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.

A critical review about methodologies for the analysis of mucoadhesive properties of drug delivery systems.

Mucoadhesion is a useful strategy for drug delivery systems, such as tablets, patches, gels, liposomes, micro/nanoparticles, nanosuspensions, microemulsions and colloidal dispersions. Moreover, it has contributed to many benefits like increased residence time at application sites, drug protection, increased drug permeation and improved drug availability. In this context, investigation into the mucoadhesive properties of pharmaceutical dosage forms is fundamental, in order to characterize, understand and simulate the in vivo interaction between the formulation and the biological substrate, contributing to the development of new mucoadhesive systems with effectiveness, safety and quality. There are a lot of in vivo, in vitro and ex vivo methods for the evaluation of the mucoadhesive properties of drug delivery systems. However, there also is a lack of standardization of these techniques, which makes comparison between the results difficult. Therefore, this work aims to show an overview of the most commonly employed methods for mucoadhesion evaluation, relating them to different proposed systems and using artificial or natural mucosa from humans and animals.

The effect of erythrosine-B on the structuration of poloxamer 407 and cellulose derivative blends: In silico modelling supporting experimental studies.

Erythrosine is a dye approved for medical use that has shown promising photodynamic activity, allowing for the inactivation of microorganisms and activity against malignant cells. Despite the great photodynamic potential, erythrosine exhibits hydrophilicity, negatively impacting its action in biological membranes. Therefore, the incorporation of erythrosine in micellar polymeric systems, such as poloxamers, may overcome this limitation. Moreover, using bioadhesive and thermoresponsive polymers to combine in situ gelation and bioadhesion may enhance retention of this topically applied drug. In this work, mucoadhesive and thermoresponsive micellar systems were prepared containing erythrosine in two states: the native form (ERI) and the disodium salt (ERIs). The systems were evaluated based on the effect of ERI/ERIs on the micellar structure of the binary polymer mixtures. Optimised combinations of poloxamer 407 (polox407) and mucoadhesive sodium carboxymethylcellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) were used as micellar systems for ERI or ERIs delivery. The systems were studied with respect to theoretical interactions, qualitative composition, morphology, and micellar properties. In silico modelling indicated a higher interaction of the drug with poly(ethylene oxide) (PEO) than poly(propylene oxide) (PPO) fragments of polox407. Systems containing NaCMC displayed a repulsive effect in the presence of erythrosine, due to the polymer's charge density. Both systems could convert the photosensitizer in its monomeric form, ensuring photodynamic activity. In these mixtures, crystallinity, critical micellar temperature and enthalpy of polox407 micellisation were reduced, and micellar size, evaluated by transmission electron microscopy (TEM), showed low impact of ERI/ERIs in HPMC preparations. Aiming toward photodynamic applications, the findings showed how ERI or ERIs can affect the micellar formation of gels composed of 17.5% (w/w) polox407 and 3% (w/w) HPMC or 1% (w/w) NaCMC, important for understating their behaviour and future utilisation as erythrosine delivery systems.