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Burns are potentially fatal and physically debilitating injuries, causing psychological and physical scars and result in chronic disabilities. A well vascularized wound bed is required to achieve complete and scar free wound closure. For many centuries, a variety of herbal plants have been used for wound healing, among these aloe vera (AV) has been found to be very effective in wound healing. Secondly, the main reason for delayed wound healing is bacterial infections. Ofloxacin (OX) has been reported as an active antibacterial drug for topical infections and it is effective against both positive and negative bacterial strains. In current research three different concentrations of OX (0.5, 2.5, and 5 mg) were loaded into chitosan (CS)/AV based hydrogels prepared by freeze gelation. The surface morphology of prepared CS/AV based OX loaded hydrogels were evaluated by scanning electron microscopy (SEM). In drug release analysis, 0.5 mg OX loaded hydrogel showed a sustained drug release behavior over 3 days period. An effective dose dependent antibacterial activity was exhibited by OX loaded hydrogels. Alamar Blue cells viability assay revealed that 0.5 mg OX hydrogel (CA 0.5 OX) showed comparatively better 3 T3 fibroblast cells proliferation as compared to CA 2.5 OX (2.5 mg OX) and CA 5 OX hydrogel (5 mg OX). Moreover, all OX loaded hydrogels showed good angiogenic activity in CAM bioassay while higher angiogenic potential was observed from CA 0.5 OX containing comparatively lower concentration of OX. These OX incorporated CS/AV based hydrogels are promising wound dressings for future clinical use.

Use of medicinal plants for the biosynthesis of nanoparticles offers several advantages over other synthesis approaches.

Hydrogels have been the material of choice for regenerative medicine applications due to their biocompatibility that can facilitate cellular attachment and proliferation. The present study aimed at constructing a porous hydrogel composite scaffold (chitosan, sodium alginate and elastin) for the repair of chronic skin wounds. Chitosan-based hydrogel incorporating varying concentrations of zinc oxide nanoparticles i.e. ZnO-NPs (0, 0.001, 0.01, 0.1 and 1 % w/w) as the antimicrobial agent tested against Escherichia coli (E.coli) and Staphylococcus aureus (S. aureus) exhibited good antibacterial activities. ZnO-NPs were characterized by UV visible spectroscopy, Scanning electron microscopy (SEM) analysis, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis. Fabricated gels were characterized by SEM analysis, FTIR, XRD, swelling ratio, degradation behavior and controlled release kinetics of ZnO-NPs. In vitro cytocompatibility of the composite was investigated using human adipose stem cells (ADSCs) by MTT and lactate dehydrogenase (LDH) assay, further assessed by SEM analysis and PKH26 staining. The SEM and XRD analysis confirmed the successful loading of ZnO-NPs into these scaffolds. Fluorescence PKH26 stained images and SEM analysis of ADSCs seeded scaffolds revealed biocompatible nature. The findings suggested that the developed composite gels have potential clinically for tissue engineering and chronic wound treatment. The authors acknowledge Dr. Muhammad Ali, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA, for checking the manuscript for English language, grammar, style and syntax. The authors acknowledge Higher Education Commission Pakistan for providing funding for conduct of this work from TDF 02-163 (Dr. Azra Mehmood) and HEC NRPU Project number 8762 (Dr. Muhammad Yar). Scopus

Delay in wound healing is a diabetes mellites resulting disorder causing persistent microbial infections, pain, and poor quality of life. This disorder is treated by several strategies using natural biomaterials, growth factors and stem cells molded into various scaffolds which possess the potential to accelerate the closure of impaired diabetic wounds. In this study, we developed a hydrogel patch using chitosan (CS) and polyethylene glycol (PEG) with laden bone marrow-derived mesenchymal stem cells (BMSCs) that were pretreated with fibroblast growth factor 21 (FGF21). The developed hydrogel patches were characterized by scanning electron microscopy and fourier transform infrared (FTIR) spectroscopy. After studying the swelling behavior, growth factor (FGF21) was used to modulate BMSC in the hyperglycemic environment. Later, FGF21 treated BMSC were embedded in CS/PEG hydrogel patch and their wound closure effect was assessed in diabetic rats. The results showed that CS/PEG hydrogel patches have good biocompatibility and possess efficient BMSC recruiting properties. The application of CS/PEG hydrogel patches accelerated wound closure in diabetic rats as compared to the control groups. However, the use of FGF21 pretreated BMSCs laded CS/PEG hydrogel patches further increased the therapeutic efficacy of wound closure in diabetic rats. This study demonstrated that the application of a hydrogel patch of CS/PEG with FGF21 pretreated BMSCs improves diabetic wound healing, but further studies are needed on larger animals before the use of these dressings in clinical trials.

