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The intranasal administration of drugs using environmentally responsive formulations, employing a combination of hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (P407), can result in release systems that may assist in the treatment of neurological diseases. Meloxicam, considered a potential adjuvant in the treatment of Alzheimer's disease, could be used in these platforms. The aim of this work was to develop a mucoadhesive, thermoresponsive, and nanostructured system containing HPMC for nose-to-brain administration of meloxicam. The initially selected systems were investigated for their rheological, mechanical, and micellar size characteristics. The systems were dilatant at 25 °C and pseudoplastic with a yield value at 37 °C, showing viscoelastic properties at both temperatures. The platform containing HPMC (0.1%, w/w) and P407 (17.5%, w/w) was selected and demonstrated good mucoadhesive properties, along with an appropriate in vitro release profile. HPMC could form a binary system with P407, displaying superior mucoadhesive and thermoresponsive properties for nose-to-brain meloxicam administration, indicating that the selected formulation is worthy of clinical studies.
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Encéfalo , Poloxâmero , Administração Intranasal , Derivados da Hipromelose , Meloxicam , Encéfalo/metabolismo , MetilceluloseRESUMO
Erythrosine displays potential photodynamic activity against microorganisms and unhealthy cells. However, erythrosine has high hydrophilicity, negatively impacting on permeation through biological membranes. Combining biological macromolecules and thermoresponsive polymers may overcome these erythrosine-related issues, enhancing retention of topically applied drugs. The aim of this work was to investigate the performance of adhesive and thermoresponsive micellar polymeric systems, containing erythrosine in neutral (ERI) or disodium salt (ERIs) states. Optimized combinations of poloxamer 407 (polox407) and sodium carboxymethylcellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) were used as platforms for ERI/ERIs delivery. The rheological and mechanical properties of the systems was explored. Most of the formulations were plastic, thixotropic and viscoelastic at 37 °C, with suitable gelation temperature for in situ gelation. Mechanical parameters were reduced in the presence of the photosensitizer, improving the softness index. Bioadhesion was efficient for all hydrogels, with improved parameters for mucosa in contrast to skin. Formulations composed of 17.5 % polox407 and 3 % HPMC or 1 % NaCMC with 1 % (w/w) ERI/ERIs could release the photosensitizer, reaching different layers of the skin/mucosa, ensuring enough production of cytotoxic species for photodynamic therapy. Functional micelles could boost the photodynamic activity of ERI and ERIs, improving their delivery and contact time with the cells.
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Adesivos , Celulose , Eritrosina/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Poloxâmero , Polímeros , Derivados da HipromeloseRESUMO
Recently, the number of new cases of cutaneous leishmaniasis has been of concern among health agencies. Research that offers new therapeutic alternatives is advantageous, especially those that develop innovative drugs. Therefore, this paper presents the incorporation of Copaifera reticulata Ducke and chlorophyll extract into Pluronic®® F127 and Carbopol gels, under optimized polymer quantities. The chlorophyll extract (rich in photosensitizing compounds) was obtained by continuous-flow pressurized liquid extraction (PLE), a clean, environmentally friendly method. The system aims to act as as a leishmanicidal, cicatrizant, and antibiotic agent, with reinforcement of the photodynamic therapy (PDT) action. Rheological and mechanical analyses, permeation studies and bioadhesiveness analyses on human skin, and PDT-mediated activation of Staphylococcus aureus were performed. The emulgels showed gelation between 13° and 15 °C, besides pseudoplastic and viscoelastic properties. Furthermore, the systems showed transdermal potential, by releasing chlorophylls and C. reticulata Ducke into the deep layers of human skin, with good bioadhesive performance. The application of PDT reduced three logarithmic colony-forming units of S. aureus bacteria. The results support the potential of the natural drug for future clinical trials in treating wounds and cutaneous leishmania.
