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Graciela Lizeth Pérez-González1,2, Luis Jesús Villarreal-Gómez1,2, Aracely Serrano-Medina,3 Erick José Torres-Martínez1,2, José Manuel Cornejo-Bravo21Escuela de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Unidad Valle de las Palmas, Tijuana, Baja California, México; 2Facultad de Ciencias Químicas e Ingeniería, Universidad Autónoma de Baja California, Calzada Universidad 14418 Parque Industrial Internacional, Tijuana, Baja California 22390, México; 3Facultad de Medicina y Psicología, Universidad Autónoma de Baja California, Unidad Otay, Tijuana, Baja California, MéxicoAbstract: Electrospun nanofibers have been widely studied for many medical applications. They can be designed with specific features, including mucoadhesive properties. This review summarizes the polymeric scaffolds obtained by the electrospinning process that has been applied for drug release in different mucosal sites such as oral, ocular, gastroenteric, vaginal, and nasal. We analyzed the electrospinning parameters that have to be optimized to create reproducible and efficient mucoadhesive nanofibers, among them are: electrical field, polymer concentration, viscosity, flow rate, needle-collector distance, solution conductivity, solvent, environmental parameters, and electrospinning setup. We also revised the mucoadhesive theories as well as the mucoadhesive properties of the polymers used. This review shows that the most studied mucosal site is the oral cavity, because it is accessible and easy to evaluate, while the rest are uncomfortable for the patient and difficult to assess in vivo. We found problems that need to be solved for mucoadhesive electrospun nanofibers, such as improving adhesion strength and mucosal permanence time, and the design of unidirectional release, multilayer systems for the treatment of several pathologies, to ensure the drug concentration in the tissue or target organ.Keywords: mucoadhesives, electrospinning, drug delivery systems, polymers

Pyrocatechol, also known as catechol, is a commonly used compound in various industries; however, it can be toxic when used in high concentrations. Therefore, developing a highly sensitive electrochemical sensor for detecting pyrocatechol is important. Our study utilized a co-precipitation technique to fabricate a nanostructured nickel aluminum layered double hydroxide (Ni-Al-LDH). This material was thoroughly analyzed using advanced techniques to confirm its functionality, crystallinity, and morphology. Subsequently, Ni-Al-LDH was employed as an electrocatalyst for the detection of pyrocatechol in actual samples. The modified electrode showed significant responsiveness to pyrocatechol under specific conditions, with a detection limit of 1 nM. This sensor demonstrated analytical potential for the sensitive determination of pyrocatechol across a range of real samples., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

This study aims to design microgels that are thermo- and pH-sensitive for controlled doxorubicin (Dox) release in response to tumor microenvironment changes. N-isopropylacrylamide (NIPAAm) is widely used for thermoresponsive tumor-targeted drug delivery systems for the release of therapeutic payloads in response to temperature changes. Herein, a NIPAAm microgel (MP) that is responsive to temperature and pH was designed for the smart delivery of Dox. MP was made from NIPAAm, and polyethylene glycol methyl ether methacrylate (PEGMA) was copolymerized with 5%, 10%, or 15% mol of methacryloylamido hexanoic acid, (CAM5) an amphiphilic acid. We characterized the microgels using FTIR-ATR, DLS, and FESEM. The MP 10% CAM5 exhibited a particle size of 268 nm, with a transition temperature of 44 °C. MP had a drug loading capacity of 13% and entrapment efficiency of 87%. Nearly 100% of the Dox was released at pH 5 and 42 °C, compared to 30% at pH 7.4 and 37 °C. MP 10% CAM5 showed cytocompatibility in HeLa cells using the MTT assay. However, the cell viability assay showed that dox-MP was twice as effective as free Dox. Specifically, 3 μg/mL of free Dox resulted in 74% cell viability, while the same doses of Dox in NP reduced it to 35%. These results are promising for the future tumor-targeted delivery of antineoplastic-drugs, as they may reduce the side effects of Dox.

This study investigates the fabrication and characterization of electrospun poly (ε-caprolactone)/poly (vinyl pyrrolidone) (PCL/PVP) fibers integrated with a nanocomposite of chitosan, silver nanocrystals, and graphene oxide (ChAgG), aimed at developing advanced wound dressing materials. The ChAgG nanocomposite, recognized for its antimicrobial and biocompatible properties, was incorporated into PCL/PVP fibers through electrospinning techniques. We assessed the resultant fibers' morphological, physicochemical, and mechanical properties, which exhibited significant enhancements in mechanical strength and demonstrated effective antimicrobial activity against common bacterial pathogens. The findings suggest that the PCL/PVP-ChAgG fibers maintain biocompatibility and facilitate controlled therapeutic delivery, positioning them as a promising solution for managing chronic and burn-related wounds. This study underscores the potential of these advanced materials to improve healing outcomes cost-effectively, particularly in settings plagued by high incidences of burn injuries. Further clinical investigations are recommended to explore these innovative fibers' full potential and real-world applicability., (© 2024. The Author(s).)

