

Le terme biopolymère fait référence aux matériaux obtenus par modification chimique des substances biologiques naturelles ou ceux qui surviennent des processus biotechnologiques. Ils sont biodégradables, biocompatibles, et non-toxiques. Du à leur avantages, les biopolymères ont de larges applications dans les cosmétiques conventionnels ainsi que dans les nouvelles tendances, et se placent comme des ingrédients essentiels qui peut être utilise comme modificateurs rhéologiques, émulsifiants, producteurs de films, humectants, hydratants, antimicrobiens, et, plus récemment, comme matériaux avec activité métabolique sur la peau. Le développement d'approches compte tenu de ces caractéristiques constitue un défi pour la création de produits de soins capillaires, dermatologiques et buccodentaires. Cet article présente une vision sur l'utilisation des principaux biopolymères dans les produits cosmétiques, et décrit leurs sources, leur structures dérivées, les nouvelles applications, ainsi que les aspects de sécurité lies à leur utilisation comme molécules cosmétiques.

Neopeltolide and its synthetic derivatives: a promising new class of anticancer agents.

Being the first or second cause of death worldwide, cancer represents the most significant clinical, social, and financial burden of any human illness. Despite recent progresses in cancer diagnosis and management, traditional cancer chemotherapies have shown several adverse side effects and loss of potency due to increased resistance. As a result, one of the current approaches is on with the search of bioactive anticancer compounds from natural sources. Neopeltolide is a marine-derived macrolide isolated from deep-water sponges collected off Jamaica's north coast. Its mechanism of action is still under research but represents a potentially promising novel drug for cancer therapy. In this review, we first illustrate the general structural characterization of neopeltolide, the semi-synthetic derivatives, and current medical applications. In addition, we reviewed its anticancer properties, primarily based on in vitro studies, and the possible clinical trials. Finally, we summarize the recent progress in the mechanism of antitumor action of neopeltolide. According to the information presented, we identified two principal challenges in the research, i) the effective dose which acts neopeltolide as an anticancer compound, and ii) to unequivocally establish the mechanism of action by which the compound exerts its antiproliferative effect.

Solid Lipid Nanoparticles: An Approach to Improve Oral Drug Delivery.

Nanoparticles have shown overall beneficial effects in drug administration. Specifically, solid lipid nanoparticles (SLN) have emerged as an alternative to polymer-based systems. However, the oral administration of SLN, the first choice for conventional medications, has not been addressed due to the taboo surrounding the complicated transit that this delivery route entails. This review focuses on the encapsulation of drugs into SLN as a strategy for improving oral administration. Examples of applications of SLN to enhance the absorption and bioavailability of poorly-soluble drugs and protect acid-labile active molecules are discussed. This work also emphasizes the importance of developing SLN-based systems to treat health issues such as neurological diseases and cancer, and combat antibiotic resistance, three significant and increasingly common current public health problems. The review sections clarify how SLN can improve bioavailability, target therapeutic agents, and reduce side effects.

Light stimulation during postnatal development is not determinant for glutamatergic neurotransmission from the retinohypothalamic tract to the suprachiasmatic nucleus in rats.

The hypothalamic suprachiasmatic nucleus (SCN) is the leading circadian pacemaker in mammals, which synchronizes with environmental light through the retinohypothalamic tract (RHT). Although the SCN regulates circadian rhythms before birth, postnatal synaptic changes are needed for the RHT-SCN pathway to achieve total functional development. However, it is unknown whether visual experience affects developmental maturation. Here, we studied the effects of constant darkness (DD) rearing on the physiology (at pre- and postsynaptic levels) of glutamatergic neurotransmission between RHT and SCN during postnatal development in rats. Upon recording spontaneous and evoked excitatory postsynaptic currents (EPSCs) by electrical stimulation of RHT fibers, we found that DD animals at early postnatal ages (P3-19) exhibited different frequencies of spontaneous EPSCs and lower synaptic performance (short-term depression, release sites, and recruitment of RHT fibers) when compared with their normal light/dark (LD) counterparts. At the oldest age evaluated (P30-35), there was a synaptic response strengthening (probability of release, vesicular re-filling rate, and reduced synaptic depression) in DD rats, which functionally equaled (or surmounted) that of LD animals. Control experiments evaluating EPSCs in ventral SCN neurons of LD rats during day and night revealed no significant differences in spontaneous or evoked EPSCs by high-frequency trains in the RHT at any postnatal age. Our results suggest that DD conditions induce a compensatory mechanism in the glutamatergic signaling of the circadian system to increase the chances of synchronization to light at adult ages, and that the synaptic properties of RHT terminals during postnatal development are not critically influenced by environmental light.