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Memory B cells (MBCs) generate rapid antibody responses upon secondary encounter with a pathogen. Here, we investigated the kinetics, avidity and cross-reactivity of serum antibodies and MBCs in 155 SARS-CoV-2 infected and vaccinated individuals over a 16-month timeframe. SARS-CoV-2-specific MBCs and serum antibodies reached steady-state titers with comparable kinetics in infected and vaccinated individuals. Whereas MBCs of infected individuals targeted both pre- and postfusion Spike (S), most vaccine-elicited MBCs were specific for prefusion S, consistent with the use of prefusion-stabilized S in mRNA vaccines. Furthermore, a large fraction of MBCs recognizing postfusion S cross-reacted with human betacoronaviruses. The avidity of MBC-derived and serum antibodies increased over time resulting in enhanced resilience to viral escape by SARS-CoV-2 variants, including Omicron BA.1 and BA.2 sub-lineages, albeit only partially for BA.4 and BA.5 sublineages. Overall, the maturation of high-affinity and broadly-reactive MBCs provides the basis for effective recall responses to future SARS-CoV-2 variants.
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SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.
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Nowadays, the development of mucoadhesive systems for drug delivery has gained keen interest, with enormous potential in applications through different routes. Mucoadhesion characterizes an attractive interaction between the pharmaceutical dosage form and the mucosal surface. Many polymers have shown the ability to interact with mucus, increasing the residence time of local and/or systemic administered preparations, such as tablets, patches, semi-solids, and micro and nanoparticles. Cellulose is the most abundant polymer on the earth. It is widely used in the pharmaceutical industry as an inert pharmaceutical ingredient, mainly in its covalently modified forms: methylcellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and carboxymethylcellulose salts. Aiming to overcome the drawbacks of oral, ocular, nasal, vaginal, and rectal routes and thereby maintaining patient compliance, innovative polymer blends have gained the interest of the pharmaceutical industry. Combining mucoadhesive and thermoresponsive polymers allows for simultaneous in situ gelation and mucoadhesion, thus enhancing the retention of the system at the site of administration and drug availability. Thermoresponsive polymers have the ability to change physicochemical properties triggered by temperature, which is particularly interesting considering the physiological temperature. The present review provides an analysis of the main characteristics and applications of cellulose derivatives as mucoadhesive polymers and their use in blends together with thermoresponsive polymers, aiming at platforms for drug delivery. Patents were reviewed, categorized, and discussed, focusing on the applications and pharmaceutical dosage forms using this innovative strategy. This review manuscript also provides a detailed introduction to the topic and a perspective on further developments.
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Sistemas de Liberação de Medicamentos , Polímeros , Humanos , Feminino , Polímeros/química , Adesividade , Derivados da Hipromelose , Carboximetilcelulose Sódica , Sais , Celulose , Preparações FarmacêuticasRESUMO
This study presents a phytotherapeutic emulsion-filled gel design composed of Pluronic® F127, Carbopol® C934P, and high level of copaiba oil-resin (PHY-ECO). Mathematical modeling and response surface methodology (RSM) were employed to access the optimal ratio between the oil and the polymer gel-matrix constituents. The chemometric approach showed robust mechanical and thermoresponsive properties for emulsion gel. The model predicts viscosity parameters at 35.0°C (skin temperature) from PHY-ECOs. Optimized PHY-ECOs were described by 18-20% (w/w) F127, 0.25% (w/w) C934P, and 15% (w/w) copaiba oil-resin, and showed interfacial layers properties that led to high physicochemical stability. Besides, it had thermal stimuli-responsive that led large viscosity range before and after skin administration, observed by oscillatory rheology. These behaviors give the optimized smart PHY-ECO high design potential to be used as a pharmaceutical platform for CO delivery, focusing on the anti-inflammatory therapy and skin wound care.
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Poloxâmero , Administração Cutânea , Emulsões/química , Poloxâmero/química , Reologia , ViscosidadeRESUMO
The recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity relative to the Wuhan-Hu-1 RBD and acquires binding to mouse ACE2. Severe reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for vaccinated and convalescent individuals. Most (26 out of 29) receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only three mAbs, including the ACE2-mimicking S2K146 mAb1, retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs recognizing antigenic sites outside the RBM, including sotrovimab2, S2X2593 and S2H974, neutralized Omicron. The magnitude of Omicron-mediated immune evasion and the acquisition of binding to mouse ACE2 mark a major SARS-CoV-2 mutational shift. Broadly neutralizing sarbecovirus mAbs recognizing epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.
