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

Intercalation of sulfonate into layered double hydroxide: Comparison of simulation with experiment

We perform computational modeling studies to explore the properties of functionalized Mg-Al layered double hydroxides (LDHs). Using molecular dynamics (MD) simulations we study the intercalation of C8H17SO3 -sulfonate into a Mg:Al 2:1 LDH system for which the experimental data have recently been reported (J.Phys. Chem.C 2007, 111, 4021). An ab initio force field (condensed-phase optimized molecular potentials for atomistic simulation studies, COMPASS) is used for the MD simulations of the hybrid organic-inorganic system. Quantum mechanical density functional theory is also employed in order to establish structural and spectroscopic benchmarks for the sulfonate as a means of testing the force field. The interlayer structure, arrangement, and orientation of the intercalated species are examined and contrasted with the geometry of the isolated sulfonate. The self-diffusion coefficients of both the interlayer sulfonate and water are estimated to be 2.05 × 10-7 and 3.07 × 10-7 cm2/s at 300 K on the basis of 500 ps MD simulations. Computed powder X-ray diffraction patterns are in good accord with experiment. Computed infrared spectra are comparable with experiment in terms of line positions, while line intensities show room for improvement

Computer modeling study for intercalation of drug heparin into layered double hydroxide

We have performed computational modeling studies to explore the properties of functionalized Mg-Al layered double hydroxides (LDHs) for drug (heparin) delivery applications. Using molecular dynamics (MD) simulations, we investigated the intercalation of heparin into a Mg:Al 2:1 LDH system, for which some limited experimental data have been reported (Gu, Z. Chem. Mater. 2008, 20, 3715). Counterions and explicit water molecules have been included in order to simulate the experimental conditions performed for the related hybrid LDH systems. An ab initio force field (Condensed-phase Optimized Molecular Potentials for Atomistic Simulation Studies: COMPASS) was used for the MD simulations of the hybrid organic-inorganic systems. The interlayer structure, arrangement, and orientation of the intercalated species were examined and contrasted with the geometry of the isolated systems. The close contacts and hydrogen bonds between drug heparin and its surroundings in the hybrid system were analyzed, and the self-diffusion coefficients of both heparin and water molecules were estimated to be 5.6 x 10(-9) cm(2)/s and 8.5 x 10(-8) cm(2)/s at 300 K on the basis of 2 ns MD simulations. Implications for the stability of the hybrid LDH-drug systems were also discussed. Computed powder X-ray diffraction patterns were compared with those of related LDH-drug experiments