Preparation of Co-Processed Excipients for Controlled-Release of Drugs Assembled with Solid Lipid Nanoparticles and Direct Compression Materials.

The purpose of the study was to develop a novel, directly compressible, co-processed excipient capable of providing a controlled-release drug system for the pharmaceutical industry. A co-processed powder was formed by adsorption of solid lipid nanoparticles (SLN) as a controlled-release film onto a functional excipient, in this case, dicalcium phosphate dihydrate (DPD), for direct compression (Di-Tab®). The co-processed excipient has advantages: easy to implement; solvent-free; industrial scaling-up; good rheological and compressibility properties; and the capability to form an inert platform. Six different batches of Di-Tab®:SLN weight ratios were prepared (4:0.6, 3:0.6, 2:0.6, 1:0.6, 0.5:0.6, and 0.25:0.6). BCS class III ranitidine hydrochloride was selected as a drug model to evaluate the mixture's controlled-release capabilities. The co-processed excipients were characterized in terms of powder rheology and dissolution rate. The best Di-Tab®:SLN ratio proved to be 2:0.6, as it showed high functionality with good flow and compressibility properties (Carr Index = 16 ± 1, Hausner Index = 1.19 ± 0.04). This ratio could control release for up to 8 h, so it fits the ideal profile calculated based on biopharmaceutical data. The compressed systems obtained using this powder mixture behave as a matrix platform in which Fickian diffusion governs the release. The Higuchi model can explain their behavior.

Implementation of the emulsification-diffusion method by solvent displacement for polystyrene nanoparticles prepared from recycled material.

From an integral perspective, nanotechnology can be used to care for the environment by improving current preparation methods and facilitating industrial scale-up. This article discusses the implementation of techniques for obtaining polystyrene nanoparticles (PSN), as an added value, using an emulsification and solvent displacement method (EDSD); the solvent displacement is a novel modification to the emulsion-diffusion methodology, where the diffusion is done directly on the emulsion, which allows concentrated dispersions that facilitate direct use to be obtained, eliminating the dilution with water and the recovery of water by additional processes. The solvent was recovered by reduced pressure, which is class 3, conforming to ICH, and making this method sustainable. The optimization of this process has not been reported elsewhere. This approach made it possible to obtain highly-concentrated nanoparticles while allowing the reuse of the solvent. A scaling proposal is presented that integrates the conditioning of the solid urban waste material called expanded polystyrene (EPS) foam that constitutes a serious environmental problem both nationally and globally. Hence, the article presents an alternative to the recycling of EPS, and a methodology in the context of green chemistry, because solvent is recovered to prepare other batches. The PSN obtained from this waste material had a minimum particle size of 225.8 nm, with a polydispersion index of 0.158. Process performance was 97.1%, and the solvent was recovered at a maximum rate of 85%. The morphology of the PSN was spherical and uniform, with a smooth surface.

Synthesis and drug loading improvements on mesoporous SBA-15 by spray drying.

SBA-15 mesoporous silica is a material used as drug carrier material due to its structural characteristics and biocompatibility. The large surface area of this material improves drug loading and drug release. Typically, SBA-15 is produced by a cooperative self-assembly process under acidic conditions using the triblock copolymers as template and tetraethoxysilane (TEOS) as the silica sources under conventional and batched process. In the last years, spray drying has been proposed to reduce the time to obtain SBA-15 (dry and not calcined) to just seconds, whereas with conventional techniques, this process can take from 6 to 48 h. Additionally, the loading, dissolution, and stability of drugs are improved using co-spray drying (SBA-15 and drugs) due to the pore spatial confinement and avoiding the re-crystallization process of drugs. Furthermore, drug-loaded SBA-15 particles obtained by spray drying have a defined size, high sphericity, and easy handling these characteristics are relevant to its incorporation in dosage forms. Several factors influence the final characteristics of SBA-15 drug-loaded particles, for mention a few: precursors, solvents, time of aging, the temperature of drying, pressure, etc. In this review, the key parameters for the synthesis and loading of drugs on SBA-15 using the spray drying technique are explored and analyzed giving information about how these parameters impact the loading, dissolution, and stability of drugs.

Hyaluronic acid in wound dressings.

