The Development and Pre-Clinical Anti-Inflammatory Efficacy of a New Transdermal Ureasil-Polyether Hybrid Matrix Loaded with Flavonoid-Rich Annona muricata Leaf Extract.

This study aimed to develop a novel ureasil-polyether transdermal hybrid matrix (U-PEO) loaded with Annona muricata concentrated extract (AMCE), which exhibits potent anti-inflammatory activity. The extract was obtained by maceration, a method that allowed for the extraction of a high concentration of flavonoids (39.27 mg/g of extract). In vivo tests demonstrated that 10 mg/kg of AMCE inhibited inflammation for 6 h. The physicochemical characterization of U-PEO with AMCE was conducted via a thermogravimetric analysis (TGA), while its surface was recorded using atomic force microscopy (AFM). The in vitro macroscopic swelling and release tests demonstrated the hydrophilic profile of the material and the percentage of AMCE released. The TGA results demonstrated that the system exhibited physical compatibility due to the thermal stability of U-PEO. Additionally, the AFM analysis revealed a rough and porous surface, with a particular emphasis on the system with AMCE. The release resulted in the liberation of 23.72% of AMCE within 24 h. Finally, the preclinical tests demonstrated that U-PEO with AMCE was also capable of effectively inhibiting inflammation for 6 h, a duration comparable to that of a commercial formulation. The results permit the advancement of the study towards the development of a transdermal system, thereby rendering its application in clinical studies feasible.

Cellulose Acetate Microparticles Synthesized from Agave sisalana Perrine for Controlled Release of Simvastatin.

Simvastatin (SIM) is widely prescribed to treat hyperlipidemia, despite its limitations, such as a short half-life and low oral bioavailability. To overcome these drawbacks, the development of a controlled-release formulation is desirable. This study aims to develop a microparticulate system based on cellulose acetate (ACT) obtained from Agave sisalana Perrine to promote a controlled SIM release. SIM-loaded microparticles (SMP) were prepared using the solvent emulsification-evaporation method. Several parameters were evaluated, including particle size, surface charge, morphology, encapsulation efficiency, thermochemical characteristics, crystallinity, and in vitro release profile. ACT exhibited favorable flow properties after acetylation, with a degree of substitution values superior to 2.5, as confirmed by both the chemical route and H-NMR, indicating the formation of cellulose triacetate. The obtained SMP were spherical with an average size ranging from 1842 to 1857 nm, a zeta potential of -4.45 mV, and a high SIM incorporation efficiency (98%). Thermal and XRD analyses revealed that SIM was homogeneously dispersed into the polymeric matrix in its amorphous state. In vitro studies using dialysis bags revealed that the controlled SIM release from microparticles was higher under simulated intestinal conditions and followed the Higuchi kinetic model. Our results suggest that ACT-based microparticles are a promising system for SIM delivery, which can improve its bioavailability, and result in better patient compliance.

The Efficacy of Hybrid Vaginal Ovules for Co-Delivery of Curcumin and Miconazole against Candida albicans.

Curcumin (CUR) is a natural compound that can be combined with miconazole (MCZ) to improve vulvovaginal candidiasis (VVC) caused by Candida albicans treatment's efficacy. This study aimed to develop ureasil-polyether (U-PEO) vaginal ovules loaded with CUR and MCZ for the treatment of VVC. Physicochemical characterization was performed by thermogravimetry (TGA), differential thermal analysis (DTA), Fourier transform infrared spectroscopy (FTIR), and in vitro release. Antifungal assays were used to determine minimum inhibitory concentrations (MICs) and synergism between CUR and MCZ, and the activity of U-PEO ovules were performed by microdilution and agar diffusion. TGA results showed high thermal stability of the hybrid ovules. In DTA, the amorphous character of U-PEO and a possible interaction between CUR and MCZ were observed. FTIR showed no chemical incompatibility between the drugs. In vitro release resulted in 80% of CUR and 95% of MCZ released within 144 h. The MICs of CUR and MCZ were 256 and 2.5 µg/mL, respectively. After combining the drugs, the MIC of MCZ decreased four-fold to 0.625 µg/mL, while that of CUR decreased eight-fold to 32 µg/mL. Synergism was confirmed by the fractional inhibitory concentration index (FICI) equal to 0.375. U-PEO alone showed no antifungal activity. U-PEO/MCZ and U-PEO/CUR/MCZ ovules showed the greatest zones of inhibition (≥18 mm). The results highlight the potential of the ovules to be administered at a lower frequency and at reduced doses compared to available formulations.

