Photodynamic therapy (PDT) is a light-activated chemical reaction used for the selective destruction of tissue. For this, various colorants may be applied, such as erythrosine (ERI), a dye already approved by the Food and Drug Administration (FDA) for various purposes. Although promising for PDT, ERI has a high hydrophilic profile that impacts its activity. To solve this, the combination of ERI with thermoresponsive and bioadhesive polymers may prove effective. Bio/mucoadhesive and thermoresponsive systems have attracted increasing interest in the development of novel pharmaceutical formulations for topical applications due to their ability to improve adhesion to the mucosa and prolong the residence time at the application site. In this study, systems based on poloxamer 407 (P407) in combination with cellulose derivatives (HPMC and NaCMC) were optimized, aiming at the topical release of ERI for PDT. The results demonstrated that the formulations containing low concentrations of cellulose derivatives exhibited greater adhesiveness and consistency at physiological temperature (37 °C), favoring the maintenance of the system at the application site. Regarding the gelation temperature (Tsol/gel), the formulations displayed values close to body temperature. The formulations with NaCMC showed a slightly higher Tsol/gel compared to HPMC ones, but it was adjustable by the polymer concentration. The addition of ERI influenced the mechanical and adhesive properties of the systems. In formulations containing HPMC, high concentrations of ERI increased bio/mucoadhesiveness, while in systems with NaCMC, the presence of ERI reduced this property. In both cases, the formulations maintained high consistency at 37 °C, contributing to the control of the active release at the application site. Rheological analysis revealed non-Newtonian behavior in all formulations, with greater consistency and elasticity at high temperatures. P407 was mainly responsible for the thermoresponsive transition from sol to gel, conferring desirable characteristics for topical application. Photodynamic activity was relevant in both formulations containing NaCMC and HPMC, which demonstrated greater capacity for degrading uric acid under light exposure. These systems are promising for the controlled release of drugs in photodynamic therapy, providing prolonged retention in the target tissue and maximizing the therapeutic efficacy of ERI.

This study investigated polymeric blends of cellulose derivatives and poloxamer 407 as thermoresponsive and bioadhesive systems for drug delivery, with focus on the topical administration of quercetin. A preparation method was optimized and the physicochemical, mechanical, rheological (flow and viscoelasticity), and bioadhesive properties of systems containing poloxamer 407 and either sodium carboxymethylcellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) were evaluated. The formulations showed an increase in textural properties and softness index with the quercetin presence, type of cellulose derivative and the increase in temperature from 25 to 34 C-degrees (p < 0.05). The formulations displayed pseudoplastic flow behavior, and the consistency index increased with the presence of quercetin and the temperature increase (p < 0.05). Thixotropy was observed for formulations containing quercetin at 34( degrees)C. The drug presence improved the viscoelastic properties of systems, but the effect of the increase of its concentration was not significant (p > 0.05). The incorporation of quercetin led to an increase progressively in ex-vivo bioadhesiveness with the increase in the concentration of quercetin in systems. The formulations composed of P407 and NaCMC (F1-Q2 and F1-Q4) displayed improved mechanical, rheological and bioadhesive properties for topical administration of quercetin, being promising for biomedical and pharmaceutical applications.

The complexity of treating neurological diseases has meant that new strategies have had to be developed to deliver drugs to the brain more efficiently and safely. Intranasal drug delivery is characterized by its ease of administration, safety, and rapid delivery directly from the nose to the brain. Several strategies have been developed to improve the delivery of drugs to the brain via nasal administration. These include the use of mucoadhesive and thermoresponsive polymers and their combination into polymer blends, as well as the use of liposomes, niosomes, and nano- and microemulsions. Therefore, this review focuses on technologies for developing pharmaceutical systems aimed at delivery via the nose to the brain, contributing to new treatments for difficult neurological disorders. Some of the most common and difficult-to-treat neurological conditions, the intranasal route of administration, and the anatomy of the nasal cavity have been discussed, as well as factors that may influence the absorption of drugs administered into the nose. The types of intranasal formulations and the devices that can be used to administer these products are also discussed in this review. Strategies for improving the transport of bioactive agents and increasing bioavailability are highlighted. The technologies discussed in this review can facilitate the development of formulations with improved properties, such as drug release and mucoadhesiveness, which have several advantages for patients requiring complex neurological treatments.

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 degree celsius and pseudoplastic with a yield value at 37 degree celsius, 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.

