Reversible transformation of peptide assembly between densified-polysarcosine-driven kinetically and helix-orientation-driven thermodynamically stable morphologies.

Stimuli-responsive transformable biomaterials development can be manipulated practically by fine-tuning the built-in molecular design of their structural segments. Here, we demonstrate a peptide assembly by the bola-type amphiphilic polypeptide, glycolic acid-polysarcosine (PSar)13-b-(L-Leu-Aib)6-b-PSar13-glycolic acid (S13L12S13), which shows morphological transformations between hydrophilic chain-driven and hydrophobic unit-driven morphologies. The hydrophobic α-helical unit (L-Leu-Aib)6 precisely controls packing in the hydrophobic layer of the assembly and induces tubule formation. The densified, hydrophilic PSar chain on the assembly surface becomes slightly more hydrophobic as the temperature increases above 70 °C, starting to disturb the helix-helix interaction-driven formation of tubules. As a result, the S13L12S13 peptide assembly undergoes a reversible vesicle-nanotube transformation following a time course at room temperature and a heat treatment above 80 °C. Using membrane fluidity analysis with DPH and TMA-DPH and evaluating the environment surrounding the PSar side chain with NMR, we clarify that the vesicle was in a kinetically stable state driven by the dehydrated PSar chain, while the nanotube was in a thermodynamically stable state.

Design and characterization of highly porous curcumin loaded freeze-dried wafers for wound healing.

The goal of this research was to evaluate the beneficial effects of topical curcumin loaded freeze-dried wafers in wound healing. Curcumin wafers were fabricated by cross-linking of chitosan with beta glycerophosphate under magnetic stirring. Composite wafers were prepared by the addition of sodium hyaluronate. Wafers were fabricated by freeze-drying technique. The resulted wafers were examined by naked eye and their dimensions were measured using a caliper. % Drug content, in-vitro release and % water uptake tests were conducted to characterize the fabricated wafers. Porosity testing, compressive mechanical behavior, morphological examination using scanning electron microscopy, thermal behavior using differential scanning calorimetry and Fourier transform infrared spectroscopy were all carried out on the optimized cross-linked wafers followed by their microbiological assays and cytotoxicity studies. The results showed that the optimized wafers possessed high water uptake capabilities while entertaining very high porosity levels (86-89%). Microbiological assay revealed the superiority of the selected curcumin wafers versus free curcumin in bacterial growth inhibition against Staphylococcus epidermidis and Staphylococcus aureus (MRSA) bacteria. The anti-inflammatory effects of the selected curcumin wafers were evaluated against pro-inflammatory cytokines. The results suggested that they were significantly better than free curcumin in lowering cytokines levels. To conclude, the obtained findings revealed that curcumin wafers offered a promising solution in the field of wound healing.

Design and Characterization of Spray-Dried Proliposomes for the Pulmonary Delivery of Curcumin.

PURPOSE: The goal was to directly deliver curcumin, a natural polyphenolic anticancer and anti-inflammatory compound, to the lung tissues with minimal systemic exposure through the fabrication of proliposomes, overcoming its poor aqueous solubility and oral bioavailability. METHODS: Nano-spray drying was employed to prepare proliposomes using hydroxypropyl beta-cyclodextrin as a carrier. Lecithin and cholesterol were used as lipids, stearylamine and Poloxamer 188 were added as positive charge inducer and a surfactant, respectively. Different characterization parameters were evaluated like percentage yield, entrapment efficiency, drug loading, aerodynamic particle size, in vitro release besides morphological examination. Cytotoxicity studies on cell line A549 lung tumor cells as well as in vivo lung pharmacokinetic studies were also carried. RESULTS: The optimized formulations showed superior aerosolization properties coupled their enhanced ability to reach deep lung tissues with a high % of fine particle fraction. Cytotoxicity studies using MTT assay demonstrated enhanced growth inhibitory effect on lung tumor cells A549 and significant reduction of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6 and interleukin-10 compared to the pure drug. Results of lung pharmacokinetic tests confirmed the superiority of proliposomal curcumin over curcumin powder in both, the rate and extent of lung tissue absorption, as well as the mean residence time within the lung tissues. CONCLUSION: The pulmonary delivery of curcumin-loaded proliposomes as dry powder provides a direct approach to lung tissues targeting while avoiding the limitations of the oral route and offering a non-invasive alternative to the parenteral one.

In-situ forming chitosan implant-loaded with raloxifene hydrochloride and bioactive glass nanoparticles for treatment of bone injuries: Formulation and biological evaluation in animal model.

In-situ forming implants receive great attention for repairing serious bone injuries. The aim of the present study was to prepare novel chitosan in-situ forming implants (CIFI) loaded with bioactive glass nanoparticles and/or raloxifene hydrochloride (RLX). Incorporating raloxifene hydrochloride (RLX) as a selective estrogen receptor modulator was essential to make use of its anti-resorptive properties. The prepared formulae were tested for their in-vitro gelation time, drug release, injectability, rheological properties, erosion rate and morphological properties. Results revealed that the formulation composed of 1% (w/v) chitosan with 2% (w/v) NaHCO3 and 1% (w/v) bioactive glass nanoparticles (CIFI-BG) possessed the most sustained drug release profile which extended over four months with low burst release effect compared to the same formulation lacking bioactive glass nanoparticles (CIFI). Selected formulations were tested for their ability to enhance bone regeneration in induced puncture in rate tibia. Results declared that these formulations were able to enhance bone regeneration after 12 weeks in comparison to the untreated tibial punctures and that containing bioactive glass could be considered as novel approach for treatment of serious bone injuries which require long term treatment and internal mechanical bone support during healing.

Design and characterization of emulsified spray dried alginate microparticles as a carrier for the dually acting drug roflumilast.

Roflumilast is a selective inhibitor of phosphodiesterase-4 isoenzyme in lung cells. Having psychiatric adverse reactions when administered orally affects negatively the patients' adherence to the drug. This work aimed to prepare emulsified spray dried alginate microparticles for the pulmonary delivery of roflumilast. Sodium alginate was used as microparticle-forming material, isopropyl myristate as an oil, Tween®80 as surfactant and calcium beta-glycerophosphate as cross-linking agent to enhance the mechanical properties of the particles. The prepared particles were evaluated for their encapsulation efficiency, particle size and in-vitro drug release. From the studied carriers, beta-cyclodextrin (CD) was the best regarding giving formulation with smaller particle size and more sustained drug release. The inhalation profile of CD-based microparticles was investigated using Anderson cascade impactor. The aerosolization profile of CD-based microparticles suggested their efficiency to deliver the drug deep in the lung. The CD-based microparticles possessed more inhibitory effects on the viability of A549 cells and on the pro-inflammatory cytokines (TNF-α, IL-6 and IL-10) compared to the pure drug. Hence, CD-based microparticles could regulate the tumorigenesis besides tumor-associated inflammation. Finally, CD-based microparticles showed more sustained bronchodilatation properties in healthy human volunteers when compared to Ventolin®HFA. CD-based microparticles proved to be a promising carrier for inhaled roflumilast in human.