Human skin possesses an essential function in the maintenance of individuals' health. However, it may undergo a variety of lesions that produce wounds of distinct severity. In this respect, instantly after any skin wound, the process of tissue regeneration and repair initiates. Nevertheless, diverse factors can delay this process, including bacterial infections, nutritional status, age, hypoxia, chronic diseases, necrosis, and vascular and arterial diseases. Thus, wound dressings are frequently used to improve wound healing. Those wound dressings are fabricated with diverse materials, which confer them different properties. In this regard, hyaluronic acid is a natural polysaccharide widely distributed in extracellular matrices of mammal tissues, which possesses remarkable attributes in terms of biocompatibility, biodegradability, and low cost. Moreover, hyaluronic acid exhibits several beneficial effects on wound healing, such as the decrease of inflammatory processes, regulation of tissue remodeling, and enhancement of angiogenesis. Therefore, in recent years, there is growing attention in this polysaccharide for the design and manufacture of novel wound dressings, which have shown encouraging properties. Here, we describe the different approaches of hyaluronic acid for the production of wound dressings, encompassing hydrogels, films, scaffolds, foams, topical formulations, and nanoformulations, as well as its beneficial effects on wound healing. Finally, we discuss perspectives about the use of hyaluronic acid in wound dressings.

Xanthan gum in drug release.

Controlled release is of vital relevance for many drugs; thus, there is a keen interest in materials that can improve the release profiles of formulations administered via buccal, transdermal, ophthalmic, vaginal, and nasal. The desirable effects of those materials include the improvement of stability, adhesiveness, solubility, and retention time. Hence, different synthetic and natural polymers are utilized to achieve these objectives. In this respect, xanthan gum is an anionic polysaccharide that can be obtained from Xanthomonas bacteria. It is a natural polymer broadly employed in numerous food products, lotions, shampoos, and dermatological articles. Furthermore, due to its physicochemical features, xanthan gum is growingly utilized for the development and improvement of drug delivery systems. In this regard, encouraging findings have been revealed by recent formulations for pharmaceutical applications, including antiviral carriers, antibacterial transporters, transdermal patches, vaginal formulations, and anticancer medications. In this article, we perform a concise description of the chemical properties of xanthan gum and its role as a modifier of drug release. Furthermore, we present an outlook of the state of the art of research focused on the utilization of xanthan gum in varied pharmaceutical formulations, which include tablets, films, hydrogels, and nanoformulations. Finally, we discuss some perspectives about the use of xanthan gum in these formulations.

Synergistic antidepressant-like effect of capsaicin and citalopram reduces the side effects of citalopram on anxiety and working memory in rats.

RATIONALE: We have previously shown that in rats, capsaicin (Cap) has antidepressant-like properties when assessed using the forced swimming test (FST) and that a sub-threshold dose of amitriptyline potentiates the effects of Cap. However, synergistic antidepressant-like effects of the joint administration of Cap and the selective serotonin reuptake inhibitor citalopram (Cit) have not been reported. OBJECTIVES: To assess whether combined administration of Cap and Cit has synergistic effects in the FST and to determine whether this combination prevents the side effects of Cit. METHODS: Cap, Cit, and the co-administration of both substances were evaluated in a modified version of the FST (30-cm water depth) conducted in rats, as well as in the open field test (OFT), elevated plus maze (EPM), and Morris water maze (MWM). RESULTS: In line with previous studies, independent administration of Cap and Cit displayed antidepressant-like properties in the FST, while the combined injection had synergistic effects. In the OFT, neither treatment caused significant increments in locomotion. In the EPM, the time spent in the closed arms was lower in groups administered either only Cap or a combination of Cap and Cit than in groups treated with Cit alone. In the MWM, both Cap and the joint treatment (Cap and Cit) improved the working memory of rats in comparison with animals treated only with Cit. CONCLUSION: Combined administration of Cap and Cit produces a synergistic antidepressant-like effect in the FST and reduces the detrimental effects of Cit on anxiety and working memory.

Recent Advances in Elastin-Based Biomaterial.

Elastin is one of the main components of the extracellular matrix; it provides resistance and elasticity to a variety of tissues and organs of the human body, besides participating in cellular signaling. On the other hand, elastin-derived peptides are synthetic biopolymers with a similar conformation and structure to elastin, but these possess the advantage of solubility in aqueous mediums. Due to their biological activities and physicochemical properties, elastin and related peptides may be applied as biomaterials to develop diverse biomedical devices, including scaffolds, hydrogels, and drug delivery systems for tissue engineering. Likewise, the combination of elastin with natural or synthetic polymers has demonstrated to improve the mechanical properties of biomedical products and drug delivery systems. Here we comprehensively describe the physicochemical properties and physiological functions of elastin. Moreover, we offer an overview of the use of elastin and its derivative polymers as biomaterials to develop scaffolds and hydrogels for tissue engineering. Finally, we discuss some perspectives on the employment of these biopolymers to fabricate new biomedical products.