New pharmaceutical formulations have been proposed as strategies to improve transport and provide best conditions to control the drug release rate in specific biological environments, such as mucosa surfaces. Herein, formulations containing binary systems Poloxamer (PL) 407 15 % and PL 338 15 %, combined with hyaluronic acid, carrying the local anesthetic bupivacaine (BVC), were studied by molecular dynamics, while other structural parameters were determined by Dynamic Light Scattering for stablishing relationships with mucoadhesive properties and cytotoxicity evaluation. The binary system PL 407 15 %/PL 338 15 % exhibited a well -organized structural morphology, with more hydrated corona, and increased mucoadhesive properties over mucin layers. After hyaluronic acid (HA) incorporation, it was observed an increase on the force of detachment, possibly due to HA role as a linker among mucin layers independently of PL supramolecular structures. On the other hand, the addition of BVC or HA/BVC into the binary system decreased the force of detachment, as a response of augmented of compactness of these hydrogels caused by desolvation of PO core, showing the influence of all components and their chemical interactions into the structural organization and their biopharmaceutical performance relationships.

The use of foods to color other foods (coloring food) should be considered in food production. In this study, freeze-dried canistel (Pouteria campechiana (Kunth) Baehni) pulp underwent a photostability test. A blue LED light with a maximum intensity of 420 nm was utilized to induce photodegradation of the pulp. After irradiation, the samples were analyzed using photoacoustic spectroscopy. Different concentrations (2

Summary Aqueous extract rich in phenolic compounds and carbohydrates obtained as a co‐product during the trub‐debittering process can be used as a new sustainable ingredient to improve food quality properties. This water‐soluble extract (WE) was used for evaluating its own antioxidant capacity when added to processed cheese at up to 1.00% (w/w); and were also evaluated for total phenolic compounds, antioxidant activity, FTIR spectroscopy, lipid oxidation, oxidative stability, texture and rheological properties. WE addition increased the antioxidant activity of processed cheese by up to 88.40% and 81.90% for DPPH and ABTS, reduced the product lipid oxidation by up to 54.31% and showed greater oxidative stability (Rancimat) compared to the Control. Samples melting property was not changed, and samples with WE showed a more stable structure after melting. Use of WE showed that it can be used as natural antioxidant in processed cheese, improving its quality and texture properties.

The development of dermatological platforms capable of reducing the load of resistant microorganisms and accelerating healing is highly desirable. Thus, a topical micellar gel, composed of Carbopol (R), Pluronic (R) F127 and F68 polymers, Rose Bengal (Rb), and Copaifera reticulata Ducke oil-resin (CO) was developed as a phototherapeutic emulgel to fulfill this demand. Therefore, the system aimed to minimize the microbial load (by photodynamic therapy - PDT) and to accelerate the healing process (by Copaifera reticulata Ducke oil-resin activity). The emulgel showed a gelation temperature of 11.2 +/- 0.0 degrees C, which allows its phase transition after body temperature stimuli. Furthermore, the emulgel had thixotropic and viscoelasticity performance at body temperature, and drug skin permeation ability. Recently we presented the potential activity of the topical Rb-loaded thermosensitive gel, which can eliminate the microorganism load. Therefore, the properties of the multidrug topical emulgel presented in this work are advantageous and have microbicidal and healing potential to be explored for future in vitro and in vivo studies.

Microneedles (MN) constitute a technological strategy to break the skin barrier in a minimally invasive way. MN can enhance the availability of drugs in the deeper layers of the skin. Propolis (PROP) is a gum-resin produced by Apis mellifera L. bees and displays several properties like antioxidant and immunostimulating actions. PROP extracts are utilized on therapeutics, exhibiting disadvantages like unpleasant and strong taste, aromatic odor, high solvent concentration, problems of bioavailability. These result in difficulties for administration and pose challenges to the patient compliance to the therapeutics, showing the need for the development of improved systems for PROP delivery. Therefore, the aim of this work was to prepare and optimize MN composed of poloxamer 407, polyvinyl alcohol and polyvinylpyrrolidone, for controlled delivery of ethanolic or glycolic extract of PROP, and evaluate their biological properties. The optimization of MN formulations involved utilizing various PROP extracts and polymers, followed by the characterization of their hardness and in vitro drug release. Moreover, the formulations were evaluated for ex vivo skin permeation and in vitro generation of reactive oxygen species. As a result, MN containing PROP ethanolic extract displayed better structuring than those containing glycolic extract of PROP. The selected formulations presented quicker disintegration, which enabled the confirmation of the skin permeation of PROP extract in the epidermis and dermis. The optimized MN could produce reactive oxygen species and stimulate neutrophils and macrophages in vitro. In addition, they can be used as platforms for local administration of PROP, in order to enable the increased skin drug delivery, and provide antioxidant and immunostimulating action. Further studies are needed to evaluate these properties in vivo.