Platinum nanoparticles (PtNPs) are an attractive candidate for application in many areas of biotechnology, nanomedicine, and pharmacology, owing to their large surface area and biological properties. Different approaches, including physical, chemical, and biological (plants, bacteria, algae, and fungi) are presently being used for synthesis of PtNPs. However, these conventional methods (physical and chemical) present potential threat to health and environment because of the use of harsh chemicals and hazardous reaction conditions, except biological synthesis means which are substantially considered ecofriendly, economic and non-toxic. PtNPs are extensively studied due to their potent physicochemical and biological properties including antioxidant, antimicrobial and anticancer properties. This review offers a comprehensive assessment of the current knowledge about the synthesis of PtNPs using physical, chemical, and biological (plants, bacteria, algae, and fungi) approaches and their potential antimicrobial and biomedical applications especially in cancer and photothermal therapy. Interestingly, this review highlights role of PtNPs as nano-diagnostic and nanomedicine. Furthermore, nanotoxicity related to PtNPs, as well as the future prospects and opportunities of PtNPs based nano-therapeutics are also discussed. Overall, the emerging potential biological applications of PtNPs makes it viable to foresee their more promising outcomes in biomedical field in the upcoming future.

Simple Summary Cancer is one of the major public health burdens in the world. To date, various conventional cancer therapies have been used, but these therapies are less effective and have severe side effects. Currently, in order to find a better cure for cancer, researchers have tried to explore new approaches with minimal toxicity and fewer side effects. In recent years, nanotechnology has been widely used in diseases management and holds a promising future in curing complex incurable diseases, in particular cancer. Biosynthesized metallic nanoparticles are eco-friendly and biocompatible, and can be used in cancer diagnostics, novel treatments, and drug delivery systems. This review gives an overview of the recent advancements in the biosynthesis of metallic nanoparticles (silver (Ag), gold (Au), zinc (Zn) and copper (Cu)) and their possible anti-cancer activities, with particular emphasis on the mechanisms of action, and future research prospects of nano-therapeutics are also discussed. Abstract Cancer is one of the foremost causes of death worldwide. Cancer develops because of mutation in genes that regulate normal cell cycle and cell division, thereby resulting in uncontrolled division and proliferation of cells. Various drugs have been used to treat cancer thus far; however, conventional chemotherapeutic drugs have lower bioavailability, rapid renal clearance, unequal delivery, and severe side effects. In the recent years, nanotechnology has flourished rapidly and has a multitude of applications in the biomedical field. Bio-mediated nanoparticles (NPs) are cost effective, safe, and biocompatible and have got substantial attention from researchers around the globe. Due to their safe profile and fewer side effects, these nanoscale materials offer a promising cure for cancer. Currently, various metallic NPs have been designed to cure or diagnose cancer; among these, silver (Ag), gold (Au), zinc (Zn) and copper (Cu) are the leading anti-cancer NPs. The anticancer potential of these NPs is attributed to the production of reactive oxygen species (ROS) in cellular compartments that eventually leads to activation of autophagic, apoptotic and necrotic death pathways. In this review, we summarized the recent advancements in the biosynthesis of Ag, Au, Zn and Cu NPs with emphasis on their mechanism of action. Moreover, nanotoxicity, as well as the future prospects and opportunities of nano-therapeutics, are also highlighted.

Non-healing wounds are among the serious complications of type-2-diabetes around the globe, associated with high incidence of bacterial infection, chronic nerve and blood vessel damage, and eventually repeated amputation of limbs and organs. Silver nanoparticles offer strong wound healing potential due to their well-known antibacterial activities. The present study reports the development of silver nanoparticle impregnated chitosan-poly ethylene glycol (PEG) hydrogel to accelerate wound healing in diabetic patients. The aim of the study was to formulate a sustained and slow release of silver nanoparticle using chitosan-PEG-Silver Nitrate based hydrogel for the treatment of chronic diabetic wounds. The silver nanoparticle containing chitosan-PEG pre-polymer solution was synthesized by reducing silver nitrate with PEG and chitosan solution, thereby, transforming the silver ions into silver nanoparticles. The resulted pre-polymer solution was then crosslinked using glutaraldehyde to form the desired hydrogel. The developed silver nanoparticle impregnated chitosan hydrogel was characterized using ultra-violet (UV) visible spectrophotometry, Fourier Transform-infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) followed by the determination of porosity, and swelling properties. The release of AgNPs from hydrogel was determined by UV-vis spectroscopy followed by antimicrobial and antioxidant assays. The wound healing efficacy of the synthesized hydrogel was evaluated in diabetic rabbits. The results demonstrated a higher porosity, higher degree of swelling and higher water vapor transition rate (WVTR) for silver nanoparticle impregnated hydrogel compared to bare chitosan-PEG hydrogel as well as improved antimicrobial and antioxidant properties in-vitro and enhanced wound healing capability in-vivo in diabetic rabbits. The hydrogel showed a slow and sustained release of AgNPs over a period of at least seven days manifesting the slow biodegradation of developed hydrogels. The improved antimicrobial, antioxidant and wound healing results indicate that the silver nanoparticle impregnated chitosan-PEG hydrogel can be a promising material for wound healing dressing for chronic diabetic wounds. This article was made possible by the NPRP9-144-3-021 grant funded by Qatar national Research Fund (a part of Qatar Foundation ). The statements made here are totally responsibility of authors. The authors also thankfully acknowledge Mirpur University of Science and Technology ( MUST ), Mirpur, AJK, Pakistan for providing their facilities needed for completion of current study. Scopus

