Pharmaceutical applications and requirements of resins for printing by digital light processing (DLP).

The digital light processing (DLP) printer has proven to be effective in biomedical and pharmaceutical applications, as its printing method does not induce shear and a strong temperature on the resin. In addition, the DLP printer has good resolution and print quality, which makes it possible to print complex structures with a customized shape, being used for various purposes ranging from jewelry application to biomedical and pharmaceutical areas. The big disadvantage of DLP is the lack of a biocompatible and non-toxic resin on the market. To overcome this limitation, an ideal resin for biomedical and pharmaceutical use is needed. The resin must have appropriate properties, so that the desired format is printed when with a determined wavelength is applied. Thus, the aim of this work is to bring the basic characteristics of the resins used by this printing method and the minimum requirements to start printing by DLP for pharmaceutical and biomedical applications. The DLP method has proven to be effective in obtaining pharmaceutical devices such as drug delivery systems. Furthermore, this technology allows the printing of devices of ideal size, shape and dosage, providing the patient with personalized treatment.

Development of nanostructured environmentally responsive system containing hydroxypropyl methylcellulose for nose-to-brain administration of meloxicam.

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.

Development of Environmentally Responsive Self-Emulsifying System Containing Copaiba Oil-Resin for Leishmaniasis Oral Treatment.

Leishmaniasis is a disease caused by protozoa species of the Leishmania genus, and the current treatments face several difficulties and obstacles. Most anti-leishmanial drugs are administered intravenously, showing many side effects and drug resistance. The discovery of new anti-leishmanial compounds and the development of new pharmaceutical systems for more efficient and safer treatments are necessary. Copaiba oil-resin (CO) has been shown to be a promising natural compound against leishmaniasis. However, CO displays poor aqueous solubility and bioavailability. Self-emulsifying drug delivery systems (SEDDS) can provide platforms for release of hydrophobic compounds in the gastrointestinal tract, improving their aqueous solubilization, absorption and bioavailability. Therefore, the present work aimed to develop SEDDS containing CO and Soluplus® surfactant for the oral treatment of leishmaniasis. The design of the systems was accomplished using ternary phase diagrams. Emulsification and dispersion time tests were used to investigate the emulsification process in gastric and intestinal environments. The formulations were nanostructured and improved the CO solubilization. Their in vitro antiproliferative activity against promastigote forms of L. amazonensis and L. infantum, and low in vitro cytotoxicity against macrophages were also observed. More studies are necessary to determine effectiveness of SOL in these systems, which can be candidates for further pharmacokinetics and in vivo investigations.

In vitro antifungal activity of curcumin mediated by photodynamic therapy on Sporothrix brasiliensis.

BACKGROUND: Sporothrix brasiliensis is a pathogenic dimorphic fungus that affects humans and animals causing sporotrichosis. The treatment of this disease with conventional antifungals commonly results in therapeutic failures and resistance. Therefore, this study aimed to evaluate the in vitro effect of curcumin (CUR) mediated by photodynamic therapy (PDT) in its pure state and incorporated into pharmaceutical formulation in gel form, on the filamentous and yeast forms of S. brasiliensis. METHODS: Cells from both forms of the fungus were treated with pure curcumin (PDT-CUR). For this, CUR concentrations ranging from 0.09 to 50 µM were incubated for 15 min and then irradiated with blue LED at 15 J/cm². Similarly, it was performed with PDT-CUR-gel, at lower concentration with fungistatic action. After, a qualitative and quantitative (colony forming units (CFU)) analysis of the results was performed. Additionally, reactive oxygen species (ROS) were detected by flow cytometry. Results PDT with 0.78 µM of CUR caused a significant reduction (p < 0.05) in cells of the filamentous and yeast form, 1.38 log10 and 1.18 log10, respectively, in comparison with the control. From the concentration of 1.56 µM of CUR, there was a total reduction in the number of CFU (≥ 3 log10). The PDT-CUR-gel, in relation to its base without CUR, presented a significant reduction (p < 0.05) of 0.83 log10 for the filamentous form and for the yeast form, 0.72 log10. ROS release was detected after the PDT-CUR assay, showing that this may be an important pathway of death caused by photoinactivation. Conclusion PDT-CUR has an important in vitro antifungal action against S. brasiliensis strains in both morphologies.