This study evaluates the antimicrobial efficacy of chitosan nanoparticles (CNPs), varying in size, against clinical isolates of Mycobacterium tuberculosis (MTB), E. coli , S. aureus , E. faecalis , and C. albicans , as well as the antimicrobial effects of aqueous extracts and lyophilized powders of Allium (garlic) species. CNPs were synthesized through ionotropic gelation and characterized by Z potential, hydrodynamic diameter (dynamic light scattering, DLS), and SEM. Aqueous garlic extracts were prepared via decoction. We assessed antimicrobial activity using disk diffusion and broth microdilution methods; in addition, a modified agar proportion method in blood agar was used for antimicrobial activity against MTB. CNPs inhibited MTB growth at 300 μg for 116.6 nm particles and 400 μg for 364.4 nm particles. The highest antimicrobial activity was observed against E. faecalis with nanoparticles between 200 and 280 nm. Allium sativum extract produced inhibition for C. albicans at 100 μg. The results indicate that CNPs possess significant antimicrobial properties against a range of pathogens, including MTB, at high concentrations. On the other hand, aqueous Allium sativum extracts exhibited antimicrobial activity. Nonetheless, due to their instability in solution, the use of lyophilized Allium sativum powder is preferable.

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of "local" when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation., Competing Interests: Declaration of interests K.G.A. has received consulting fees on SARS-CoV-2 and the COVID-19 pandemic., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We synthesized seven ( Z )-benzylidene-2-( E )-styryloxazol-5(4 H )-ones derivatives of cinnamic acid and evaluated the ability of these compounds to inhibit human acetylcholinesterase (hAChE). The most potent compound was evaluated for cognitive improvement in short-term memory. The seven compounds reversibly inhibited the hAChE between 51 and 75% at 300 μM, showed an affinity ( K i ) from 2 to 198 μM, and an IC 50 from 9 to 246 μM. Molecular docking studies revealed that all binding moieties are involved in the non-covalent interactions with hAChE for all compounds. In addition, in silico pharmacokinetic analysis was carried out to predict the compounds' blood-brain barrier (BBB) permeability. The most potent inhibitor of hAChE significantly improved cognitive impairment in a modified Y-maze test (5 μmol/kg) and an Object Recognition Test (10 μmol/kg). Our results can help the rational design of hAChE inhibitors to work as potential candidates for treating cognitive disorders.

Nanofibers, which are formed by the electrospinning process, are used in a variety of applications. For this purpose, a specific diameter suited for each application is required, which is achieved by varying a set of parameters. This parameter adjustment process is empirical and works by trial and error, causing high input costs and wasting time and financial resources. In this work, an artificial neural network model is presented to predict the diameter of polyethylene nanofibers, based on the adjustment of 15 parameters. The model was trained from 105 records from data obtained from the literature and was then validated with nine nanofibers that were obtained and measured in the laboratory. The average error between the actual results was 2.29%. This result differs from those taken in an evaluation of the dataset. Therefore, the importance of increasing the dataset and the validation using independent data is highlighted.

Background: Persons submitted to bariatric metabolic surgery present micronutrient deficiency before and after surgery, due to the lack of proper supplementation. The aim of this study is to establish the prevalence of micronutrient deficiency in people before and after bariatric metabolic surgery in Latin America., Methods: This review was conducted in accordance with the 2020 PRISMA Guidelines., Results: Twenty-seven studies and 2135 participants were included. The highest prevalence of deficiency before surgery was reported for vitamin D (74%), zinc (71%), and hemoglobin (62%); after surgery, they were vitamin A (90.6%), vitamin D (90%), and zinc (68%)., Conclusions: There is a high prevalence of micronutrient deficiency before and after bariatric metabolic surgery from Latin American persons; the micronutrients with the highest deficiency prevalence were vitamin D before and vitamin A after bariatric metabolic surgery., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The primary mechanism for neuron death after an ischemic stroke is excitotoxic injury. Excessive depolarization leads to NMDA-mediated calcium entry to the neuron and, subsequently, cellular death. Therefore, the inhibition of the NMDA channel has been proposed as a neuroprotective measure in ischemic stroke. The high morbimortality associated with stroke warrants new therapies that can improve the functional prognosis of patients. Memantine is a non-competitive NMDA receptor antagonist which has gained attention as a potential drug for ischemic stroke. Here we analyze the available preclinical and clinical evidence concerning the use of memantine following an ischemic stroke. Preclinical evidence shows inhibition of the excitotoxic cascade, as well as improved outcomes in terms of motor and sensory function with the use of memantine. The available clinical trials of high-dose memantine in patients poststroke have found that it can improve patients' NIHSS and Barthel index and help patients with poststroke aphasia and intracranial hemorrhage. These results suggest that memantine has a clinically relevant neuroprotective effect; however, small sample sizes and other study shortcomings limit the impact of these findings. Even so, current studies show promising results that should serve as a basis to promote future research to conclusively determine if memantine does improve the outcomes of patients' post-ischemic stroke. We anticipate that future trials will fill current gaps in knowledge, and these latter results will broaden the therapeutic arsenal for clinicians looking to improve the prognosis of patients poststroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pichardo-Rojas, Pichardo-Rojas, Cornejo-Bravo and Serrano-Medina.)

