Novel long-acting brimonidine tartrate loaded-PCL/PVP nanofibers for versatile biomedical applications: fabrication, characterization and antimicrobial evaluation.

The global state of antibiotic resistance highlights the necessity for new drugs that can treat a wide range of microbial infections. Drug repurposing has several advantages, including lower costs and improved safety compared to developing a new compound. The aim of the current study is to evaluate the repurposed antimicrobial activity of Brimonidine tartrate (BT), a well-known antiglaucoma drug, and to potentiate its antimicrobial effect by using electrospun nanofibrous scaffolds. BT-loaded nanofibers were fabricated in different drug concentrations (1.5, 3, 6, and 9%) via the electrospinning technique using two biopolymers (PCL and PVP). Then, the prepared nanofibers were characterized by SEM, XRD, FTIR, swelling ratio, and in vitro drug release. Afterward, the antimicrobial activities of the prepared nanofibers were investigated in vitro using different methods against several human pathogens and compared to the free BT. The results showed that all nanofibers were prepared successfully with a smooth surface. The diameters of nanofibers were reduced after loading of BT compared to the unloaded ones. In addition, scaffolds showed controlled-drug release profiles that were maintained for more than 7 days. The in vitro antimicrobial assessments revealed good activities for all scaffolds against most of the investigated human pathogens, particularly the one prepared with 9% BT which showed superiority in the antimicrobial effect over other scaffolds. To conclude, our findings proved the capability of nanofibers in loading BT and improving its repurposed antimicrobial efficacy. Therefore, it could be a promising carrier for BT to be used in combating numerous human pathogens.

Smart biomaterials for enhancing cancer therapy by overcoming tumor hypoxia: a review.

Hypoxia is a distinctive feature of most solid tumors due to insufficient oxygen supply of the abnormal vasculature, which cannot work with the demands of the fast proliferation of cancer cells. One of the main obstacles to limiting the efficacy of cancer medicines is tumor hypoxia. Thus, oxygen is a vital parameter for controlling the efficacy of different types of cancer therapy, such as chemotherapy (CT), photodynamic therapy (PDT), photothermal therapy (PTT), immunotherapy (IT), and radiotherapy (RT). Numerous technologies have attracted much attention for enhancing oxygen distribution in humans and improving the efficacy of cancer treatment. Such technologies include treatment with hyperbaric oxygen therapy (HBO), delivering oxygen by polysaccharides (e.g., cellulose, gelatin, alginate, and silk) and other biocompatible synthetic polymers (e.g., PMMA, PLA, PVA, PVP and PCL), decreasing oxygen consumption, producing oxygen in situ in tumors, and using polymeric systems as oxygen carriers. Herein, this review provides an overview of the relationship between hypoxia in tumor cells and its role in the limitation of different cancer therapies alongside the numerous strategies for oxygen delivery using polysaccharides and other biomaterials as carriers and for oxygen generation.

Mercaptopurine-Loaded Sandwiched Tri-Layered Composed of Electrospun Polycaprolactone/Poly(Methyl Methacrylate) Nanofibrous Scaffolds as Anticancer Carrier with Antimicrobial and Antibiotic Features: Sandwich Configuration Nanofibers, Release Study and in vitro Bioevaluation Tests.

BACKGROUND: 6-Mercaptopurine (6-MP) is a potential anti-cancer agent which its therapeutic and limitation applicability due to its high toxicity. OBJECTIVE: Herein, 6-MP was loaded into tri-layered sandwich nanofibrous scaffold (the top layer composed of poly methyl methacrylate/polycaprolactone (PMMA/PCL), the middle layer was PCL/PMMA/6-MP, and the bottom layer was PCL/PMMA to improve its bioactivity, adjusting the release-sustainability and reduce its toxicity. METHODS: Electrospun tri-layered nanofibers composed of PCL/PMMA were utilized as nano-mats for controlling sustained drug release. Four groups of sandwich scaffold configurations were investigated with alteration of (PMMA: PCL) composition. RESULTS: The sandwich scaffold composed of 2%PCL/4%PMMA/1%6-MP showed the best miscibility, good homogeneity and produced the smoothest nanofibers and low crystallinity. All fabricated 6-MP-loaded-PCL/PMMA scaffolds exhibited antimicrobial properties on the bacterial and fungal organisms, where the cytotoxicity evaluation proved the safety of scaffolds on normal cells, even at high concentration. Scaffolds provided a sustained-drug release profile that was strongly dependent on (PCL: PMMA). As (PCL: PMMA) decreased, the sustained 6-MP release from PCL/PMMA scaffolds increased. Results established that ~18% and 20% of 6-MP were released after 23h from (4%PCL/4%PMMA/1%6-MP) and (2%PCL/4%PMMA/1%6-MP), respectively, where this release was maintained for more than 20 days. The anti-cancer activity of all fabricated scaffolds was also investigated using different cancerous cell lines (e.g., Caco-2, MDA, and HepG-2) results showed that 6-MP-loaded-nanofibrous mats have an anti-cancer effect, with a high selective index for breast cancer. We observed that viability of a cancer cell was dropped to about 10%, using nanofibers containing 2%PCL/4%PMMA/1%6-MP. CONCLUSION: Overall, the PCL: PMMA ratio and sandwich configuration imparts a tight control on long-term release profile and initial burst of 6-MP for anticancer treatment purposes.

