Nanostructured lipid systems modified with waste material of propolis for wound healing: design, in vitro and in vivo evaluation

Propolis, a natural compound that can accelerate the wound healing process, is mainly used as ethanolic extract. The extractive solution may also be obtained from the propolis by-product (BP), transforming this waste material into a pharmaceutical active ingredient. Even if propolis does not show toxicity, when used as an extract over harmed skin or mucosa, the present ethanol content may be harmful to the tissue recovering, besides hindering the drug release. This study describes the development of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) as topical propolis delivery systems and the investigation of their in vitro and in vivo activities. The extracts were evaluated to guarantee their quality, and the lipid dispersions were characterized with respect to morphology (cryo-TEM), size and diffractometry (X-ray) properties. The occlusive capacity of formulations was also evaluated by an in vitro technique, which, determines the occlusion factor. The drug entrapment efficiency (EE), as well as the in vitro drug release profile from the nanoparticulate systems was investigated as well. The size analysis performed through 90 days was favorable to a topical administration and the polydispersity index, though not ideal in all cases due to the high content of resins and gums from the extracts, were relatively stable for the SLN. The propolis extract contributes to the occlusive potential of the formulations. The human immortalized keratinocytes presented good cell viability when tested with both extracts (propolis and BP) freely or entrapped in the systems. SLN modified with propolis material provided an acceleration of the in vivo wound healing process

Design of propolis-loaded film forming systems for topical administration: The effect of acrylic acid derivative polymers

In situ film forming systems are an alternative to the conventional dosage forms for topical application, performing superior contact and adhesiveness, with a consequent sustained and efficacious therapy. Propolis (PRP) is an extremely versatile natural compound due to its constitutive complexity and in terms of biological properties and uses as healing, anti-inflammatory, anti-cancer, antimicrobial, antiviral, and antifungal activities. In this work, the thermoresponsive polymer (poloxamer 407) and bioadhesive polymers derived fromthe acrylic acid were utilized to prepare dispersed systems containing different concentrations of propolis extract, and they were evaluated in terms of film forming capability. The gelation temperature and mechanical characteristics were also investigated so that some systems could be selected from a factorial design. The selected formulations presented good mechanical and rheological structuring properties, and they could incorporate the PRP extract. These systems denoted plastic flow behavior and viscoelasticity, and the PRP extract presence evinced greater capacity of the systems to support higher shear stress. When PRP extract was present, the systems with Carpobol 974P or polycarbophil (F7 and F10) presented greater structuring, with superior flexibility and rupture resistance. Moreover, they showed easiness for topical administration, with good spreadability and softness. Its excellent film forming capacity proved ex vivo, encourages further investigations for topical application

Thermal magnetic field activated propolis release from liquid crystalline system based on magnetic nanoparticles

Intra-periodontal pocket drug delivery systems, such as liquid crystalline systems, are widely utilized improving the drug release control and the therapy. Propolis is used in the treatment of periodontal diseases, reducing the inflammatory and infectious conditions. Iron oxide magnetic nanoparticles (MNPs) can improve the treatment when an alternating external magnetic field (AEMF) is applied, increasing the local temperature. The aim of this study was to develop a liquid crystalline system containing MNPs for intra-periodontal pocket propolis release. MNPs were prepared using iron salts and the morphological, size, thermal, x-ray diffraction, magnetometry and Mössbauer spectroscopy analyses were performed. Cytotoxicity studies using Artemia salina and fibroblasts were also accomplished. The systems were prepared using polyoxyethylene (10) oleyl ether, isopropyl myristate, purified water, and characterized by polarized optical microscopy, rheometry, and in vitro drug release profile using a periodontal pocket simulator apparatus. The antifungal activity of the systems was investigated against Candida yeasts using an AEMF. MNPs displayed nanometric size, were monodisperse and they displayed very low cytotoxicity. Microscopically homogeneous formulations were obtained displaying important physicochemical and biological properties. The system displayed prolonged release of propolis and important in vitro fungicide activity, which was increased when the AEMF was applied, indicating a potentially alternative therapy for the treatment of the periodontal disease