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.

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.

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.

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.

Emulgels Containing Propolis and Curcumin: The Effect of Type of Vegetable Oil, Poly(Acrylic Acid) and Bioactive Agent on Physicochemical Stability, Mechanical and Rheological Properties.

Emulgels are obtained by the entrapment of an organic phase within a three-dimensional network built by hydrophilic molecules. Polymers based on cross-linked poly(acrylic acid) have been utilized as gel matrices, improving adhesiveness, rheological and mechanical performance. Propolis (PRP) produced by Apis mellifera L. bees displays a wide range of biological activities. Together with curcumin (CUR), they may show synergic anti-inflammatory, antioxidant and antimicrobial action on skin disorders. This work investigated the effect of vegetable oils (sweet almond, andiroba, and passion fruit) with regard to the physicochemical properties of emulgels composed of Carbopol 934P®, Carbopol 974P®, or polycarbophil aiming the CUR and PRP delivery. Physicochemical stability enabled the selection of systems containing passion fruit or andiroba oil. Mechanical and rheological characteristics provided rational comprehension of how vegetable oils and bioactive agents affect the structure of emulsion gels. All formulations exhibited high physiochemical stability and properties dependent on the polymer type, oil, and bioactive agent. Formulations displayed pseudoplastic, thixotropic and viscoelastic properties. Emulgels containing andiroba oil were the most stable systems. Carbopol 934P® or polycarbophil presence resulted in formulations with improved smoothness and mechanical properties. Systems containing andiroba oil and one of these two polymers are promising for further investigations as topical delivery systems of CUR and/or PRP on the skin and mucous membranes.

Design of Mucoadhesive Strips for Buccal Fast Release of Tramadol.

Tramadol hydrochloride is a synthetic analogue of codeine and shows activity on the central nervous system as an opioid agonist and inhibitor of serotonin and norepinephrine reuptake. It has been used for controlling moderate to severe pain. Mucoadhesive fast-dissolving films can present greater drug availability and patient acceptance when compared to the systems of peroral administration. The films were prepared using the solvent casting method with ethylcellulose, polyvinylpyrrolidone and poly(vinyl alcohol). The effect of each polymer concentration was investigated using a 2³ factorial design with repetition at the central point. The formulations were subjected to physicochemical, mechanical, ex vivo mucoadhesive and in vitro drug release profile analysis. These properties were dependent on the polymeric composition (independent factors) of each system. The optimized formulations showed good macroscopic characteristics, improved resistance to bending, rigidity, rapid swelling up to 60 s, improved mechanical and mucoadhesive characteristics, and also fast dissolving and tramadol release. The optimized formulations constitute platforms and strategies to improve the therapy of tramadol with regard to availability at the site of application, considering the necessity of rapid pain relief, and show potential for in vivo evaluation.

Mucoadhesive polymeric films comprising polyvinyl alcohol, polyvinylpyrrolidone, and poloxamer 407 for pharmaceutical applications.

Polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) have been extensively studied for their use in film formation. Poloxamer 407 (P407) is a block copolymer that has thermo-responsive and surfactant properties when used in pharmaceutical systems. These polymers are already used in liquid or semi-solid systems for ocular and parenteral drug delivery. However, the effect of P407 presence in solid pharmaceutical films composed of different PVA:PVP ratios have not been investigated yet. Therefore, this work investigated the influence of P407 added to the binary polymer mixture of PVA and PVP for the development of solid films aiming for pharmaceutical applications. The rheological properties of dispersions were investigated, and films were prepared by solvent casting method using different P407:PVA:PVP ratios according to a factorial design 23 (plus center point). The mechanical and in vitro mucoadhesive properties of films, as well as the disintegration time were investigated. Systems presented high mechanical resistance, mucoadhesion, and disintegration timeless than 180 s. It was found that higher concentrations of PVA increase mechanical properties and decrease disintegration time, and higher proportions of PVP and P407 increased mucoadhesion. The films could be classified as fast disintegrating films and represent a promising alternative for modifying drug delivery and pharmaceutical applications.