Green Nanotechnology in the Formulation of a Novel Solid Dispersed Multilayered Core-Sheath Raloxifene-Loaded Nanofibrous Buccal Film; In Vitro and In Vivo Characterization.

Green nanotechnology utilizes the principles of green chemistry to formulate eco-friendly nanocarrier systems to mitigate patients and environment hazards. Raloxifene (RLX) demonstrates poor aqueous solubility (BCS class II) and low bioavailability, only 2% (extensive first-pass metabolism). The aim of this study is to enhance RLX solubility and bioavailability via development of novel solid dispersed multilayered core-sheath RLX-loaded nanofibers (RLX-NFs) without the involvement of organic solvents. A modified emulsion electrospinning technique was developed. Electrospinning of an RLX-nanoemulsion (RLX-NE) with polymer solution (poly vinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC), and chitosan (CS) in different volume ratios (1:9, 2:8, and 4:6) using D-optimal response surface methodology was adopted. In vitro characterization of RLX-loaded NFs was performed; scanning electron microscope (SEM), thermal analysis, drug content, release studies, and bioadhesion potential. The optimum NFs formula was evaluated for morphology using high-resolution transmission electron microscopy (HRTEM), and ex vivo drug permeation. The superiority of E2 (comprising RLX-NE and PVA (2:8)) over other NF formulae was statistically observed with respect to Q60 (56.048%), Q240 (94.612%), fiber size (594.678 nm), mucoadhesion time 24 h, flux (5.51 µg/cm2/h), and enhancement ratio (2.12). RLX pharmacokinetics parameters were evaluated in rabbits following buccal application of NF formula E2, relative to RLX oral dispersion. E2 showed significantly higher Cmax (53.18 ± 4.56 ng/mL), and relative bioavailability (≈2.29-fold).

Novel oxygen-generation from electrospun nanofibrous scaffolds with anticancer properties: synthesis of PMMA-conjugate PVP-H2O2 nanofibers, characterization, and in vitro bio-evaluation tests.

Released oxygen plays a critical role in reducing destructive tumor behavior. This study aims to utilize decomposed hydrogen peroxide as an oxygen source by conjugating it with polyvinylpyrrolidone (PVP). PVP-hydrogen peroxide complex (PHP) composed of different ratios of (PVP : H2O2) (0.5 : 1, 1 : 1, 1 : 1.5, 1 : 5, and 1 : 10) were successfully synthesized. PHP complex with a ratio of 1 : 1.5 was chosen as the optimized ratio, and it was incorporated into the polymethyl methacrylate (PMMA) nanofibrous scaffold via the electrospinning technique. Results have revealed that the PMMA-10% PHP complex provided a significant morphological structure of nanofibrous scaffolds. The mechanical properties of PMMA-10% PHP nanofibers showed the most suitable mechanical features such as Young's modulus, elongation-at-break (%), and maximum strength, in addition to the highest degree of swelling. All PHP complex scaffolds released oxygen in a sustained manner. However, the PMMA-10% PHP complex gave the highest concentration of released-oxygen with (∼8.9 mg L-1, after 2.5 h). PMMA-10% PHP nanofibers provided an ideal model for released-oxygen scaffold with anti-cancer effect and high selectivity for cancer cells, especially for breast cancer cells. Nanofibrous scaffolds with different composition revealed high cell viability for normal cells. Such outcomes support the suitability of using synthesized nanofibrous scaffolds as released-oxygen biomaterials to enhance cancer cells' sensitivity and maximize the treatment effect.

Electrospun PVA/hyaluronic acid/L-arginine nanofibers for wound healing applications: Nanofibers optimization and in vitro bioevaluation.

Hyaluronic acid (HA) based nanofibers (NFs) represented a novel class of bioactive wound dressings that have a vital role in wound management due to their unique properties as an extracellular-matrix and accelerating wound healing. Novel L-arginine-loaded citric acid crosslinked PVA-HA NFs were fabricated by electrospinning and proposed for potential wound healing purposes. However, poor mechanical properties of HA NFs might limit its biological usage, thus this study aims to develop reinforced PVA/HA NFs by incorporation of cellulose nanocrystals (CNCs) as nanofiller and loading L-arginine as wound healing accelerator. Results revealed that incorporation of CNCs into PVA/HA significantly improved mechanical and swelling properties of NFs, compared to CNC-free NFs. Biological performance of NFs was evaluated on normal human skin melanocyte (HFB-4) and lung fibroblast (WI38) cell-lines. PVA/HA/CNC/L-arginine NFs exhibited excellent hemocompatibility, high protein adsorption, outstanding proliferative and adhesive potential on HFB-4 cells expressed by high wound gap-closure 99.9% after 48 h of exposure. Released arginine from PVA/HA/CNC NFs showed sustained release about 46.5% and ~90% after 24 h and 48 h, respectively. Briefly, PVA/HA/CNCs/L-arginine showed adequate antibacterial activity especially against Klebsiella pneumonia, as an acute popular pathogen causing a skin infection. These results indicate that PVA/HA/CNC/L-arginine could act as promising and multifunctional wound dressings.