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When developing buccal films for oromucosal drug administration, adhesion is essential to ensure sufficient time for permeation of the active ingredient(s) through the oral mucosa and avoid the detachment and subsequent swallowing of the film. In this study, biomimetic materials were evaluated as a replacement for buccal mucosa in mucoadhesion testing and potential adhesives were compared regarding their suitability to increase the adhesion of hypromellose-based oromucosal films. Gelatin gels, as possible biomimetics, failed to mimic the buccal mucosa. Furthermore, esophageal tissue lead to a wider variance of adhesion data despite showing a good correlation with buccal tissue. A synthetic copolymer hydrogel based on hydroxyethylmethacrylate (HEMA) and N-acryloyl glucosamine (AGA) was able to mimic the buccal mucosa in these tests and reduced the variation in the data compared to animal tissue. Adding polyacrylic acid and polyvinylpyrrolidone to the film formulations at a concentration of 5% w/w approximately doubled the maximum detachment force and work of adhesion. Sodium alginate enhanced the adhesive properties moderately but adding chitosan did not significantly increase mucoadhesion. Polyvinylpyrrolidone and polyacrylic acid are rated as strong adhesion enhancers for buccal films and the HEMA/AGA hydrogel is considered as a suitable alternative for animal mucosa in mucoadhesion testing.
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Biomimética , Sistemas de Liberação de Medicamentos , Adesividade , Administração Bucal , Animais , Composição de Medicamentos , Mucosa BucalRESUMO
Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naive hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.
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Psoriasis is an autoimmune, inflammatory and chronic skin disease in which cell growth and proliferation are increased, causing erythema, lesions and skin's peeling. Oral methotrexate (MTX) is the first-choice drug when phototherapy or retinoid treatment are not effective. Topical administration can be advantageous to better orientate the drug's delivery; however, the stratum corneum performs as a barrier for hydrofilic drugs penetration. This study sought to evaluate two different types of vehicles for MTX on the psoriasis treatment - hydrogel and liquid crystal systems (LCs). Lamellar and hexagonal liquid crystalline phases were selected from a ternary phase diagram based on polysorbate 80, isopropyl miristate and water. The hydrogel was based on alkylated carbomer (ACH). Rheological analysis showed ACH was more elastic than lamellar and hexagonal phases. ACH interacted better with pig skin than LCs in bioadhesion assay. Preclinical study revealed the ACH decreased inflammation in mice with induced psoriasis, being as effective as dexamethasone to regulate epidermis thickness, COX-2 and myeloperoxidase activity and TNF-α level, while LCs demonstrated inflammatory effect. Therefore, MTX-loaded hydrogel based platforms are indicated for local treatment of psoriasis and present great potential for further studies.
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Cristais Líquidos , Psoríase , Animais , Hidrogéis , Metotrexato , Camundongos , Psoríase/tratamento farmacológico , Tensoativos , SuínosRESUMO
The repeated spillovers of {beta}-coronaviruses in humans along with the rapid emergence of SARS-CoV-2 escape variants highlight the need to develop broad coronavirus therapeutics and vaccines. Five monoclonal antibodies (mAbs) were isolated from COVID-19 convalescent individuals and found to cross-react with multiple {beta}-coronavirus spike (S) glycoproteins by targeting the stem helix. One of these mAbs, S2P6, cross-reacts with more than twenty human and animal {beta}-coronavirus S glycoproteins and broadly neutralizes SARS-CoV-2 and pseudotyped viruses from the sarbecovirus, merbecovirus and embecovirus subgenera. Structural and functional studies delineate the molecular basis of S2P6 cross-reactivity and broad neutralization and indicate that this mAb blocks viral entry by inhibiting membrane fusion. S2P6 protects hamsters challenged with SARS-CoV-2 (including the B.1.351 variant of concern) through direct viral neutralization and Fc-mediated effector functions. Serological and B cell repertoire analyses indicate that antibodies targeting the stem helix are found in some convalescent donors and vaccinees but are predominantly of narrow specificity. Germline reversion of the identified cross-reactive mAbs revealed that their unmutated ancestors are specific for the endemic OC43 or HKU1 viruses and acquired enhanced affinity and breadth through somatic mutations. These data demonstrate that conserved epitopes in the coronavirus fusion machinery can be targeted by protective antibodies and provide a framework for structure-guided design of pan-{beta}-coronavirus vaccines eliciting broad protection.