Potential of Nanomedicines as an Alternative for the Treatment of Colorectal Cancer - A Review.

Colorectal cancer is the third most common cancer and the second in cases of cancer-related death. Polytherapy generates many adverse effects, leading the patient to give up. Nanotechnology has been studied in recent years to circumvent limitations. Groups composed of polymeric, lipid, and inorganic nanoparticles are the most purpose. Thus, the objective of this work is to bring information on how nanosystems can improve the chemotherapeutic treatment for colorectal cancer. Therefore, a search in journals such as "LILACS", "SciELO" and "PubMed/Medline" was performed, resulting in 25,000 articles found when applied the search engines "nanoparticle," "colorectal cancer," "malignant neoplasms," and "chemotherapy." After inclusion and exclusion factors, 24 articles remained, which were used as the basis for this integrative review. The results reveal that, regardless of the choice of matrix, nanoparticles showed an increase in bioavailability of the active, increasing the half-life by up to 13 times, modified release, as well as a significant reduction in tumor size, with cell viability up to 20% lower than the free drug tested, in different colorectal cancer cell lines, such as HCT-116, HT-29, and CaCo-2. However, more in vivo and clinical studies need to be performed, regardless of the formulation of its matrix, aiming at a higher rate of safety for patients and stability of the formulations, as well as knowledge of detailed indices of its pharmacokinetics and pharmacodynamics, seeking to avoid further damage to the recipient organism.

Enhancing Antifungal Treatment of Candida albicans with Hypericin-Loaded Nanostructured Lipid Carriers in Hydrogels: Characterization, In Vitro, and In Vivo Photodynamic Evaluation.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a worldwide public health problem caused predominantly by the opportunistic polymorphic fungus Candida albicans, whose pathogenicity is associated with its morphological adaptability. To potentiate the treatment of C. albicans-induced VVC by an alternative method as photodynamic therapy (PDT), hypericin (Hy), a potent photosensitizer compound was incorporated into a nanostructured lipid carrier (NLC) and dispersed in hydrogel (HG). METHODS: After preparation of the sonication process, an NLC loaded with Hy was dispersed in HG based on Poloxamer 407 and chitosan obtaining Hy.NLC-HG. This hydrogel system was physically and chemically characterized and its in vitro and in vivo photodynamic and antifungal effects were evaluated. RESULTS: Through scanning electron microscopy, it was possible to observe a hydrogel system with a porous polymeric matrix and irregular microcavities. The Hy.NLC-HG system showed mucoadhesive properties (0.45 ± 0.08 N) and a satisfactory injectability (15.74 ± 4.75 N.mm), which indicates that it can be easily applied in the vaginal canal, in addition to a controlled and sustained Hy release profile from the NLC-HG of 28.55 ± 0.15% after 720 min. The in vitro antibiofilm assay significantly reduced the viability of C. albicans (p < 0.001) by 1.2 log10 for Hy.NLC-HG/PDT and 1.9 log10 for PS/PDT, Hy.NLC/PDT, and free RB/PDT, compared to the PBS/PDT negative control. The in vivo antifungal evaluation showed that animals treated with the vaginal cream (non-PDT) and the PDT-mediated Hy.NLC-HG system showed a significant difference of p < 0.001 in the number of C. albicans colonies (log) in the vaginal canal, compared to the inoculation control group. CONCLUSIONS: Thus, we demonstrate the pharmaceutical, antifungal, and photodynamic potential of hydrogel systems for Hy vaginal administration.

Hybrid Membranes of the Ureasil-Polyether Containing Glucose for Future Application in Bone Regeneration.