Boosting the photodynamic activity of erythrosine B by using thermoresponsive and adhesive systems containing cellulose derivatives for topical delivery.

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.

Formulation and performance evaluation of emulgel platform for combined skin delivery of curcumin and propolis.

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.

Magnetic Gels in Skin Cancer Treatment: A Review of Potential Applications in Diagnostics, Drug Delivery and Hyperthermia.

Skin cancer (SC) is affecting an increasing number of people worldwide. Its lesions affect mainly the most exposed regions of the skin. SC is classified into to main categories: non-melanoma (basal cell carcinoma of the epidermis and squamous cell carcinoma) and melanoma (the abnormal proliferation of melanocytes, which is rarer, more hazardous, and more deadly). Prevention and early diagnosis are important actions, and surgery is often considered. After the removal of cancerous lesions, the local administration of medicine can guarantee anticancer therapeutic action, rapid healing and the recovery of tissue, ensuring the absence of recurrence. Magnetic gels (MGs) have attracted increased attention regarding their pharmaceutical and biomedical applications. They are magnetic nanoparticles (e.g., iron oxide nanoparticles) dispersed in a polymeric matrix, which constitute adaptive systems under a magnetic field. MGs can combine magnetic susceptibility, high elasticity, and softness, and are thus useful platforms for diagnostics, drug delivery, and also for hyperthermia. This manuscript reviews MGs as a technological strategy for the treatment of SC. An overview of SC and the treatment, types, and methods of preparing MGs are discussed. Moreover, the applications of MGs in SC and their future perspectives are considered. The combination of polymeric gels and magnetic nanoparticles continues to be investigated, and new products must hit the market. Clinical trials and new products are expected, due to the important advantages of MGs.

3D Printing as a Technological Strategy for the Personalized Treatment of Wound Healing.

Wound healing is a dynamic process which involves stages of hemostasis, inflammation, proliferation and remodeling. Any error in this process results in abnormal wound healing, generating financial burdens for health systems and even affecting the physical and mental health of the patient. Traditional dressings do not meet the complexities of ideal treatment in all types of wounds. For this reason, in the last decades, different materials for drug delivery and for the treatment of wounds have been proposed reaching novel level of standards, such as 3D printing techniques. The use of natural or synthetic polymers, and the correct design of these printed products loaded with cells and/or combined with active compounds, can generate an effective system for the treatment of wounds, improving the healing process and generating customized dressings according to the patient needs. This manuscript provides a comprehensive review of different types of 3D printing techniques, as well as its use in wound healing and its different stages, including the advantages and limitations of additive manufacturing and future perspectives.

Design as strategy for evaluation of the mechanical properties of binary mixtures composed of poly(methyl vinyl ether-alt-maleic anhydride) and Pluronic F127 for biomedical applications.

The synergism between thermoresponsive and bioadhesive polymers can lead to the optimization of materials with enhanced mechanical and bioadhesive properties. Quality by Design can assure the understanding and control of formulation variables. In this approach, Design of Experiment has been widely utilized as an important strategy. Poly(methyl vinyl ether-alt-maleic anhydride) (PVMMA) is a bioadhesive polymer and Pluronic F127 (PF127) shows thermoresponsiveness. The association of these two polymers has been poorly investigated. The aim of this work was to study the mechanical, bioadhesive and rheological properties of polymer mixtures composed of PVMMA and PF127, in order to select the best conditions and formulations for biomedical applications. Textural properties (hardness, compressibility, adhesiveness, cohesiveness and elasticity), softness index, bioadhesion and rheological characteristics (flow and viscoelasticity) showed that 17.5-20% (w/w) PF127-polymer mixtures displayed improved values of the parameters. However, the rheological interaction parameter showed low synergism, due to the polymers' characteristics and system organization. The formulations displayed gelation temperatures suitable for administration, with improved bioadhesive properties mainly at 34 °C and suggests the formulations can be used for biomedical applications. DoE constituted an important tool to investigate these systems showing the main effects that significantly influence the binary mixtures.

