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In this work, Tamarindus indica (T. indica)-loaded crosslinked poly(methyl methacrylate) (PMMA)/cellulose acetate (CA)/poly(ethylene oxide) (PEO) electrospun nanofibers were designed and fabricated for wound healing applications. T. indica is a plant extract that possesses antidiabetic, antimicrobial, antioxidant, antimalarial and wound healing properties. T. indica leaves extract of different concentrations were blended with a tuned composition of a matrix comprised of PMMA (10 %), CA (2 %) and PEO (1.5 %), and were electrospun to form smooth, dense and continuous nanofibers as illustrated by SEM investigation. In vitro evaluation of T. indica-loaded nanofibers on normal human skin fibroblasts (HBF4) revealed a high compatibility and low cytotoxicity. T. indica-loaded nanofibers significantly increased the healing activity of scratched HBF4 cells, as compared to the free plant extract, and the healing activity was significantly enhanced upon increasing the plant extract concentration. Moreover, T. indica-loaded nanofibers demonstrated significant antimicrobial activity in vitro against the tested microbes. In vivo, nanofibers resulted in a superior wound healing efficiency compared to the control untreated animals. Hence, engineered nanofibers loaded with potent phytochemicals could be exploited as an effective biocompatible and eco-friendly antimicrobial biomaterials and wound healing composites., Competing Interests: Declaration of competing interest The authors declare no competing of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Exploitation of nanocarriers provides a compartment for enclosing drugs to protect them from degradation and potentiate their therapeutic efficiency. In the current study, amitriptyline- and liraglutide-loaded proniosomes were constructed for management of diabetic neuropathy, a serious complication associated with diabetes, that triggers spontaneous pain in patients and results in impaired quality of life. The developed therapeutic proniosomes were extensively characterized via dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and Fourier transform-infrared spectroscopy. High entrapment efficiency could be attained for both drugs in the proniosomes, and the reconstituted amitriptyline- and liraglutide-loaded niosomes possessed spherical morphology and particle sizes of 585.3 nm and 864.4 nm, respectively. In a diabetic neuropathy rat model, oral administration of the developed amitriptyline- and liraglutide-loaded proniosomes significantly controlled blood glucose levels, reduced neuropathic pain, oxidative stress and inflammatory markers, and improved histological structure of the sciatic nerve as compared to the oral and subcutaneous administration of amitriptyline and liraglutide, respectively. Loading of the tricyclic antidepressant amitriptyline and the antidiabetic peptide liraglutide into proniosomes resulted in exceptional control over hyperglycemia and neuropathic pain, and thus could provide an auspicious delivery system for management of neuropathic pain and control of blood glucose levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Morphologic design of nanomaterials for a diversity of biomedical applications is of increasing interest. The aim of the current study is to construct therapeutic gold nanoparticles of different morphologies and investigate their effect on ocular retention and intraocular pressure in a glaucoma rabbit model. Poly(lactic-co-glycolic acid) (PLGA)-coated nanorods and nanospheres have been synthesized and loaded with carbonic anhydrase inhibitor (CAI), and characterized in vitro for their size, zeta potential and encapsulation efficiency. Nanosized PLGA-coated gold nanoparticles of both morphologies demonstrated high entrapment efficiency (˃ 98%) for the synthesized CAI and the encapsulation of the drug into the developed nanoparticles was confirmed via Fourier transform-infrared spectroscopy. In vivo studies revealed a significant reduction in intraocular pressure upon instillation of drug-loaded nanogold formulations compared to the marketed eye drops. Spherical nanogolds exhibited a superior efficacy compared to the rod-shaped counterparts, probably due to the enhanced ocular retention of spherical nanogolds within collagen fibers of the stroma, as illustrated by transmission electron microscopy imaging. Normal histological appearance was observed for the cornea and retina of the eyes treated with spherical drug-loaded nanogolds. Hence, incorporation of a molecularly-designed CAI into nanogold of tailored morphology may provide a promising strategy for management of glaucoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Overexpression of two carbonic anhydrase (CA) isoforms, CA IX and XII, in several hypoxic solid tumors provides an extracellular hypoxic microenvironment, interferes with extra- and intracellular pH regulation, thus favoring hypoxic tumor cell survival, proliferation and metastasis. In the current study, a selective inhibitor for human CA isoforms IX and XII (isatin-bearing sulfonamide, WEG-104), was incorporated into nanosized spherical niosomes at high encapsulation efficiency to allow for an enhanced and sustained antitumor activity. In vivo, administration of WEG-104 that is either free (10 mg/kg) or loaded into niosomes (5 mg/kg) into a mice model of Ehrlich ascites solid tumor resulted in comparable efficacy in terms of reduction of tumor weight and volume. Administration of WEG-104-loaded niosomes (10 mg/kg) exhibited superior antitumor activity compared to the free drug, evidenced by reduced tumor weight and volume, marked reduction in the activity of CA IX and XII, and suppression of HIF-1α and MMP-2. Moreover, prominent increase of caspase 3 and pronounced decrease in VEGF immune expression were observed in the treated animals. Hence, loading of molecularly designed compounds that targets CAs in hypoxic solid tumors into nanosized delivery systems provided an auspicious strategy for limiting solid tumor progression and malignancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Intravenous dexmedetomidine (DEX) is currently approved by the FDA for the sedation of intubated patients in intensive care units to reduce anxiety and to augment postoperative analgesia. Bradycardia and hypotension are limitations associated with the intravenous administration of DEX. In this study, DEX sublingual in situ gels were developed and assessed for their pH, gelling capacity, viscosity, mucoadhesion and in vitro drug release. The optimized gelling system demonstrated enhanced mucoadhesion, superior gelling capacity, reasonable pH and optimal rheological profile. In vivo, compared to the oral solution, the optimal sublingual gel resulted in a significant higher rate and extent of bioavailability. Although the in situ gel had comparable plasma levels to those observed following intravenous administration, significant amelioration of the systemic adverse reactions were attained. As demonstrated by the hot plate method, a sustained duration of analgesia in rats was observed after sublingual administration of DEX gel compared to the intravenously administered DEX solution. Furthermore, no changes in systolic blood pressure and heart rate were recorded in rats and rabbits, respectively, after sublingual administration of DEX. Sublingual administration of DEX in situ gel provides a promising approach for analgesia and sedation, while circumventing the reported adverse reactions associated with intravenous administration of DEX.