Nanomedicine is a new discipline resulting from the combination of nanotechnology and biomedicine. Nanomedicine has contributed to the development of new and improved treatments, diagnoses, and therapies. In this field, nanoparticles have notable importance due to their unique properties and characteristics, which are useful in different applications, including tissue engineering, biomarkers, and drug delivery systems. Electrospinning is a versatile technique used to produce fibrous mats. The high surface area of the electrospun mats makes them suitable for applications in fields using nanoparticles. Electrospun mats are used for tissue engineering, wound dressing, water-treatment filters, biosensors, nanocomposites, medical implants, protective clothing materials, cosmetics, and drug delivery systems. The combination of nanoparticles with nanofibers creates hybrid systems that acquire properties that differ from their components' characteristics. By utilizing nanoparticles and nanofibers composed of dissimilar polymers, the two synergize to improve the overall performance of electrospinning mats and nanoparticles. This review summarizes the hybrid systems of polymeric nanoparticles and polymeric nanofibers, critically analyzing how the combination improves the properties of the materials and contributes to the reduction of some disadvantages found in nanometric devices and systems.

Objective: the aim of the present article was to test a self-care model explained by the relationship between self-efficacy, body image, obsessive-compulsive disorder, and depression in people with bariatric surgery in the city of Tijuana, Baja California, Mexico., Method: this was a correlational cross-sectional study carried out between August and December 2020. Validated instruments were administered to 102 participants to measure their self-care capacity, general self-efficacy, psychopathological symptoms, and body image perception and satisfaction. The variables of interest were analyzed using descriptive statistics and the Pearson and Spearman correlation coefficients were used to develop a model using path analysis., Result: a significant model was obtained with adequate goodness-of-fit indicators (chi-square χ2 (8) = 11.451, p = .177; root mean square error of approximation (RMSEA)= 0.000; goodness-of-fit index (GFI)= 0.965; comparative fit index (CFI)= 0.985; parsimonious normed fit index (PNFI)= 0.509, and Akaike information criterion (AIC)= 37.451). Self-efficacy (Zβ=0.294) and body image dissatisfaction (So= -0.376) were shown to influence self-care abilities while psychopathological symptoms influenced body dissatisfaction: obsessive-compulsive disorder (Zβ=0.370) and depression (Zβ=0.320)., Conclusion: adequate levels of self-efficacy and body satisfaction predict a high capacity for self-care.

The spontaneous interaction between human papillomavirus type 16 (HPV16) L1 virus-like particles (VLPs) and non-functionalized gold nanoparticles (nfGNPs) interferes with the nfGNPs' salt-induced aggregation, inhibiting the red-blue color shift in the presence of NaCl. Electron microscopy and competition studies showed that color-shift inhibition is a consequence of direct nfGNP-VLP interaction and, thus, may produce a negative impact on the virus entry cell process. Here, an in vitro infection system based on the HPV16 pseudovirus (PsV) was used to stimulate the natural infection process in vitro. PsVs carry a pseudogenome with a reporter gene, resulting in a fluorescent signal when PsVs infect a cell, allowing quantification of the viral infection process. Aggregation assays showed that nfGNP-treated PsVs also inhibit color shift in the presence of NaCl. High-resolution microscopy confirmed nfGNP-PsV complex formation. In addition, PsVs can interact with silver nanoparticles, suggesting a generalized interaction of metallic nanoparticles with HPV16 capsids. The treatment of PsVs with nfGNPs produced viral infection inhibition at a higher level than heparin, the canonical inhibitor of HPV infection. Thus, nfGNPs can efficiently interfere with the HPV16 cell entry process and may represent a potential active component in prophylactic formulations to reduce the risk of HPV infection.

Augmenting bacterial growth is of great interest to the biotechnological industry. Hence, the effect of poly (caprolactone) fibrous scaffolds to promote the growth of different bacterial strains of biological and industrial interest was evaluated. Furthermore, different types of carbon (glucose, fructose, lactose and galactose) and nitrogen sources (yeast extract, glycine, peptone and urea) were added to the scaffold to determinate their influence in bacterial growth. Bacterial growth was observed by scanning electron microscopy; thermal characteristics were also evaluated; bacterial cell growth was measured by ultraviolet-visible spectrophotometry at 600-nm. Fibers produced have an average diameter between 313 to 766 nm, with 44% superficial porosity of the scaffolds, a glass transition around ~64 °C and a critical temperature of ~338 °C. The fibrous scaffold increased the cell growth of Escherichia coli by 23% at 72 h, while Pseudomonas aeruginosa and Staphylococcus aureus increased by 36% and 95% respectively at 48 h, when compared to the normal growth of their respective bacterial cultures. However, no significant difference in bacterial growth between the scaffolds and the casted films could be observed. Cell growth depended on a combination of several factors: type of bacteria, carbon or nitrogen sources, casted films or 3D scaffolds. Microscopy showed traces of a biofilm formation around 3 h in culture of P. aeruginosa . Water bioremediation studies showed that P. aeruginosa on poly (caprolactone)/Glucose fibers was effective in removing 87% of chromium in 8 h.