The application of mesenchymal stem cells (MSC) in bone tissue regeneration can have unpredictable results due to the low survival of cells in the process since the lack of oxygen and nutrients promotes metabolic stress. Therefore, in this work, polymeric membranes formed by organic-inorganic hybrid materials called ureasil-polyether for modified glucose release were developed in order to overcome the problems posed by a of lack of this nutrient. Thus, membranes formed by polymeric blend of polypropylene oxide (PPO4000) and polyethylene oxide (PEO500) with 6% glucose incorporation were developed. Physical-chemical characterization techniques were performed, as well as tests that evaluated thermal properties, bioactivity, swelling, and release in SBF solution. The results of the swelling test showed an increase in membrane mass correlated with an increase in the concentration of ureasil-PEO500 in the polymeric blends. The membranes showed adequate resistance when subjected to the application of a high compression force (15 N). X-ray diffraction (XRD) evidenced peaks corresponding to orthorhombic crystalline organization, but the absence of glucose-related peaks showed characteristics of the amorphous regions of hybrid materials, likely due to solubilization. Thermogravimetry (TG) and differential scanning calorimetry (DSC) analyses showed that the thermal events attributed to glucose and hybrid materials were similar to that seen in the literature, however when glucose was incorporated into the PEO500, an increase in rigidity occurs. In PPO400, and in the blends of both materials, there was a slight decrease in Tg values. The smaller contact angle for the ureasil-PEO500 membrane revealed the more hydrophilic character of the material compared to other membranes. The membranes showed bioactivity and hemocompatibility in vitro. The in vitro release test revealed that it is possible to control the release rate of glucose and the kinetic analysis revealed a release mechanism characteristic of anomalous transport kinetics. Thus, we can conclude that ureasil-polyether membranes have great potential to be used as a glucose release system, and their future application has the potential to optimize the bone regeneration process.

Polyvinyl Alcohol Nanofibers Blends as Drug Delivery System in Tissue Regeneration.

Nanofibers have shown promising clinical results in the process of tissue regeneration since they provide a similar structure to the extracellular matrix of different tissues, high surface-to-volume ratio and porosity, flexibility, and gas permeation, offering topographical features that stimulate cell adhesion and proliferation. Electrospinning is one of the most used techniques for manufacturing nanomaterials due to its simplicity and low cost. In this review, we highlight the use of nanofibers produced with polyvinyl alcohol and polymeric associations (PVA/blends) as a matrix for release capable of modifying the pharmacokinetic profile of different active ingredients in the regeneration of connective, epithelial, muscular, and nervous tissues. Articles were selected by three independent reviewers by analyzing the databases, such as Web of Science, PubMed, Science Direct, and Google Scholar (last 10 years). Descriptors used were "nanofibers", "poly (vinyl alcohol)", "muscle tissue", "connective tissue", "epithelial tissue", and "neural tissue engineering". The guiding question was: How do different compositions of polyvinyl alcohol polymeric nanofibers modify the pharmacokinetics of active ingredients in different tissue regeneration processes? The results demonstrated the versatility of the production of PVA nanofibers by solution blow technique with different actives (lipo/hydrophilic) and with pore sizes varying between 60 and 450 nm depending on the polymers used in the mixture, which influences the drug release that can be controlled for hours or days. The tissue regeneration showed better cellular organization and greater cell proliferation compared to the treatment with the control group, regardless of the tissue analyzed. We highlight that, among all blends, the combinations PVA/PCL and PVA/CS showed good compatibility and slow degradation, indicating their use in prolonged times of biodegradation, thus benefiting tissue regeneration in bone and cartilage connective tissues, acting as a physical barrier that results in guided regeneration, and preventing the invasion of cells from other tissues with increased proliferation rate.

Physicochemical Characterization of Silver Sulfadiazine in Polymeric Wound Dressings.

The insertion of topical antimicrobials in wound treatment represented an important role in patient management. Among these agents, silver sulfadiazine (AgSD), introduced in the therapy of wounds and burns in the 1960s, is considered the gold standard in treatment due to its mechanism of action, in addition to its proven efficacy and safety. The association of AgSD with polymers for the development of curative formulations has been reported. The evaluation of the physical-chemical properties of these systems with the aid of analytical techniques of characterization is essential for the determination of their activities, besides allowing the detection of possible incompatibilities between AgSD and polymers. Thus, this review presents the main techniques of physicochemical characterization used in the evaluation of systems containing AgSD with curative purposes in order to provide parameters to ensure the efficacy and safety of these new therapeutic options. Microscopic, thermoanalytical, and spectroscopic techniques, for example, provide information on system properties such as surface chemical composition, crystallinity, morphology, and thermal stability of curative formulations containing AgSD. These techniques are important in the selection of the most appropriate techniques during the development of a polymeric curative system containing AgSD, in addition to providing information for cost reduction of a possible scale-up and the establishment of methodologies for quality control of these systems to ensure their efficacy and safety.