Microstructured Polymer System Containing Proanthocyanidin-Enriched Extract from Limonium brasiliense as a Prophylaxis Strategy to Prevent Recurrence of Porphyromonas gingivalis.

Periodontal diseases are a global oral health problem affecting almost 10% of the global population. Porphyromonas gingivalis is one of the main bacteria involved in the initiation and progression of inflammatory processes as a result of the action of the cysteine proteases lysin- and arginine-gingipain. Surelease/polycarbophil microparticles containing a lyophilized proanthocyanidin-enriched fraction from the rhizomes of Limonium brasiliense, traditionally named "baicuru" (ethyl acetate fraction), were manufactured. The ethyl acetate fraction was characterized by UHPLC by the presence of samarangenins A and B (12.10 ± 0.07 and 21.05 ± 0.44%, respectively) and epigallocatechin-3-O-gallate (13.44 ± 0.27%). Physiochemical aspects of Surelease/polycarbophil microparticles were characterized concerning particle size, zeta potential, entrapment efficiency, ethyl acetate fraction release, and mucoadhesion. Additionally, the presence of the ethyl acetate fraction-loaded microparticles was performed concerning potential influence on viability of human buccal KB cells, P. gingivalis adhesion to KB cells, gingipain activity, and P. gingivalis biofilm formation. In general, all Surelease/polycarbophil microparticles tested showed strong adhesion to porcine cheek mucosa (93.1 ± 4.2% in a 30-min test), associated with a prolonged release of the ethyl acetate fraction (up to 16.5 ± 0.8% in 24 h). Preincubation of KB cells with Surelease/polycarbophil microparticles (25 µg/mL) resulted in an up to 93 ± 2% reduced infection rate by P. gingivalis. Decreased activity of the P. gingivalis-specific virulence factors lysin- and arginine-gingipain proteases by Surelease/polycarbophil microparticles was confirmed. Surelease/polycarbophil microparticles decreased biofilm formation of P. gingivalis (97 ± 2% at 60 µg/mL). Results from this study prove the promising activity of Surelease/polycarbophil microparticles containing ethyl acetate fraction microparticles as a prophylaxis strategy to prevent the recurrence of P. gingivalis.

Applicability of an HPLC method for analysis of alcoholic and glycolic Brazilian green-propolis extracts

Abstract Brazilian green propolis has been widely used in food and pharmaceutical products due to its valuable source of phenolic compounds and versatile biological activities. The development and validation of analytical methods are extremely useful for the characterization and quality control of products containing propolis. Therefore, the aim of this study was to optimize, validate and investigate the applicability of a reversed-phase HPLC method for analysis of different types of Brazilian green propolis extracts (glycolic and ethanolic). The method showed to be selective for the propolis phenolic markers. The analysis of variance and residues demonstrated that the method had significant linear regression, without lack of fit. It was also a precise, accurate and robust method, which was of utmost importance to analyze both glycolic and ethanolic extracts and at different concentrations. Moreover, as these products can display most complex matrices to analyze, a valid HPLC method can also prove to be specific and versatile.

Photo-Phytotherapeutic Gel Composed of Copaifera reticulata, Chlorophylls, and k-Carrageenan: A New Perspective for Topical Healing.