Background and Objectives: Micronutrient deficiencies are common among bariatric patients; this study aimed to determine whether a cognitive dissonance-based virtual program improved adherence to multivitamin use in bariatric patients from northern Mexico., Methods and Study Design: A randomized controlled trial of the supplementation strategy was conducted over three months. The participants were randomized to an intervention or waitlisted control group and received two psycho-educative and four cognitive dissonance virtual sessions. Multiple linear regression was used to determine standardized estimates of associations between the intervention and dependent variables. Two path analyses were evaluated considering baseline and post-test measurements., Results: Intervention was associated with higher concentrations of Hb (β=0.758, p<0.001), vitamin D (β=0.577, p<0.001), iron (β=0.523, p<0.001), folate (β=0.494, p<0.01), calcium (β=0.452, p<0.01), higher adherence (β=0.467, p<0.001), and level of knowledge (β=0.298, p<0.05., Conclusions: The dissonance-based intervention potentiated the level of supplementation adherence. A higher level of adherence was reflected in micronutrient concentrations, thus providing confirmation of intervention. Thus, support is found for a multidisciplinary clinical practice that enhances nutrition status after bariatric surgery for obesity.

New medical devices with anti-inflammatory properties are critical to prevent inflammatory processes and infections in medical/surgical procedures. In this work, we present a novel functionalization of silicone for medical use with a polymeric prodrug and a thermosensitive polymer, by graft polymerization (gamma rays), for the localized release of salicylic acid, an analgesic, and anti-inflammatory drug. Silicone rubber (SR) films were functionalized in two stages using graft polymerization from ionizing radiation ( 60 Co). The first stage was grafting poly( N -vinylcaprolactam) (PNVCL), a thermo-sensitive polymer, onto SR to obtain SR- g -PNVCL. In the second stage, poly(2-methacryloyloxy-benzoic acid) (P2MBA), a polymeric prodrug, was grafted to obtain (SR- g -PNVCL)- g -P2MBA. The degree of functionalization depended on the concentrations of monomers and the irradiation dose. The films were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy/energy-dispersive X-ray spectrometry (SEM-EDX), thermogravimetric analysis (TGA), and contact angle. An upper critical solution temperature (UCST) of the films was demonstrated by the swelling degree as a temperature function. (SR- g -PNVCL)- g -P2MBA films demonstrated hydrolysis-mediated drug release from the polymeric prodrug, pH, and temperature sensitivity. GC-MS confirmed the presence of the drug (salicylic acid), after polymer hydrolysis. The concentration of the drug in the release media was quantified by HPLC. Cytocompatibility and thermo-/pH sensitivity of functionalized medical silicone were demonstrated in cancer and non-cancer cells.

Objectives: To summarize the procedure for reporting adverse drug reactions (ADRs) in a Mexican hospital, with the purpose of promoting and facilitating the report of ADRs by the heath team. We outline the relevance of pharmacists in performing these activities in Mexican hospitals., Methods: A pharmacovigilance study was carried out following the establishment of the Pharmacovigilance Unit of a Mexican hospital on January 2014 through March 2019., Key Findings: There is an undernotification rate of ADRs, since only 137 ADRs were notified in a five-year period, mostly by biopharmaceutical chemists holding bachelor's degrees that were acting as pharmacists., Conclusions: To improve the safety of medications, it is necessary to improve ADR notifications in Mexico's health system. One important step in this direction is to establish a Pharmacy degree with training for promoting and performing ADR notifications., (© 2020 Royal Pharmaceutical Society.)

Silicone rubber (SR) is a material used for medical procedures, with a common example of its application being in implants for cosmetic or plastic surgeries. It is also an essential component for the development of medical devices. SR was functionalized with the polymeric prodrug of poly(2-methacryloyloxy-benzoic acid) (poly(2MBA)) to render the analgesic anti-inflammatory drug salicylic acid by hydrolysis. The system was designed by functionalizing SR films (0.5 cm × 1 cm) with a direct grafting method, using gamma irradiation ( 60 Co source) to induce the polymerization process. The absorbed dose (from 20 to 100 kGy) and the monomer concentration (between 0.4 and 1.5 M) were critical in controlling the surface and the bulk modifications of SR. Grafting poly(2MBA) onto SR (SR- g -2MBA) were characterized by attenuated total reflectance Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy/energy-dispersive X-ray spectrometry, fluorescence microscopy, the contact angle, and the swelling. SR-g-2MBA demonstrated the drug's sustained and pH-dependent release in simulated physiological mediums (pH = 5.5 and 7.4). The drug's release was quantified by high-performance liquid chromatography and confirmed by gas chromatography-mass spectrometry. Finally, cytocompatibility was demonstrated in murine fibroblast and human cervical cancer cell lines. The developed systems provide new polymeric drug release systems for medical silicone applications.

