Phospholipid Free Nano-Vesicles of Brinzolamide Biopolymer Ocular Insert; Design, In vitro and In vivo Evaluation.

The aim of this work to study the feasibility of using phospholipid free vesicles with positive charge inducer in a slowly dissolving polymer ocular insert to successfully control intraocular pressure (IOP) for an extended period. Brinzolamide (BRNZ) was chosen as a model drug and a full factorial design was assembled to investigate the drug loading effect, ratio of cholesterol to fatty moiety and the type of the fatty moiety used on the vesicle size and entrapment efficiency. Linear regression models were constructed, and optimization of the formulation compositions yielded two formulae with palmitic acid as a negatively charged vesicles and cetrimide positively charged vesicles. Both formulae were studied in term of permeation efficiency through bovine corneal membranes. Positively charged vesicles although it didn't achieve the highest flux and cumulative amount permeated per unit surface area in the experiment time course, it achieved the highest retention of drug inside the corneal tissue, so it was chosen to be incorporated in a slowly dissolving polymer ocular insert. The insert was evaluated in term content, physical evaluation, and release properties. In vivo evaluation of the casted ocular inserts was conducted in male albino rabbits against market eye drop product and IOP readings were collected for 48 hours. The positively charged sterosomes containing BRNZ and formulated in polymer ocular inserts achieved extended control of IOP of the test animals compared to the market product.

Design of transfersomal nanocarriers of nystatin for combating vulvovaginal candidiasis; A different prospective.

The objective of this study was to prepare and evaluate Nystatin (NYS) loaded transfersomes to achieve better treatment of vulvovaginal candidiasis. Nystatin transferosomes were formulated utilizing thin film hydration method. A 32 full factorial design was employed to evaluate the effect of different formulation variables. Two independent variables were chosen; the ratio between lecithin surfactant (X1) was set at three levels (10-40), and the type of surfactants (X2) was set at three levels (Span 60, Span 85 and Pluronic F-127). The dependent responses were; entrapment efficiency (Y1: EE %), vesicles size (Y2: VS) and release rate (Y3: RR). Design Expert® software was utilized to statistically optimize formulation variables. The vesicles revealed high NYS encapsulation efficiency ranging from 97.35 ± 0.03 to 98.01 ± 0.20% whereas vesicle size ranged from 194.8 ± 20.42 to 400.8 ± 42.09 nm. High negative zeta potential values indicated good stability of the prepared formulations. NYS release from transfersomes was biphasic and the release pattern followed Higuchi's model. The optimized formulation (F7) exhibited spherical morphology under transmission electron microscopy (TEM). In-vitro and in-vivo antifungal efficiency studies revealed that the optimized formula F7 exhibited significant eradication of candida infestation in comparison to free NYS. The results revealed that the developed NYS transfersomes could be a promising drug delivery system to enhance antifungal efficacy of NYS.

Nanofibrous ε-polycaprolactone scaffolds containing Ag-doped magnetite nanoparticles: Physicochemical characterization and biological testing for wound dressing applications in vitro and in vivo.

Skin wounds can lead to numerous complications with dangerous health consequences. In this work, magnetite nanoparticles were doped with different concentrations of antimicrobial silver (Ag) ions and incorporated into the electrospun nanofibrous ε-polycaprolactone (PCL) scaffolds. Nanoparticles and scaffolds with various Ag contents were characterized using a range of physicochemical techniques. Ag entered magnetite as cations and preferentially positioned at tetrahedral sites, introducing lattice distortions and topographic irregularities. Amorphization of the structure due to accommodation of Ag expanded the lattice in the bulk and contracted it on the surface, where broadened distribution of Fe-O coordinations was detected. Promoting spin canting and diminishing the double exchange interaction through altered distribution of ferric and ferrous ions, Ag softened the magnetism of magnetite. By making the nanoparticle structure more defective, Ag modified the interface with the polymer and promoted the protrusion of the nanoparticles from the surface of the polymeric nanofibers, thus increasing their roughness and hydrophilicity, with positive repercussions on cell adhesion and growth. Both the viability of human melanocytes and the antibacterial activity against E. coli and S. aureus increased with the concentration of Ag in the magnetite phase of the scaffolds. Skin wound healing rate in rats also increased in direct proportion with the concentration of Ag in the magnetite phase, and no abnormalities in the dermal and epidermal tissues were visible on day 10 in the treatment group. These results imply an excellent potential of these composite nanofibrous scaffolds for use as wound dressings and in other reconstructive skin therapies.

Polycaprolactone based electrospun matrices loaded with Ag/hydroxyapatite as wound dressings: Morphology, cell adhesion, and antibacterial activity.

The development of a scaffold matrix that can inhibit bacterial infection and promote wound healing simultaneously is an essential demand to improve the health care system. Hydroxyapatite (HAP) doped with different concentrations of silver ions (Ag+) were incorporated into electrospun nanofibrous scaffolds of polycaprolactone (PCL) using the electrospinning technique. The formed phase was identified using XRD, while the morphological and roughness behavior were investigated using FESEM. It was shown that scaffolds were configured in randomly distributed nanofibers with diameters around of 0.19-0.40, 0.31-0.54, 1.36, 0.122-0.429 µm for 0.0Ag-HAP@PCL, 0.2Ag-HAP@PCL, 0.6Ag-HAP@PCL, and 0.8Ag-HAP@PCL, respectively. Moreover, the maximum roughness peak height increased significantly from 179 to 284 nm, with the lowest and highest contributions of Ag. The mechanical properties were examined and displayed that the tensile strength increased from 3.11 ± 0.21 MPa to its highest value at 3.57 ± 0.31 MPa for 0.4Ag-HAP@PCL. On the other hand, the cell viability also was enhanced with the addition of Ag and improved from 97.1 ± 4.6% to be around 102.3 ± 3.1% at the highest contribution of Ag. The antibacterial activity was determined, and the highest imbibition zones were achieved at the highest Ag dopant to be 12.5 ± 1.1 mm and 11.4 ± 1.5 mm against E. coli and S. aureus. The in vitro cell proliferation was observed through human fibroblasts cell lone (HFB4) and illustrated that cells were able to grow and spread not only on the fibers' surface but also, they were spreading and adhered through the deep pores.