The environment can modify the physiology and body protective function of the skin. Propolis (PRP) and curcumin (CUR) possess important antioxidant and antimicrobial properties, and they can be administered in a combined way and using photodynamic therapy (PDT). Emulgels can control drug release due to the physicochemical properties of the gel and the emulsion. They constitute a good strategy for achieving an improved platform for the combined delivery of PRP and CUR. There are no other studies of emulgels composed of PRP and CUR and their performance as antimicrobial and skin healing using or not PDT. This study aimed to investigate the effect of Carbopol 934 P (C934P), 974 P (C974P) or polycarbophil (PC) on physicochemical stability, antioxidant activity, drug release profile, antimicrobial activity, and ex vivo skin permeation and retention of emulgels containing PRP and CUR. Formulations containing C974P or PC displayed improved stability and antioxidant activity. They displayed activity against Staphylococcus aureus and modified (extended) drug release, governed mainly by non-Fickian anomalous transport. C974P and PC resulted in improved emulgels for combined CUR and PRP delivery, allowing the drugs to cross the stratum corneum, and permeate the epidermis, reaching the dermis. The selected emulgels are candidates for further studies to prove their action and benefits to skin health.

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.

Thermosensitive bioadhesive formulations can display increased retention time, skin permeation, and improve the topical therapy of many drugs. Acne is an inflammatory process triggered by several factors like the proliferation of the bacteria Propionibacterium acnes. Aiming for a new alternative treatment with a natural source, propolis displays great potential due to its antibiotic, anti-inflammatory, and healing properties. This study describes the development of bioadhesive thermoresponsive platform with cellulose derivatives and poloxamer 407 for propolis skin delivery. Propolis ethanolic extract (PES) was added to the formulations with sodium carboxymethylcellulose (CMC) or hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (Polox). The formulations were characterized as rheology, bioadhesion, and mechanical analysis. The selected formulations were investigated as in vitro propolis release, cytotoxicity, ex vivo skin permeation by Fourier Transform Infrared Photoacoustic Spectroscopy, and the activity against P. acnes. Formulations showed suitable sol-gel transition temperature, shear-thinning behavior, and texture profile. CMC presence decreased the cohesiveness and adhesiveness of formulations. Polox/HPMC/PES system displayed less cytotoxicity, modified propolis release governed by anomalous transport, skin permeation, and activity against P. acnes. These results indicate important advantages in the topical treatment of acne and suggest a potential formulation for clinical evaluation.

Cutaneous leishmaniasis (CL) is a neglected endemic disease that causes significant damage to the skin and upper respiratory mucosa. Topical treatments are a promising alternative, but the low permeation of the drugs is a huge medical challenge. Herein, a chemometric design approach leads to an innovative thermal stimuli-responsive emulsion-filled gel (SR-EFG) as a proposed medical therapeutic. Several combinations of the Pluronic (R) F127, Carbopol C934P (R), and high Copaifera reticulata Ducke oil-resin levels allowed the obtention of optimized delivery systems. The SR-EFG were mechanic and rheologically robust and had interfacial layer properties that allowed physicochemical stability. Human skin and SR-EFG contact proved bioadhesive effect and marked ability for SR-EFG to act as a permeation enhancer. The oil-resin-carried micelles reached deep layers of the human skin and had droplet size-dependent permeation properties. The validation of the medicinal ensured the composition stability by two years. The antiproliferative activity for Leishmania amazonensis and Leishmania infantum promastigotes ensured the drug's effectiveness, with IC50 (50% parasite inhibitory concentration) values equivalent to the effect of the non-formulated oil-resin. These characteristics consolidated the SR-EFG as a promising and innovative phytotherapeutic treatment proposal for CL and wound healing. (C) 2022 Elsevier B.V. All rights reserved.

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.

The use of products containing natural and sustainable substances has shown a remarkable growth in the pharmaceutical and cosmetic market, such as in the compounding pharmacy. This research aimed to develop, characterize, and evaluate the cutaneous bioengineering of natural and sustainable emulsions, providing a vehicle base for topical preparations. Nine O/W emulsions were developed changing the nonionic self-emulsifying wax (Cetearyl Olivate (and) Sorbitan Olivate, Cetearyl Glucoside (and) Cetearyl Alcohol, Candelilla/Jojoba/Rice Bran Polyglyceryl-3 Esters (and) Glyceryl Stearate (and) Cetearyl Alcohol (and) Sodium Stearoyl Lactylate), with or without the anionic co-emulsifier (Sodium Stearoyl Glutamate). They were characterized through preliminary stability tests, rheology and accelerated physicochemical stability study. Four formulations were approved (FB1, FB2, FB3 and FB5), but only FB1 (Cetearyl Olivate (and) Sorbitan Olivate with Sodium Stearoyl Glutamate) was considered stable, being selected for preservative efficacy evaluation and the cutaneous bioengineering. The hydration and transepidermal water loss (TEWL) of stratum corneum were analyzed comparing with a conventional topical vehicle (Emulsifying Wax NF). The clinical study showed that FB1 improved the skin hydration with no significant changes for TEWL, but demonstrated considered values. The FB1 could be classified as “skin friendly” and represents a promising natural and sustainable vehicle in compounded pharmacy preparations.