This study aims to determine the degree of acetylcholinesterase inhibition and neurological symptoms for each of the psychiatric disorders diagnosed in the farm workers of a rural population in the state of Baja California, Mexico. We conducted a cross-sectional study on 140 agricultural workers (exposed participants). The study was run using the Mini International Neuropsychiatric Interview Diagnostic Test (MINI), a pre-established questionnaire to diagnose the mental state of each agricultural worker. Analysis of enzymatic activity was carried out using the modified Ellman method. The results showed that, among agricultural workers with slightly inhibited enzymatic activity, 25% met the criteria for the diagnosis of major depression with suicidal attitudes, 23.9% with inhibited enzymatic activity showed generalized anxiety, 23.5% showed combined depression⁻anxiety, and 22% met the criteria for major depression and no psychiatric diagnosis disorder. These results suggest the need for the development of effective public-health strategies to inform farm workers about integrated pesticide management in order to prevent serious health complications.

The electrospinning technique is a useful and versatile approach for conversion of polymeric solutions into continuous fibers, ranging from a few micrometers (10-100 μm) to the scale of nanometers (10- 100 nm) in diameters. This technique can be used in a vast number of polymers, in some cases after modifying them to the required properties. The high surface-to-volume ratio of the fibers can improve some processes like cell binding and proliferation, drug loading, and mass transfer processes. One of the most important and studied areas of electrospinning is in the drug delivery field, for the controlled release of active substances ranging from antibiotics and anticancer agents, to macromolecules such as proteins and DNA. The advantage of this method is that a wide variety of low solubility drugs can be loaded into the fibers to improve their bioavailability or to attain controlled release. This review presents an overview of the reported drugs loaded into electrospun polymeric nanofibers to be used as drug delivery systems. These drugs are classified by their applications in pharmacy.

Population pharmacokinetic (PopPK) models allow researchers to predict and analyze drug behavior in a population of individuals and to quantify the different sources of variability among these individuals. In the development of PopPK models, the most frequently used method is the nonlinear mixed effect model (NLME). However, once the PopPK model has been developed, it is necessary to determine if the selected model is the best one of the developed models during the population pharmacokinetic study, and this sometimes becomes a multiple criteria decision making (MCDM) problem, and frequently, researchers use statistical evaluation criteria to choose the final PopPK model. The used evaluation criteria mentioned above entail big problems since the selection of the best model becomes susceptible to the human error mainly by misinterpretation of the results. To solve the previous problems, we introduce the development of a software robot that can automate the task of selecting the best PopPK model considering the knowledge of human expertise. The software robot is a fuzzy expert system that provides a method to systematically perform evaluations on a set of candidate PopPK models of commonly used statistical criteria. The presented results strengthen our hypothesis that the software robot can be successfully used to evaluate PopPK models ensuring the selection of the best PopPK model.

Background: Factors associated with candidiasis and colonization in HIV-positive children and adolescents in developing countries are not well understood., Aim: To identify the factors associated with oral Candida colonization and candidiasis in institutionalized HIV-positive children and adolescents in Tijuana, México, as well as the response of the isolates to antifungals., Materials and Methods: Sample of the oral mucosa of 30 HIV positive children and adolescents were obtained to isolate and identify Candida species by culture and metabolic profile. Antifungal drugs susceptibility was determined according to CLSI. Indicators of immunological and virologic failure were classified in accordance to WHO criteria., Results: Six Candida species were identified from oral mucosa, 53% colonizers and 47% in candidiasis. Factors associated with candidiasis and oral colonization were viral load (p = 0,001), CD4+ counts (p = 0,002) and HAART regimen (p ≤ 0,014). The most prevalent species was C. glabrata (33%), but C. albicans (27%) was more resistant to fluconazole (p = 0,001). Itraconazol resistant species were identified in regimens that include an NNRTI (p = 0,041)., Conclusion: HIV-positive children and adolescents living in an orphanage showed high prevalence of colonizing Candida spp. and resistance to antifungals, related to NNRTI.