Antimicrobial photodynamic therapy mediated by methylene blue-loaded polymeric micelles against Streptococcus mutans and Candida albicans biofilms.

BACKGROUND: Streptococcus mutans and Candida albicans can colonize the teeth, the oral cavity as biofilm and can cause oral infections. Thus, strategies to prevent and control oral biofilms are requested. The present study aims the development and characterization of methylene blue (MB)-loaded polymeric micelles for antimicrobial photodynamic therapy (aPDT) against Streptococcus mutans and Candida albicans biofilms METHODS: MB-loaded polymeric micelles were produced and characterized by particle size, polydispersity index, morphology, zeta potential, stability, MB release profile, and antimicrobial effect against S. mutans and C. albicans biofilms. RESULTS: MB-loaded polymeric micelles showed a reduced particle size, moderate polydisperse profile, spherical and neutral shape, which demonstrated to be promising features to allow micelles penetration into biofilms. Antimicrobial effect against bacterial and yeast biofilms was demonstrated once MB was irradiated by light under 660 nm (aPDT). Furthermore, MB-loaded polymeric micelles showed significant inhibition of S. mutans and C. albicans biofilms. Furthermore, the treatment with MB-micelles incubated with high pre-incubation times (15 and 30 min) were more effective than 5 min. It can be explained by the time required for this nanosystem to penetrate the innermost layer of biofilms and release MB for aPDT. CONCLUSION: MB-loaded polymeric micelles can effectively decrease the bacteria and yeast viability and it may cause positive impacts in the clinical practice. Thus, the developed formulation showed potential in the treatment to remove oral biofilms, but clinical studies are needed to confirm its potential.

Photodynamic potential of hexadecafluoro zinc phthalocyanine in nanostructured lipid carriers: physicochemical characterization, drug delivery and antimicrobial effect against Candida albicans.

This study aims to develop and characterize NCL loaded with ZnF16Pc (Pc) for application in antimicrobial photodynamic therapy. For the development of the NLC, the fusion-emulsification technique followed by sonication was applied. NLC and Pc-NLC were characterized in terms of mean diameter (Dm.n), polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency (%EE), transmission electron microscopy (TEM), differential scanning (DSC), photobleaching and singlet oxygen generation in cellular systems (SOSG), and in vitro release assays performed by the beaker method, using dialysis membranes. Cell viability was performed by colony forming units (CFU/mL). The mean size of NLC and Pc-NLC was 158 nm ± 1.49 to 161.80 nm and showed PdI < 0.3 and ZP between -17.8 and -19.9, and stable during storage time (90 days). The TEM presented spherical particles, the Pc-NLC promoted the encapsulation of 75.57% ± 0.58. DSC analysis confirmed that there was no incompatibility between Pc and NLC. The analysis of the photodegradation profile proved to be photostable after encapsulation and this corroborates the data obtained by SOSG. In vitro release showed controlled and prolonged release. PDT Pc-NLC exhibited greater antifungal effect against C. albicans (3 log10 reduction) than Pc-NLC without light (1 log10 reduction). NLC can be an alternative to the application of Pc and improve the effect during PDT treatment.

Dexamethasone-Loaded Ureasil Hydrophobic Membrane for Bone Guided Regeneration.

Physical barrier membranes have been used to release active substances to treat critical bone defects; however, hydrophilic membranes do not present a prolonged release capacity. In this sense, hydrophobic membranes have been tested. Thus, this study aimed to develop hydrophobic membranes based on mixtures of ureasil-polyether-type materials containing incorporated dexamethasone (DMA) for the application in guided bone regeneration. The physicochemical characterization and biological assays were carried out using small-angle X-ray scattering (SAXS), an in vitro DMA release study, atomic force microscopy (AFM), a hemolysis test, and in vivo bone formation. The swelling degree, SAXS, and release results revealed that the u-PPO400/2000 membrane in the proportion of 70:30 showed swelling (4.69% ± 0.22) similar to the proportions 90:10 and 80:20, and lower than the proportion 60:40 (6.38% ± 0.49); however, an equal release percentage after 134 h was observed between the proportions 70:30 and 60:40. All u-PPO materials presented hemocompatibility (hemolysis ≤2.8%). AFM results showed that the treatments with or without DMA did not present significant differences, revealing a flat/smooth surface, with no pores and/or crystalline precipitates. Finally, in vivo results revealed that for both the commercial hydrophilic membrane and u-PPO400/2000 (70:30) after 60 days, the bone formation volume was 21%. In conclusion, hybrid membranes present unique characteristics for treating critical bone defects, considering the delayed and prolonged release results associated with the physical barrier capacity.