Microneedles (MNs) are a means to break the protective skin barrier in a minimally invasive way. By creating temporary micropores, they make biologically active agents available in the skin layers. Propolis (PRP) is a gum resin with a complex chemical composition, produced by bees Apis mellifera L. and showing several therapeutic properties (i.e., antibacterial, antiviral, antifungal, anti-inflammatory, healing, and immunomodulatory properties). The administration of PRP extracts by conventional routes has some disadvantages, such as running off over the skin in liquid or emulsion form. When taken orally, the extracts have a strong and unpleasant taste. The aim of this work was to fabricate and characterize microneedles containing polyvinyl alcohol, polyvinylpyrrolidone, poloxamer P407, and an ethanolic or glycolic extract of PRP. Also, the obtained structures were microscopically and mechanically characterized. The results of the mechanical analysis showed that formulations containing 3% of P407 presented the highest compression values in a hard surface, which was also confirmed by the height and base values of the morphological analysis and by the microscopy images. It was possible to design MNs and select the best formulations for future tests. MNs containing an ethanolic extract of PRP showed to be better structured than MNs containing a glycolic extract of PRP. The MNs obtained in these studies proved to be a promising platform for the topical application of PRP.

In this study, we developed a bioadhesive emulsion-filled gel containing a high amount of Copaifera reticulata Ducke oil-resin as a veterinary or human clinical proposal. The phytotherapeutic system had easy preparation, low cost, satisfactory healing ability, and fly repellency, making it a cost-effective clinical strategy for wound care and myiasis prevention. Mechanical, rheological, morphological, and physical stability assessments were performed. The results highlight the crosslinked nature of the gelling agent, with three-dimensional channel networks stabilizing the Copaifera reticulata Ducke oil-resin (CrD-Ore). The emulgel presented antimicrobial activity, satisfactory adhesion, hardness, cohesiveness, and viscosity profiles, ensuring the easy spreading of the formulation. Considering dermatological application, the oscillatory responses showed a viscoelastic performance that ensures emulgel retention at the action site, reducing the dosage frequencies. In Vivo evaluations were performed using a case report to treat ulcerative skin wounds aggravated by myiasis in calves and heifers, which demonstrated healing, anti-inflammatory, and repellent performance for the emulsion-filled gel. The emulgel preparation, which is low in cost, shows promise as a drug for wound therapy.

Graft copolymers with brush-type architectures are explored containing poly(ethylene glycol) methacrylates copolymerized with "thermoresponsive" monomers which impart lower critical solution temperatures to the polymer. Initially, the chemical structure of the thermoresponsive polymer is explored, synthesizing materials containing N-isopropyl acrylamide, N,N-diethyl acrylamide and diethylene glycol methyl ether methacrylate. Thermoresponsive graft-copolymers containing di(ethylene glycol) methyl ether methacrylate (DEGMA) exhibited phase transition temperature close to physiological conditions (ca 30 degrees C). The effect of polymer composition was explored, including molecular weight, PEG-methacrylate (PEGMA) terminal functionality and PEGMA/DEGMA ratios. Molecular weight exhibited complex relationships with phase behavior, where lower molecular weight systems appeared more stable above lower critical solution temperatures (LCST), but a lower limit was identified. PEGMA/DEGMA feed was able to control transition temperature, with higher PEGMA ratios elevating thermal transition. It was found that PEGMA terminated with methoxy functionality formed stable colloidal structures above LCST, whereas those the hydroxy termini generally formed two-phase sedimented systems when heated. Two thermoresponsive DEGMA-based graft polymers, poly(PEGMA(7)-ran-DEGMA(170)) and poly(PEGMA(1)-ran-DEGMA(38)), gave interesting temperature-dependent rheology, transitioning to a viscous state upon heating. These materials may find application in forming thermothickening systems which modify rheology upon exposure to the body's heat. (C) 2021 The Authors. Published by Elsevier B.V.

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.