Recently, electrospun polymeric nanofibers have proven to be an interesting strategy for drug delivery systems application. The high surface-to-volume ratio of the fibers can improve some processes, such as cell binding and proliferation, drug loading, and mass transfer processes. One of the most important and studied areas of electrospinning is in the drug delivery field, for the controlled release of active substances ranging from antibiotics and anticancer agents to macromolecules such as proteins and DNA. The advantage of this method is that a wide variety of low solubility drugs can be loaded into the fibers to improve their bioavailability or to attain controlled release. This review presents an overview of the reported drugs loaded into polymeric nanofibers, to be used as drug delivery systems. For instance, it presents the reports on drugs with different bioactivities such as antiinflammatory, anti-microbial, anticancer, cardiovascular, anti-histamine, gastrointestinal, palliative and contraceptive drugs, etc. It also analyzes the electrospinning techniques used in each system, as well as the polymers used as matrices for the preparation of the nanofibers; unfolding the advantages of electrospun polymeric nanofibers over other drug delivery systems. This review intends to enlist and summarize the reported literature concerning this topic. In addition, it proposes future research in the field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Through studies with ligand binding to the acetylcholine binding protein (AChBP), we previously identified a series of 4,6-substituted 2-aminopyrimidines that associate with this soluble surrogate of the nicotinic acetylcholine receptor (nAChR) in a cooperative fashion, not seen for classical nicotinic agonists and antagonists. To examine receptor interactions of this structural family on ligand-gated ion channels, we employed HEK cells transfected with cDNAs encoding three requisite receptor subtypes: α7-nAChR, α4β2-nAChR, and a serotonin receptor (5-HT 3A R), along with a fluorescent reporter. Initial screening of a series of over 50 newly characterized 2-aminopyrimidines with affinity for AChBP showed only two to be agonists on the α7-nAChR below 10 μM concentration. Their unique structural features were incorporated into design of a second subset of 2-aminopyrimidines yielding several congeners that elicited α7 activation with EC 50 values of 70 nM and K d values for AChBP in a similar range. Several compounds within this series exhibit specificity for the α7-nAChR, showing no activation or antagonism of α4β2-nAChR or 5-HT3AR at concentrations up to 10 μM, while others were weaker antagonists (or partial agonists) on these receptors. Analysis following cocrystallization of four ligand complexes with AChBP show binding at the subunit interface, but with an orientation or binding pose that differs from classical nicotinic agonists and antagonists and from the previously analyzed set of 2-aminopyrimidines that displayed distinct cooperative interactions with AChBP. Orientations of aromatic side chains of these complexes are distinctive, suggesting new modes of binding at the agonist-antagonist site and perhaps an allosteric action for heteromeric nAChRs.

Medical devices decorated with salicylic acid-based polymer chains (polymeric prodrug) that slowly release this anti-inflammatory and anti-biofilm drug at the implantation site were designed. A "grafting from" method was implemented to directly grow chains of a polymerizable derivative of salicylic acid (2-methacryloyloxy-benzoic acid, 2MBA) onto polypropylene (PP). PP was modified both at bulk and on the surface with poly(2MBA) by means of an oxidative pre-irradiation method ((60)Co source), in order to obtain a grafted polymer in which salicylic acid units were linked by means of labile ester bonds. The grafting percent depended on absorbed dose, reaction time, temperature and monomer concentration. The functionalized films were analyzed regarding structure (FTIR-ATR, SEM-EDX, fluorescence microscopy), temperature stability (TGA), interaction with aqueous medium (water contact angle and swelling), pH-responsive release and cytocompatibility (fibroblasts). In the obtained poly(2MBA)-grafted biomaterial, poly(2MBA) behaved as a polymeric prodrug that regulates salicylic acid release once in contact with aqueous medium, showing pH-dependent release rate., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Nowadays, electrospinning has become one of the most versatile, easy, and cost-effective techniques to engineer advanced materials used for many applications, especially in the biomedical and environmental areas. Like the numerous patents around the world, the increasing number of papers witnesses the huge potential of this simple process, and many companies have been emerged during the last years to exploit its innumerable applications. This article presents a critically selected overview of polymers that can be used to produce nanofibers, along with the biomedical applications of the resulting electrospun scaffolds. We have focused on about seven natural and synthetic polymers, but many more can be found in the literature, either as their pristine state or as composites with ceramics, metals, and other polymers. The description of some strategies for nanofiber production, and the characterization used to evaluate their optimization, has been discussed. Finally, several polymers have been recognized as highlights for future work.

Poly(carboxyalkyl methacrylates) were studied as a cationic-drug delivery system, at pH 6.8 and 8.0. Different polymer/drug complexes were used to prepare compressed tablets. By kinetics experiments, we have found that drug release is dependent on both the hydrophobicity of the whole complex and the pH of the environment. Furthermore, a mechanism of dissociation/erosion clearly describes the drug release from a complex formed by a polymer soluble at target pH; otherwise, a mechanism of dissolution/diffusion is depicted. Additionally, we have observed that hydrophilic fillers increase the drug release rate. Since our results using different polymer/drug complexes exhibit pH-sensitive drug release, we propose that the poly(carboxyalkyl methacrylates) have potential as a colon-specific drug-delivery system., (© 2012 Informa Healthcare USA, Inc.)