Potential Application of Cephalosporins Carried in Organic or Inorganic Nanosystems against Gram-Negative Pathogens.

Cephalosporins are ß-lactam antibiotics, classified into five generations and extensively used in clinical practice against infections caused by Gram-negative pathogens, including Enterobacteriaceae and P. aeruginosa. Commercially, conventional pharmaceutical forms require high doses to ensure clinical efficacy. Additionally, ß-lactam resistance mechanisms, such as the production of enzymes (called extended-spectrum ß-lactamases) and the low plasma half-life of these antibiotics, have been challenging in clinical therapy based on the use of cephalosporins. In this context, its incorporation into nanoparticles, whether organic or inorganic, is an alternative to temporally and spatially control the drug release and improve its pharmacokinetic and pharmacodynamic limitations. Considering this, the present review unites the cephalosporins encapsulated into organic and inorganic nanoparticles against resistant and nonresistant enterobacteria. We divide cephalosporin generation into subtopics in which we discuss all molecules approved by regulatory agencies. In addition, changes in the side chains at positions R1 and R2 of the central structure of cephalosporins for all semisynthetic derivatives developed were discussed and presented, as the changes in these groups are related to modifications in pharmacological and pharmacokinetic properties, respectively. Ultimately, we exhibit the advances and differences in the release profile and in vitro activity of cephalosporins incorporated in different nanoparticles.

N-acylhydrazone Derivative-Loaded Cellulose Acetate Films: Thermoanalytical, Spectroscopic, Mechanical and Morphological Characterization.

Cellulose acetate (ACT) is one of the most important cellulose derivatives due to its biodegradability and low toxicity, presenting itself as one of the main substitutes for synthetic materials in the development of wound dressing films. The incorporation of a N-acylhydrazonic derivative (JR19), with its promising anti-inflammatory activity, may represent an alternative for the treatment of skin wounds. This work aims to develop and to physicochemically and mechanically characterize ACT films containing JR19. The films were prepared using the 'casting' method and further characterized by thermoanalytical and spectroscopic techniques. In addition, mechanical tests and morphological analysis were performed. Thermogravimetry (TG) and differential scanning calorimetry (DSC) analyses showed that the thermal events attributed to excipients and films were similar, indicating the absence of physical incompatibilities between ACT and JR19. Infrared spectroscopy showed that JR19 was incorporated into ACT films. The characteristic band attributed to C≡N (2279 to 2264 cm-1) was observed in the spectra of JR19, in that of the physical mixture of JR19/ACT, and, to a lesser extent, in the spectra of JR19 incorporated into the ACT film, suggesting some interaction between JR19 and ACT. X-ray diffraction (XRD) evidenced the suppression of the crystallinity of JR19 (diffraction peaks at 8.54°, 12.80°, 14.09°, 16.08°, 18.19°, 22.65°, 23.59°, 24.53°, 25.70°, 28.16° and 30.27°2θ) after incorporation into ACT films. The mechanical tests indicated the adequate integrity of the films and their resistance to bending. The morphological characterization showed JR19 crystals along with a homogeneously distributed porous structure throughout the surface of the films with an average diameter of 21.34 µm and 22.65 µm of the films alone and of those incorporating JR19F, respectively. This study was able to characterize the ACT films incorporating JR19, showing their potential to be further developed as wound healing dressings.

Curcumin-Loaded Micelles Dispersed in Ureasil-Polyether Materials for a Novel Sustained-Release Formulation.

Vulvovaginal candidiasis (VVC) is a vulvar/vaginal infection that affects approximately 75% of women worldwide. The current treatment consists of antimicrobials with hepatotoxic properties and high drug interaction probabilities. Therefore, this study aimed to develop a new treatment to VVC based on micelles containing curcumin (CUR) dispersed in a ureasil-polyether (U-PEO) hybrid. The physical-chemical characterization was carried out in order to observe size, shape, crystallinity degree and particle dispersion in the formulation and was performed by dynamic light scattering (DLS), scanning electron microscopy (SEM), X-ray diffraction (XRD) and through in vitro release study. The results of DLS and SEM exhibited micelles with 35 nm, and encapsulation efficiency (EE) results demonstrated 100% of EE to CUR dispersed in the U-PEO, which was confirmed by the DRX. The release results showed that CUR loaded in U-PEO is 70% released after 10 days, which demonstrates the potential application of this material in different pharmaceutical forms (ovules and rings), and the possibility of multidose based on a single application, suggesting a higher rate of adherence.