Chronic wound healing represents an impactful financial burden on healthcare systems. In this context, the use of natural products as an alternative therapy reduces costs and maintains effectiveness. Phytotherapeutic gels applied in photodynamic therapy (PDT) have been developed to act as topical healing medicines and antibiotics. The bioactive system is composed of Spirulina sp. (source of chlorophylls) and Copaifera reticulata oil microdroplets, both incorporated into a polymeric blend constituted by kappa-carrageenan (k-car) and F127 copolymer, constituting a system in which all components are bioactive agents. The flow behavior and viscoelasticity of the formulations were investigated. The photodynamic activity was accessed from studies of the inactivation of Staphylococcus aureus bacteria, the main pathogen of hospital relevance. Furthermore, in vivo studies were conducted using eighteen rabbits with dermatitis (grade III and IV) in both paws. The gels showed significant antibiotic potential in vitro, eliminating up to 100% of S. aureus colonies in the presence or absence of light. The k-car reduced 41% of the viable cells; however, its benefits were enhanced by adding chlorophyll and copaiba oil. The animals treated with the phytotherapeutic medicine showed a reduction in lesion size, with healing and re-epithelialization verified in the histological analyses. The animals submitted to PDT displayed noticeable improvement, indicating this therapy's viability for ulcerative and infected wounds. This behavior was not observed in the iodine control treatment, which worsened the animals' condition. Therefore, gel formulations were a viable alternative for future pharmaceutical applications, aiming at topical healing.

Thermo and Photoresponsive Emulgel Loaded with Copaifera reticulata Ducke and Chlorophylls: Rheological, Mechanical, Photodynamic and Drug Delivery Properties in Human Skin.

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.

Design and Optimization of a Natural Medicine from Copaifera reticulata Ducke for Skin Wound Care.

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.

Mini-tablets as technological strategy for modified release of morphine sulfate.

This study aimed to use an intelligent formulation design for the development of mini-tablets for the modified release of morphine sulfate. A formulation (F1) was proposed using the Hiperstart® software. Based on the suggested formulation, two other formulations (F2 and F3) were prepared: one for modified and another for immediate drug release. The powders were characterized as bulk and tapped density, Hausner's factor, and compressibility index analyses. Mini-tablets were directly compressed and characterized by hardness, friability, size, and weight variation. The in vitro drug release profile was carried out according to apparatus 1 of USP. Formulations showed good flow properties, and the mini-tablets displayed characteristics according to the specified. In comparison to F3 (immediate release), F1 and F2 displayed slower drug release time, showing the efficiency of the matrix formed. F3 displayed 90% of drug released up to 10 min, while F1 and F2 required 240 min. The results highlight the importance to use intelligent formulation design for the development of improved mini-tablet matrices. Formulation F1 was found to be suitable for modified morphine sulfate release. Further studies with more formulations are necessary for the production of optimized mini-tablets with suitable prolonged morphine sulfate release.

Design and characterization of polymeric microneedles containing extracts of Brazilian green propolis.

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.

Self-Emulsifying Systems for Delivery of Bioactive Compounds from Natural Origin.

Nature has been used as therapeutic resources in the treatment of diseases for many years. However, some natural compounds have poor water solubility. Therefore, physicochemical strategies and technologies are necessary for development of systems for carrying these substances. The self-emulsifying drug delivery systems (SEDDS) have been used as carriers of hydrophobic compounds in order to increase the solubility and absorption, improving their bioavailability. SEDDS are constituted with a mixture of oils and surfactants which, when come into contact with an aqueous medium under mild agitation, can form emulsions. In the last years, a wide variety of self-emulsifying formulations containing bioactive compounds from natural origin has been developed. This review provides a comprehensive overview of the main excipients and natural bioactive compounds composing SEDDS. In addition, applications, new technologies and innovation are reviewed as well. Examples of self-emulsifying formulations administered in different sites are also considered for a better understanding of the use of this strategy to modify the delivery of compounds from natural origin.

Thermosensitive gel based on cellulose derivative for topical delivery of propolis in acne treatment.

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.

Drug Delivery Platforms Containing Thermoresponsive Polymers and Mucoadhesive Cellulose Derivatives: A Review of Patents.

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.

Design and Optimization of Stimuli-responsive Emulsion-filled Gel for Topical Delivery of Copaiba Oil-resin.

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.