Modifications in Vaginal Microbiota and Their Influence on Drug Release: Challenges and Opportunities.

Vaginal drug delivery represents an attractive alternative to achieve local and systemic effects due to the high contact surface exposed, the mucoadhesion of the epithelium, and the high innervation that facilitates the absorption of drugs into the bloodstream. However, despite the confinement of the vaginal cavity, it is an organ with a highly variable microenvironment. Mechanical alterations such as coitus, or chemical changes such as pH and viscosity, modify the release of drugs. In addition, changes in vaginal microbiota can influence the entire vaginal microenvironment, thus determining the disposition of drugs in the vaginal cavity and decreasing their therapeutic efficacy. Therefore, the influence of microorganisms on vaginal homeostasis can change the pre-established scenario for the application of drugs. This review aims to provide an explanation of normal vaginal microbiota, the factors that modify it, its involvement in the administration of drugs, and new proposals for the design of novel pharmaceutical dosage forms. Finally, challenges and opportunities directed toward the conception of new effective formulations are discussed.

Formulations of Curcumin Nanoparticles for Brain Diseases.

Curcumin is a polyphenol that is obtained from Curcuma longa and used in various areas, such as food and textiles. Curcumin has important anti-inflammatory and antioxidant properties that allow it to be applied as treatment for several emerging pathologies. Remarkably, there are an elevated number of publications deriving from the terms "curcumin" and "curcumin brain diseases", which highlights the increasing impact of this polyphenol and the high number of study groups investigating their therapeutic actions. However, its lack of solubility in aqueous media, as well as its poor bioavailability in biological systems, represent limiting factors for its successful application. In this review article, the analysis of its chemical composition and the pivotal mechanisms for brain applications are addressed in a global manner. Furthermore, we emphasize the use of nanoparticles with curcumin and the benefits that have been reached as an example of the extensive advances in this area of health.

Comprehensive mapping of human body skin hydration: A pilot study.

BACKGROUND: Previous studies analyzed a series of representative anatomical regions in the human body; however, there is a wide structural and cellular variability in the constitution of the skin. Our objective was to perform a comprehensive assessment of human skin hydration throughout the largest possible area. MATERIALS AND METHODS: Hydration was registered by Corneometer® CM825 probe in 23 anatomical regions of five healthy men. Each zone was analyzed by 2-cm segments in the supine, prone, and lateral positions. A total of 7863 measurements were registered. RESULTS: Differences in the degree of hydration among the prone, supine, and lateral regions were observed. The chest and back showed a pattern of increased hydration toward the neck area. Higher levels of hydration were evidenced in the proximal areas and in the regions near the elbow and knee. The regions of greater mechanical wear and with greater exposure to the sun exhibited a lower degree of hydration. CONCLUSION: The human skin exhibited hydration patterns influenced by anatomical function and the degree of sun exposure. Detailed information of the hydration patterns could serve as reference for the design of topical products, as an indicator of their effectiveness, and for the monitoring of skin pathologies.

Approaches in Polymeric Nanoparticles for Vaginal Drug Delivery: A Review of the State of the Art.

The vagina is a region of administration with a high contact surface to obtain local or systemic effects. This anatomical area represents special interest for government health systems for different sexually transmitted infections. However, the chemical changes of the vagina, as well as its abundant mucus in continuous exchange, act as a barrier and a challenge for the development of new drugs. For these purposes, the development of new pharmaceutical forms based on nanoparticles has been shown to offer various advantages, such as bioadhesion, easy penetration of the mucosa, and controlled release, in addition to decreasing the adverse effects of conventional pharmaceutical forms. In order to obtain nanoparticles for vaginal administration, the use of polymers of natural and synthetic origin including biodegradable and non-biodegradable systems have gained great interest both in nanospheres and in nanocapsules. The main aim of this review is to provide an overview of the development of nanotechnology for vaginal drug release, analyzing the different compositions of polymeric nanoparticles, and emphasizing new trends in each of the sections presented. At the end of this review, a section analyzes the properties of the vehicles employed for the administration of nanoparticles and discusses how to take advantage of the properties that they offer. This review aims to be a reference guide for new formulators interested in the vaginal route.

Nanosystems in Edible Coatings: A Novel Strategy for Food Preservation.