The synthesis and properties of thermal/pH-sensitive core-shell copolymer nano/microgels were investigated. The crosslinked core consisted of N-isopropylacrylamide (NIPAAm) while the shell was stabilized by poly(ethylene glycol) methyl ether methacrylate (PEGMA) and 2-methacryloyloxybenzoic acid (2MBA) using a "one pot" soapless emulsion polymerization method. Monodisperse particles were produced with average hydrodynamic diameters ranging from 40 to 880 nm, as determined by dynamic light scattering (DLS) in water at 25°C, depending on the synthetic recipe used. The influence of PEGMA and 2MBA content on size and temperature transition at different pH values was studied. Zeta potential measurements and acid-base titration studies demonstrated almost complete incorporation of acid comonomer (2MBA) into the nano/microgels. Two different crosslinkers, a stable and an acid labile, were compared. The crosslinker used has a major influence on the size and charge density of the nano/microgels produced. Microscopic studies confirmed the core-shell morphology of the nano/microgels., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: A vancomycin population pharmacokinetic prediction model for adult and elderly patients was developed using NONMEM. The predictability of the model was studied and compared with ten other models., Methods: Data were collected from routine care of 141 subjects. NONMEM was used to derive a population model. After internal evaluation using the bootstrap technique, external validation was studied using an independent dataset that consisted of 95 subjects; a statistical comparison of precision and bias was conducted., Results: A two-compartment open model was derived with body weight, age, and CLcr as covariates. The bootstrap process showed stability of the model. A comparison of subjects older and younger than 65 years found that the older group had a mean clearance of 2.24 (+/- 1.2) l/h compared to 4.03 (+/- 1.7) l/h, and a peripheral volume of 43.7 (+/- 5.1) l compared to 28.4 (+/- 5.3) l compared to younger patients. These values were modeled using CLcr in the clearance equation and Vd as a function of age. The eleven models studied showed a bias in predicting serum concentrations from the test database that ranged from 0.35 mg/l to -5.93 mg/l. Precision ranged from 4.53 mg/l to 8.05 mg/l. Our method ranked in fourth place overall and when compared statistically its bias was different from the method that ranked in second place by -1.45 (95% CI -2.46, -0.42; p = 0.005), and different from all the methods that ranked worse. The only difference in precision was with the method that ranked in eleventh place with a relative precision of 0.49 (95% CI 0.27, 0.70; p < 0.001)., Conclusions: A two-compartment open model fitted the data with weight, age, and CLcr as covariates. The derived method ranked in fourth place overall. The two-compartment nature of two of the equations studied did not provide an advantage. A future study with more data in the distribution phase could provide a model with better predictability.

PDI enzymes are oxidoreductases that catalyze oxidation, reduction and isomerization of disulfide bonds in polypeptide substrates. We have previously identified an E. histolytica PDI enzyme (EhPDI) that exhibits oxidase activity in vivo. However, little is known about the specific role of its redox-related structural features on the enzymatic activity. Here, we have studied the in vivo oxidative folding of EhPDI by mutagenic analysis and functional complementation assays as well as the in vitro oxidative folding and reductive activities by comparative kinetics using functional homologues in standard assays. We have found that the active-site cysteine residues of the functional domains (Trx-domains) are essential for catalysis of disulfide bond formation in polypeptides and proteins, such as the bacterial alkaline phosphatase. Furthermore, we have shown that the recombinant EhPDI enzyme has some typical properties of PDI enzymes: oxidase and reductase activities. These activities were comparable to those observed for other functional equivalents, such as bovine PDI or bacterial thioredoxin, under the same experimental conditions. These findings will be helpful for further studies intended to understand the physiological role of EhPDI.

Agonists activating nicotinic acetylcholine receptors (nAChR) include potential therapeutic agents and also toxicants such as epibatidine and neonicotinoid insecticides with a chloropyridinyl substituent. Nicotinic agonist interactions with mollusk (Aplysia californica) acetylcholine binding protein, a soluble surrogate of the nAChR extracellular domain, are precisely defined by scanning with 17 methionine and tyrosine mutants within the binding site by photoaffinity labeling with 5-azido-6-chloropyridin-3-yl probes that have similar affinities to their nonazido counterparts. Methionine and tyrosine are the only residues found derivatized, and their reactivity exquisitely depends on the direction of the azido moiety and its apposition to the reactive amino acid side chains.

Isoniazid (INH) is a drug extensively used as a prophylactic and therapeutic agent for human tuberculosis (TB). INH is metabolized by the enzymatic activity of N-acetyltransferase 2 (NAT2). Human NAT2, encoded by a highly polymorphic gene, is involved in the biotransformation of xenobiotics, including drugs and certain chemical carcinogens. Numerous studies have established the correlation between the acetylator phenotype and the NAT2 genotype in several populations; however, little is known regarding Latin-American populations and the pharmacogenetics of NAT2. Here, we report the molecular genotyping of the NAT2 gene, the acetylator phenotype, and the incidence of INH-related adverse reactions in a group of 25 Mexican individuals enrolled in a prophylactic protocol for TB. Using both the NAT2 genotyping and acetylation phenotyping approach, we found a ratio of 69.2 and 30.8% of slow and fast acetylators, respectively. Concordance of the NAT2 genotype and phenotype classification was 88% in the bimodal model. Regarding INH-related adverse reactions, only 2 individuals (8%) exhibited declared gastric intolerance. In our study group, we found an association between the NAT2 genotype and acetylator phenotype (OR=7.78, 95% CI, 0.87-87.98, Fisher's exact test, p<0.05), but did not find any genotype or phenotype association with the incidence of INH-related adverse reactions (Fisher's exact test, p>0.05).