In vivo effectiveness of hybrid membranes with osteogenic growth peptide for bone regeneration.

Guided bone regeneration (GBR) technique helps to restore bone tissue through cellular selectivity principle. Currently no osteoinductive membrane exists on the market. Osteogenic growth peptide (OGP) acts as a hematopoietic stimulator. This association could improve the quality of bone formation, benefiting more than 2.2 million patients annually. The objective of this work was to develop membranes from ureasil-polyether materials containing OGP. The membranes were characterized by differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS). OGP was synthesized by the solid phase method. Sterilization results using gamma radiation at 24 kGy did not change the structure of the material, as confirmed by DSC. The SAXS technique revealed the structural homogeneity of the matrix. OGP was incorporated in 66.25 × 10-10  mol and release results showed that the ureasil-PPO400/PEO500 and ureasil-PPO400/PEO1900 membranes released 7% and 21%, respectively, after 48 h. In vivo results demonstrated that the amount and quality of bone tissue formed in the bone defects in the presence of ureasil-polyether membranes with OGP were similar to commercial collagen material with BMP. The results allow us to conclude that membranes with OGP have characteristics that make them potential candidates for the GBR.

Curcumin-loaded Pluronic® F-127 Micelles as a Drug Delivery System for Curcumin-mediated Photodynamic Therapy for Oral Application.

Antimicrobial photodynamic therapy (aPDT) is promising for oral decontamination. Curcumin has been used as photosensitizer; however, the hydrophobic properties can negatively affect aPDT. This study evaluated the aPDT efficacy using Cur-loaded Pluronic® F-127 micelles against Streptococcus mutans and Candida albicans biofilms. Micelles characterization was performed by zeta potential, dynamic light scattering, transmission electron microscopy, absorption and fluorescence spectroscopy. Cur concentrations, cell viability by CFU mL-1 and confocal microscopy were determined. Data were analyzed by parametric and nonparametric tests under 5%. Cur-loaded Pluronic® F-127 exhibited spherical shape, suitable particle size (≤100 nm), adequate polydispersity index, best stability, lower photodegradation and autoaggregation compared to unloaded-Cur. Both microorganisms were sensitive to Cur-loaded Pluronic® F-127 micelles aPDT, with minimum inhibitory concentration (MIC) of 270 µm and 2.1093 µm for S. mutans and C. albicans suspended culture, respectively. Cur-loaded Pluronic® F-127 aPDT exhibited antibacterial/antifungal effect against the biofilms (~3 log10 reduction; P ≤ 0.05); however, similar to unloaded (P ≥ 0.05). Confocal images confirmed these results. Cur-loaded Pluronic® F-127 micelles exhibited good photo-chemical properties and may be a viable alternative to deliver Cur and to improve aPDT effect during the treatment of dental caries. Moreover, Pluronic® micelles can enhance the solubility, stability, permeability and control the release of Cur.

In vivo study of hypericin-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system in a mice model of vulvovaginal candidiasis.

The present study reports the performance of the pigment hypericin (HYP)-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system (LCPS) for the treatment of vulvovaginal candidiasis (VVC) in mice. LCPS composed of 40% of ethoxylated and propoxylated cetyl alcohol, 30% of oleic acid and cholesterol (7:1), 30% of a dispersion of 16% poloxamer 407 and 0.05% of HYP (HYP-LCPS) was prepared and characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and ex vivo permeation and retention studies across vaginal porcine mucosa were performed. In addition, the antifungal properties of the HYP-LCPS were evaluated in a murine in vivo model; for this, infected C57BL female mice groups were treated with both HYP in solution and HYP-LCPS, and after 6 days colony forming unit (CFU)/ml count was performed. PLM and SAXS confirmed that HYP-LCPS is a microemulsion situated in boundary transition region confirming its action as an LCPS. When in contact with simulated vaginal fluid, HYP-LCPS became rigid and exhibited maltase crosses and bragg peaks characteristics of lamellar phase. Ex vivo permeation and retention studies showed that HYP-LCPS provides a localized treatment on the superficial layers of porcine vaginal mucosa. HYP-LCPS induced a significant reduction in the number of CFU/ml in the mice; thus this formulation indicated it is as effective as a commercial dosage form. It was concluded that LCPS maintains the biological activity of HYP and provides an adequate drug delivery system for this lipophilic molecule at the vaginal mucosa, being a promising option in cases of VVC.