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The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha). In vitro, B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N-terminal domain (NTD), in particular to the clinically approved bamlavinimab and imdevimab monoclonal antibodies. B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems as compared to B.1.1.7, associated with B.1.617.2 spike being in a predominantly cleaved state compared to B.1.1.7. Additionally we observed that B.1.617.2 had higher replication and spike mediated entry as compared to B.1.617.1, potentially explaining B.1.617.2 dominance. In an analysis of over 130 SARS-CoV-2 infected healthcare workers across three centres in India during a period of mixed lineage circulation, we observed substantially reduced ChAdOx-1 vaccine efficacy against B.1.617.2 relative to non-B.1.617.2. Compromised vaccine efficacy against the highly fit and immune evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.
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SARS-CoV-2 entry is mediated by the spike (S) glycoprotein which contains the receptor-binding domain (RBD) and the N-terminal domain (NTD) as the two main targets of neutralizing antibodies (Abs). A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429) was originally detected in California and is currently spreading throughout the US and 29 additional countries. It is unclear whether antibody responses to SARS-CoV-2 infection or to the prototypic Wuhan-1 isolate-based vaccines will be impacted by the three B.1.427/B.1.429 S mutations: S13I, W152C and L452R. Here, we assessed neutralizing Ab responses following natural infection or mRNA vaccination using pseudoviruses expressing the wildtype or the B.1.427/B.1.429 S protein. Plasma from vaccinated or convalescent individuals exhibited neutralizing titers, which were reduced 3-6 fold against the B.1.427/B.1.429 variant relative to wildtype pseudoviruses. The RBD L452R mutation reduced or abolished neutralizing activity of 14 out of 35 RBD-specific monoclonal antibodies (mAbs), including three clinical-stage mAbs. Furthermore, we observed a complete loss of B.1.427/B.1.429 neutralization for a panel of mAbs targeting the N-terminal domain due to a large structural rearrangement of the NTD antigenic supersite involving an S13I-mediated shift of the signal peptide cleavage site. These data warrant closer monitoring of signal peptide variants and their involvement in immune evasion and show that Abs directed to the NTD impose a selection pressure driving SARS-CoV-2 viral evolution through conventional and unconventional escape mechanisms.
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Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant now seen in 50 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses following vaccination with mRNA-based vaccine BNT162b2. We measured neutralising antibody responses following a single immunization using pseudoviruses expressing the wild-type Spike protein or the 8 amino acid mutations found in the B.1.1.7 spike protein. The vaccine sera exhibited a broad range of neutralising titres against the wild-type pseudoviruses that were modestly reduced against B.1.1.7 variant. This reduction was also evident in sera from some convalescent patients. Decreased B.1.1.7 neutralisation was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the Receptor Binding Motif (RBM) (5 out of 31), but not in neutralising mAbs binding outside the RBM. Introduction of the E484K mutation in a B.1.1.7 background to reflect newly emerging viruses in the UK led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone. E484K emergence on a B.1.1.7 background represents a threat to the vaccine BNT162b.
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Systems composed of bioadhesive and thermoresponsive polymers can combine in situ gelation with bio/mucoadhesion, enhancing retention of topically applied drugs. The effect of bioadhesive sodium carboxymethylcellulose (NaCMC) and hydroxypropyl methylcellulose cellulose (HPMC) on the properties of thermoresponsive Pluronic® F127 (F127) was explored, including micellization and the mucoadhesion. A computational analysis between these polymers and their molecular interactions were also studied, rationalising the design of improved binary polymeric systems for pharmaceutical and biomedical applications. The morphological characterization of polymeric systems was conducted by SEM. DSC analysis was used to investigate the crystallization and micellization enthalpy of F127 and the mixed systems. Micelle size measurements and TEM micrographs allowed for investigation into the interference of cellulose derivatives on F127 micellization. Both cellulose derivatives reduced the critical micellar concentration and enthalpy of micellization of F127, altering hydrodynamic diameters of the aggregates. Mucoadhesion performance was useful to select the best systems for mucosal application. The systems composed of 17.5% (w/w) F127 and 3% (w/w) HPMC or 1% (w/w) NaCMC are promising as topical drug delivery systems, mainly on mucosal surfaces. They were biocompatible when tested against Artemia salina, and also able to release a model of hydrophilic drug in a controlled manner.