Protein disulfide isomerase (PDI) enzymes are eukaryotic oxidoreductases that catalyze the correct formation of disulfide bonds during protein folding. Structurally they are characterized by the presence of functional thioredoxin-like (Trx) domains. For the protozoan parasite causative of the human amebiasis (Entamoeba histolytica), the correct formation of disulfide bonds is important for an accurate folding of its proteins, including some virulence factors. However, little is known about the enzymes involved in this mechanism. We undertook a post-genomic approach to identify the PDI family of this parasite. The genome database survey revealed a set of 11 PDI-encoding sequences with predictable protein thiol/disulfide oxidoreductase activities.

Carboxyalkyl methacrylates, a new class of non-cross-linked, hydrophobic weak polyelectrolytes, were synthesized, and then bound to cationic drugs (propranolol.HCl, diltiazem.HCl and verapamil.HCl) to form water-insoluble complexes that release the bound drug only in ionic media (pH 7.4). Compressed tablets were prepared from these cation exchange polyelectrolytes. Release profiles followed zero order kinetics (n>0.90; n is the release exponent). As the hydrophobicity of the polyelectrolytes increased, the rate of release decreased and deviated from linearity (n=0.7). Both the ionic strength of the medium as well as the solubility of the drug affected the rate of release. In acidic media (pH 1.2) a burst of drug was released but the release was halted by a layer of non-ionized polymer precipitated on the surface of the tablets. The results indicate that it is possible to "tailor-make" the release kinetics by using a polyelectrolyte from the series with the suitable hydrophobicity.

Purpose: The purpose of this work was to 1) investigate the effect of sucrose esters (sucrose oleate and sucrose laureate in water or in Transcutol, TC) on the stratum corneum (SC) barrier properties in vivo and 2) examine the impact of these surfactant-like molecules on the in vivo percutaneous penetration of a model penetrant 4-hydroxybenzonitrile (4-HB)., Methods: Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and transepidermal water loss measurements were used to evaluate the sucrose oleate- and sucrose laureate-induced biophysical changes in SC barrier function in vivo. In addition. the effect of the enhancers on 4-HB penetration was monitored in vivo using ATR-FTIR spectroscopy in conjunction with tape-stripping of the treated site., Results: Treatment of the skin with 2% sucrose laureate or sucrose oleate in TC significantly increased the extent of 4-HB penetration relative to the control. Furthermore, when skin treated with these formulations was examined spectroscopically, the C-H asymmetric and symmetric stretching bands of the lipid methylene groups were characterized by 1) decreased absorbances and 2) frequency shifts to higher wavenumbers. These effects on the SC lipids and 4-HB penetration were more pronounced for sucrose laureate when combined with TC., Conclusions: A combination of sucrose esters (oleate or laureate) and TC is able to temporally alter the stratum corneum barrier properties, thereby promoting 4-HB penetration. These molecules are worthy of further investigation as potential candidates for inclusion in transdermal formulations as penetration enhancers.

The bioadhesive properties of the hydrophobic, basic polyelectrolyte hydrogel disks containing crosslinked N,N-dimethylaminoethyl methacrylate-co-methyl methacrylate 30/70mol% were evaluated in vitro using gastric (pH 1.2), sublingual (pH 6.5), vaginal (pH 4.0) and intestinal (pH 7.5) pig's mucosas. Adhesive strength was measured using a modified Du Noüy tensiometer by measuring the force of detachment between a gel disk and the respective mucosa. The effect of crosslinker content in the gel was evaluated. It was found an increase in the adhesive strength with the increase of crosslinker content in the pH range of 4.0-7.5. For the evaluation at pH 1.2 (gastric mucosa) the opposite behavior was observed. The results indicate that initial bioadhesive contact may be the result of surface energy effects and/or electrostatic interactions of oppositely charged groups between mucin and the gel. In some cases, mucus dehydration may also be involved. When the gel is swollen, chain interpenetration also plays a roll in the bioadhesive interaction. The gels presented bioadhesive forces in gastric and vaginal mucosas (acidic medium), similar to the adhesive forces of well-known bioadhesives such as hydroxymethylcellulose and sodium alginate to the intestinal mucosa. The results indicate that hydrophobic polybasic gels present bioadhesive properties that make them suitable for site specific, pH controlled drug delivery.

Copolymers of N, N-diethylaminoethyl methacrylate (DEA) and methyl methacrylate (MMA) were synthesized in ethanolic solution and characterized in terms of reactivity ratios, densities and water vapour sorption. For the reaction conditions studied the copolymerization is essentially random. Polymer densities, determined by centrifugation in a density gradient, range from 1.10 for pDEA to 1.13 for p(DEA/MMA) 52/48 mol%. Flory-Huggins chi parameters were determined by isopiestic water vapour sorption, and were found to depend on both the comonomer ratio and the water content. An exceptionally strong dependence of chi on water content (or equivalently, polymer volume fraction) suggests that Flory-Huggins theory is not the proper theory to apply, especially for the polymers with the highest MMA content. Analysis of the data in terms of the Zimm-Lundberg cluster theory reveals that as the polymer becomes more hydrophobic and glassy with increased MMA, the sorption becomes more nonuniform in the polymer.