Currently, nanotechnology represents an important tool and an efficient option for extending the shelf life of foods. Reducing particle size to nanometric scale gives materials distinct and improved properties compared to larger systems. For food applications, this technology allows the incorporation of hydrophilic and lipophilic substances with antimicrobial and antioxidant properties that can be released during storage periods to increase the shelf life of diverse products, including whole and fresh-cut fruits and vegetables, nuts, seeds, and cheese, among others. Edible coatings are usually prepared with natural polymers that are non-toxic, economical, and readily available. Nanosystems, in contrast, may also be prepared with biodegradable synthetic polymers, and liquid and solid lipids at room temperature. In this review, recent developments in the use of such nanosystems as nanoparticles, nanotubes, nanocomposites, and nanoemulsions, are discussed critically. The use of polymers as the support matrix for nanodispersions to form edible coatings for food preservation is also analyzed, but the central purpose of the article is to describe available information on nanosystems and their use in different food substrates to help formulators in their work.

Controlled-release biodegradable nanoparticles: From preparation to vaginal applications.

This study aimed to prepare poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with chitosan (CTS) surface modification to be used as a vaginal delivery system for antimycotic drugs. Clotrimazole was encapsulated with entrapment efficiencies of 86.1 and 68.9% into Clotrimazole-PLGA-NPs (CLT-PLGA-NPs) and PLGA-NPs with CTS-modified surface (CLT-PLGA-CTS-NPs), respectively. The later NPs exhibited a larger size and higher positive zeta potential (Z potential) in comparison to unmodified NPs. In vitro release kinetic studies indicated that Clotrimazole was released in percentages of >98% from both nanoparticulate systems after 18days. Antifungal activity and mucoadhesive properties of NPs were enhanced when CTS was added onto the surface. In summary, these results suggested that Clotrimazole loaded into PLGA-CTS-NPs has great potential for vaginal applications in treating vaginal infections generated by Candida albicans.

Nanotechnology As Potential Tool for siRNA Delivery in Parkinson's Disease.

BACKGROUND: The lack of an outright treatment for Parkinson's disease (PD) is a pivotal concern in medicine and has driven the search for novel alternatives for treating the disease. Among the proposed approaches, small interfering RNA (siRNA)-based therapy is attracting significant attention as a potential method for the treatment of PD; however, siRNAs delivery possesses potential drawbacks, such as reduced stability in blood circulation and low capacity for reaching the target site. OBJECTIVE: This review aims to explore siRNA-based approaches to PD and the latest advances for designing nanoparticles that effectively target siRNAs to the action site and that protect these against degradation in blood circulation. RESULTS: siRNA-based approaches provide an interesting option for designing new strategies for treating PD through the silencing of genes, whose abnormal expressions contribute to the pathophysiology of the disease; however, siRNA delivery to the brain is a key issue that remains unsolved to date. Current research efforts are focused on designing vectors that effectively transport and protect siRNAs. In this regard, nanoparticles are being developed as carriers for siRNAs with controlled delivery efficiency and low toxicity profiles, and these represent an alternative to common vectors. CONCLUSION: Identification of putative gene targets for siRNA therapy of PD has set the pace for researching non-viral vectors; however, the technological aspects for tackling the challenge that siRNAs targeting to the brain represents are essentials. In this respect, the formulation of siRNAs in nanoparticles would avoid harmful side effects, such as immunogenic and oncogenic drawbacks.

Feasibility of obtaining in situ nanocapsules through modified self-microemulsifying drug delivery systems. A new manufacturing approach for oral route administration.

Nanocapsules (NCs) are submicron-sized core shell systems which present important advantages such as improvement of drug efficacy and bioavailability, prevention of drug degradation, and provision of controlled-release delivery. The available methods for NC production require expensive recovery and purification steps which compromised the morphology of NCs. Industrial applications of NCs have been avoided due to the aforementioned issues. In this study, we developed a new method based on a modified self-microemulsifying drug delivery system (SMEDDS) for in situ NCs production within the gastrointestinal tract. This new methodology does not require purification and recovery steps and can preserve the morphology and the functionality of NCs. The in situ formed NCs of Eudragit® RL PO were compared with nanospheres (NEs) in order to obtain evidence of their core-shell structure. NCs presented a spherical morphology with a size of 126.2 ± 13.1 nm, an ibuprofen encapsulation efficiency of 31.3% and a zeta-potential of 37.4 mV. Additionally, NC density and release profile (zero order) showed physical evidence of the feasibility of NCs in situ creation.