The anti-cancer, anti-aging, anti-inflammatory, antioxidant, and anti-diabetic effects of zinc oxide nanoparticles (ZnO-NPs) produced from aqueous leaf extract of Aquilegia pubiflora were evaluated in this study. Several methods were used to characterize ZnO-NPs, including SEM, FTIR, XRD, DLS, PL, Raman, and HPLC. The nanoparticles that had a size of 34.23 nm as well as a strong aqueous dispersion potential were highly pure, spherical or elliptical in form, and had a mean size of 34.23 nm. According to FTIR and HPLC studies, the flavonoids and hydroxycinnamic acid derivatives were successfully capped. Synthesized ZnO-NPs in water have a zeta potential of -18.4 mV, showing that they are stable solutions. The ZnO-NPs proved to be highly toxic for the HepG2 cell line and showed a reduced cell viability of 23.68 ± 2.1% after 24 hours of ZnO-NP treatment. ZnO-NPs also showed excellent inhibitory potential against the enzymes acetylcholinesterase (IC50: 102 μg/mL) and butyrylcholinesterase (IC50: 125 μg/mL) which are involved in Alzheimer's disease. Overall, the enzymes involved in aging, diabetes, and inflammation showed a moderate inhibitory response to ZnO-NPs. Given these findings, these biosynthesized ZnO-NPs could be a good option for the cure of deadly diseases such as cancer, diabetes, Alzheimer's, and other inflammatory diseases due to their strong anticancer potential and efficient antioxidant properties.

The central nervous system (CNS) encompasses the brain and spinal cord and is considered the processing center and the most vital part of human body. The central nervous system (CNS) barriers are crucial interfaces between the CNS and the periphery. Among all these biological barriers, the blood-brain barrier (BBB) strongly impede hurdle for drug transport to brain. It is a semi-permeable diffusion barrier against the noxious chemicals and harmful substances present in the blood stream and regulates the nutrients delivery to the brain for its proper functioning. Neurological diseases owing to the existence of the BBB and the blood-spinal cord barrier have been terrible and threatening challenges all over the world and can rarely be directly mediated. In fact, drug delivery to brain remained a challenge in the treatment of neurodegenerative (ND) disorders, for these different approaches have been proposed. Nano-fabricated smart drug delivery systems and implantable drug loaded biomaterials for brain repair are among some of these latest approaches. In current review, modern approaches developed to deal with the challenges associated with transporting drugs to the CNS are included. Recent studies on neural drug discovery and injectable hydrogels provide a potential new treatment option for neurological disorders. Moreover, induced pluripotent stem cells used to model ND diseases are discussed to evaluate drug efficacy. These protocols and recent developments will enable discovery of more effective drug delivery systems for brain.

The anti-cancer, anti-aging, anti-inflammatory, antioxidant, and anti-diabetic effects of zinc oxide nanoparticles (ZnO-NPs) produced from aqueous leaf extract of Aquilegia pubiflora were evaluated in this study. Several methods were used to characterize ZnO-NPs, including SEM, FTIR, XRD, DLS, PL, Raman, and HPLC. The nanoparticles that had a size of 34.23 nm as well as a strong aqueous dispersion potential were highly pure, spherical or elliptical in form, and had a mean size of 34.23 nm. According to FTIR and HPLC studies, the flavonoids and hydroxycinnamic acid derivatives were successfully capped. Synthesized ZnO-NPs in water have a zeta potential of -18.4 mV, showing that they are stable solutions. The ZnO-NPs proved to be highly toxic for the HepG2 cell line and showed a reduced cell viability of 23.68 ± 2.1 % after 24 hours of ZnO-NP treatment. ZnO-NPs also showed excellent inhibitory potential against the enzymes acetylcholinesterase (IC50: 102 μg/mL) and butyrylcholinesterase (IC50: 125 μg/mL) which are involved in Alzheimer’s disease. Overall, the enzymes involved in aging, diabetes, and inflammation showed a moderate inhibitory response to ZnO-NPs. Given these findings, these biosynthesized ZnO-NPs could be a good option for the cure of deadly diseases such as cancer, diabetes, Alzheimer’s, and other inflammatory diseases due to their strong anticancer potential and efficient antioxidant properties.