Synthesis of ureasil-polyether film forming materials by using environmentally friendly solvent

Organic inorganic hybrids present several advantages as drug release systems, such as: high flexibility, high mechanical and thermal resistance, transparency, and low water solubility. These hybrids are synthesized through a chemical route named sol-gel that usually uses as solvente tetrahydrofuran (THF). Objetives: To develop film formers from hybrid materials replacing THF with ethanol, a less toxic solvent for skin application and for the environment. Methods: Four polymers were used: two based on polyethylene oxide (PEO) with molecular weight of 500 and 1900 g mol-1 and two based on polypropylene oxide (PPO), with molecular weight of 400 and 2000 g mol-1. The structural analysis was performed by FTIR, 1H-NMR and 29Si-NMR, and the thermal-mechanical analysis by DSC and TG-DTA. Results: The results of the thermo-mechanical analysis revealed that the solvent replacement did not affect the thermal stability and flexibility of the di-ureasil hybrid. Conclusions: Structural characterization confirmed the formation of hybrids both in THF and in ethanol. Therefore, ethanol is an excellent solvent for the synthesis of these hybrid matrices, since it allows obtaining the same material without changing its characteristics, with some advantages, however, over THF. Furthermore, this paper describes the efficiency of ethanol as a solvent, which is environmentally friendly, to replace THF in the physical-chemical characteristics of these filming former materials.

A Review of Properties, Delivery Systems and Analytical Methods for the Characterization of Monomeric Glycoprotein Transferrin.

Transferrin is a protein involved in iron uptake by cells and has been identified as a potential target for directing drug-loaded nanoparticles for cancer treatment and diagnosis. Most methods for conjugation of transferrin and nanoparticles involve the formation of a thioeter bond between thiolated transferrin and maleimide-containing nanoparticle. For nanoparticle development, it is important to perform a thorough physicochemical characterization, including quantification of the amount of transferrin functionalizing the delivery system. Thus, following the transferrin and nanoparticle chemical conjugation, an analytical method is need for transferrin quantification. Altogether, we revised both physicochemical and pharmacokinetics transferrin characteristics, the aspects of iron transport after interaction with transferrin, the development of transferrin targeted-nanoparticles, highlighting both their composition, synthesis methods and in vitro/in vivo evaluation. Furthermore, we addressed the analytical methods employed in protein quantification, including spectrophotometric/colorimetric, immunoassays, electrophoretic and chromatographic techniques used to identify and/or quantify of transferrin in biological matrices and drug delivery systems.

Monoclonal Antibodies Carried in Drug Delivery Nanosystems as a Strategy for Cancer Treatment.

Monoclonal antibodies carried in nanosystems have been extensively studied and reported as a promising tool for the treatment of various types of cancers. Monoclonal antibodies have great advantages for the treatment of cancer because their protein structure can bind to the target tissue; however, it has some challenges such as denaturation following heat exposure and extreme values of pH, temperature and solvents, the ability to undergo hydrolysis, oxidation and deamination and the formation of non-native aggregates, which compromise drug stability to a large extent. In addition to these characteristics, they suffer rapid elimination when in the blood, which results in a short half-life and the production of neutralizing antibodies, rendering the doses ineffective. These challenges are overcome with encapsulation in nanosystems (liposomes, polymer nanoparticles, cyclodextrins, solid lipid nanoparticles, nanostructured lipid carriers, dendrimers and micelles) due to the characteristics of improving solubility, permeability, and selectivity only with tumor tissue; with that, there is a decrease in side effects beyond controlled release, which is critical to improving the therapeutic efficacy of cancer treatment. The article was divided into different types of nanosystems, with a description of their definitions and applications in various types of cancers. Therefore, this review summarizes the use of monoclonal antibodies encapsulated in nanosystems and the description of clinical studies with biosimilars. Biosimilars are defined as products that are similar to monoclonal antibodies which are produced when the patent for the monoclonal antibodies expires.