Development and in vitro evaluation of buccal mucoadhesive films for photodynamic inactivation of Candida albicans.

Candidiasis is one of the most common diseases that occur in the oral cavity, caused mainly by the species Candida albicans. Methylene blue (MB) has a potential for microbial photoinactivation and can cause the destruction of fungi when applied in Photodynamic Therapy (PDT). Mucoadhesive films are increasingly being studied as a platform for drug application due to their advantages when compared to other pharmaceutical forms. The aim of this work was to develop mucoadhesive buccal film containing poloxamer 407 (P407), alcohol polyvinyl (PVA) and polyvinylpyrrolidone (PVP) for the release of MB aiming the photoinactivation of Candida albicans in buccal infections. Different amounts of P407 were added to the binary polymeric blends composed PVA and PVP. Formulations were characterized as morphology, thickness, density, bending strength, mechanical properties, water vapor transmission, disintegration time, mucoadhesion, DSC, ATR-FTIR, in vitro drug release profile and photodynamic inactivation. The films displayed physicochemical characteristics dependent of polymeric composition, mucoadhesive properties, fast MB release and were effective in photo inactivate the local growth of Candida albicans isolates. The formulation containing the lowest PVA and P407 amounts displayed the best performance. Therefore, data obtained from the film system show its potentially useful role as a platform for buccal MB delivery in photoinactivation of C. albicans, showing its potential for in vivo evaluation.

Emulgels Containing Carbopol 934P and Different Vegetable Oils for Topical Propolis Delivery: Bioadhesion, Drug Release Profile, and Ex Vivo Skin Permeation Studies.

Topical administration can enable a more efficient therapy based on the improved bioavailability and patient compliance. Wounds and infections can lead to modifications of skin physiology and body protective function. Propolis (PRP) is utilized for skin protection and treatment. However, PRP extracts do not show suitable rheological characteristics and can cause irritation, pain, ulceration, and healing difficulties when they are administered on the harmed skin. Emulgels composed of Carbopol 934P (C934P) and different vegetable oils have been proposed for propolis extract release and may be a good strategy for topical delivery. The aim of this study was to investigate the bioadhesive properties, PRP release profile, skin permeation, and retention, by Franz's diffusion cell and photoacoustic spectroscopy (PS), of these emulgels. Formulations were composed of C934P and passion fruit oil (PF), sweet almond oil (SA), or andiroba oil (AO). PRP or by-product extracts were added to the systems, drug release profile was investigated, and porcine ear skin was utilized for analyses of bioadhesive properties, skin permeation, and retention. All formulations displayed similar bioadhesive force (0.05-0.07 N); PRP release was modified (prolonged), dependent on formulation composition, and mainly governed by diffusion. PS and analysis using diffusion cell showed that the systems could provide dermal permeation and retention, which was more effective for formulations containing AO. Considering the importance of propolis for many skin therapies, the emulgels containing AO for PRP delivery are worthy of biological studies and further clinical evaluation.

Technological development of mucoadhesive film containing poloxamer 407, polyvinyl alcohol and polyvinylpyrrolidone for buccal metronidazole delivery.

Aim: This work aimed to develop a mucoadhesive film composed of a triblock copolymer (poloxamer 407), polyvinyl alcohol and polyvinylpyrrolidone for buccal modified delivery of metronidazole. Materials & methods: Three film formulations containing different polymer amounts were prepared by solvent casting. They were characterized as physicochemical, mechanical and mucoadhesive properties, and in vitro metronidazole release profiles. Results: Films displayed physicochemical, mechanical and mucoadhesive characteristics dependent of polymeric composition and drug presence. They could rapidly swell and promote the fast drug release (80% in 20 min) that was governed by Fickian diffusion. The films showed total disintegration in less than 90 s and total drug release in 30 min. Conclusion: Therefore, the formulations represent a promising alternative for modifying of buccal metronidazole delivery for pharmaceutical applications.