The absorption capacity of cotton dressings is a critical factor in their widespread use where they help absorb wound exudate. Cotton wax dressings, in contrast, are used for wounds where care is taken to avoid adhesion of dressings to sensitive wounds such as burn injuries. Accordingly, we explored the loading of 2‐deoxy‐D‐ribose (2dDR), a small sugar, which stimulates angiogenesis and wound healing in normal and diabetic rats, into both types of dressings and measured the release of it over several days. The results showed that approximately 90% of 2dDR was released between 3 and 5 days when loaded into cotton dressings. For wax‐coated cotton dressings, several methods of loading of 2dDR were explored. A strategy similar to the commercial wax coating methodology was found the best protocol which provided a sustained release over 5 days.\ud \ud Cytotoxicity analysis of 2dDR loaded cotton dressing showed that the dressing stimulated metabolic activity of fibroblasts over 7 days confirming the non‐toxic nature of this sugar‐loaded dressings. The results of the chick chorioallantoic membrane (CAM) assay demonstrated a strong angiogenic response to both 2dDR loaded cotton dressing and to 2dDR loaded cotton wax dressings. Both dressings were found to increase the number of newly formed blood vessels significantly when observed macroscopically and histologically.\ud \ud We conclude this study offers a simple approach to developing affordable wound dressings as both have the potential to be evaluated as pro‐active dressings to stimulate wound healing in wounds where management of exudate or prevention of adherence to the wounds are clinical requirements.

Alzheimer’s disease (AD) is the most prevalent form of dementia. Improving the amount of acetylcholine in the brain is an efficient way to treat the illness. The global incidence of dementia is estimated to be as high as 50 million, and it is expected to increase every 20 years until 2040, resulting in a costly burden of disease. Early-life risk factors for pathology include genes, chromosomal abnormalities, head injury, insulin resistance, and inflammation. Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer’s disease (AD) and represent promising targets for intervention. The drugs currently being used to manage AD have various drawbacks. The chemical inhibition of cholinesterase enzymes is an effective technique for treating signal related neuropathology, and possible sources of compounds with these properties are natural products and biogenic metal oxide nanoparticles. There is a potential source of AChE and BChE inhibitors in the abundance of plants in nature, and natural goods appear to offer useful medications and templates for the development of other compounds. This dissertation represents a review of the literature on species of medicinal plants and nanomaterial related plants tested for their inhibitory action of AChE and BChE. Plant species and the plant-mediated metal oxide nanoparticles referred to are possible cholinesterase inhibitors and can assist researchers in their study of natural products that may be beneficial in the treatment of AD.

Syzygium cumini (S. cumini) is an evergreen tropical plant that is well recognized for its therapeutic potential of common diseases. In this study, the therapeutic potential and biomedical application of S. cumini are assessed in vitro and in vivo to find its effectiveness for different complications. The methanolic crude extract of S. cumini leaves were screened for total phenolic and flavonoid content. In vitro, the DPPH scavenging assay, XTT assay, prothrombin and activated partial thromboplastin time were used to assess antioxidant, cytoprotective and thrombolytic activity of the S. cumini extract, respectively. The anti-inflammatory potential and the analgesic activity of the S. cumini extract were analyzed in rabbits by the Carrageenan induced paw edema method and the writhing method, respectively. Phytochemical analysis showed the presence of considerable amounts of total phenolic (369.75 � 17.9 mg GAE/g) and flavonoid (75.8 � 5.3 mgRE/g) content in the S. cumini extract. The DPPH assay demonstrated a higher antioxidant potential (IC-50 value of 133 ?g/ml), which was comparable to the IC-50 of ascorbic acid (122.4 ?g/ml). Moreover, the S. cumini extract showed a dose dependent cytoprotective effect against H2O2 treated bone marrow mesenchymal stem cells (BM-MSCs). S. cumini also possesses significant anticoagulant activity with a prothrombin time of 28.3 � 1.8 seconds vs 15.8 � 0.2 seconds of control, p