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Micelas , Poloxâmero , Derivados da Hipromelose , Metilcelulose , ReologiaRESUMO
Acacia mearnsii gum is not commercially exploited, being characterized as residue from A. mearnsii cultivation. This work investigated the A. mearnsii gum polysaccharide composition, its cytotoxicity and the technological effect as a stabilizer in ice cream. A. mearnsii gum showed a similar chemical structure to commercial gum Arabic and did not decrease the viability and proliferation of fibroblast cells (Balb/3T3) and hepatocarcinoma (HepG2). Rheological tests showed that the ice cream stabilized by the A. mearnsii gum had a more structured system (more interactions between the mixture components) and the same melting characteristics as the ice cream samples made with commercial gum Arabic. The results showed that A. mearnsii gum, which is actually an agro-industrial residue from tannin production for industry, is a potential stabilizing gum for the food industry, contributing to the economic development of the exploitation chain of A. mearnsii products and by-products.
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Acacia/química , Sorvetes , Gomas Vegetais/química , Polissacarídeos/análise , Animais , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Goma Arábica/química , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética , Camundongos Endogâmicos BALB C , Gomas Vegetais/análise , Gomas Vegetais/toxicidade , Polissacarídeos/química , ReologiaRESUMO
SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is the most divergent region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent RBM variant, N439K. We demonstrate that N439K S protein has enhanced binding affinity to the hACE2 receptor, and that N439K virus has similar clinical outcomes and in vitro replication fitness as compared to wild- type. We observed that the N439K mutation resulted in immune escape from a panel of neutralizing monoclonal antibodies, including one in clinical trials, as well as from polyclonal sera from a sizeable fraction of persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.
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Poloxamer 407 (polox407) is widely studied as thermogelling polymer, transitioning to a gel state when warmed Polox407 forms weak hydrogels with rapid dissolution in excess solvent. This study reports the development of binary systems composed of polox407 and hydroxypropyl methylcellulose (HPMC) or sodium carboxymethylcellulose (NaCMC) aiming to improve the rheological and mechanical properties of the hydrogel. The interaction between polox407 and cellulose derivatives was studied, and their interaction with biological surfaces predicted. The carbohydrates affected the mechanical and rheological behavior of polox407 in different ways, dependent on polymer type, concentration, and temperature. Tsol/gel and rheological interaction parameters were useful to select the most suitable formulations for topical or local application. Most of the binary systems exhibited plastic behavior, thixotropy and viscoelastic properties. Appropriate formulations were identified for local application, such as 17.5/3; 17.5/4; 20/3 and 20/4 (%, w/w) for polox407/HPMC; and 17.5/1; 17.5/1.5; 20/1 and 20/1.5 (%, w/w) for polox407/NaCMC.
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Carboximetilcelulose Sódica/química , Hidrogéis/química , Derivados da Hipromelose/química , Poloxâmero/química , Adesividade , Elasticidade , Reologia , TemperaturaRESUMO
Mucoadhesive nanostructured systems comprising poloxamer 407 and Carbopol 974P® have already demonstrated good mucoadhesion, as well as improved mechanical and rheological properties. Curcumin displays excellent biological activity, mainly in oral squamous cancer; however, its physicochemical characteristics hinder its application. Therefore, the aim of this study was to develop nanostructured formulations containing curcumin for oral cancer therapy. The photophysical interactions between curcumin and the formulations were elucidated by incorporation kinetics and location studies. They revealed that the drug was quickly incorporated and located in the hydrophobic portion of nanometer-sized polymeric micelles. Moreover, the systems displayed plastic behavior with rheopexy characteristics at 37 °C, viscoelastic properties and a gelation temperature of 36 °C, which ensures increased retention after application in the oral cavity. The mucoadhesion results confirmed the previous findings with the nanostructured systems showing a residence time of 20 min in porcine oral mucosa under flow system conditions. Curcumin was released after 8 h and could permeate through the porcine oral mucosa. Cytotoxicity testing revealed that the formulations were selective to cancer cells over healthy cells. Therefore, these systems could improve the physicochemical characteristics of curcumin by providing improved release and permeation, while selectivity targeting cancer cells.