Recent Progress in Chitosan-Based Nanomedicine for Its Ocular Application in Glaucoma

Glaucoma is a degenerative, chronic ocular disease that causes irreversible vision loss. The major symptom of glaucoma is high intraocular pressure, which happens when the flow of aqueous humor between the front and back of the eye is blocked. Glaucoma therapy is challenging because of the low bioavailability of drugs from conventional ocular drug delivery systems such as eye drops, ointments, and gels. The low bioavailability of antiglaucoma agents could be due to the precorneal and corneal barriers as well as the low biopharmaceutical attributes of the drugs. These limitations can be overcome by employing nanoparticulate drug delivery systems. Over the last decade, there has been a lot of interest in chitosan-based nanoparticulate systems to overcome the limitations (such as poor residence time, low corneal permeability, etc.) associated with conventional ocular pharmaceutical products. Therefore, the main aim of the present manuscript is to review the recent research work involving the chitosan-based nanoparticulate system to treat glaucoma. It discusses the significance of the chitosan-based nanoparticulate system, which provides mucoadhesion to improve the residence time of drugs and their ocular bioavailability. Furthermore, different types of chitosan-based nanoparticulate systems are also discussed, namely nanoparticles of chitosan core only, nanoparticles coated with chitosan, and hybrid nanoparticles of chitosan. The manuscript also provides a critical analysis of contemporary research related to the impact of this chitosan-based nanomedicine on the corneal permeability, ocular bioavailability, and therapeutic performance of loaded antiglaucoma agents

Synergistic Effect between Amoxicillin and Zinc Oxide Nanoparticles Reduced by Oak Gall Extract against Helicobacter pylori

Helicobacter pylori (H. pylori) is a global health threat, and the World Health Organization has included H. pylori among 12 bacterial species that require high priority future strategies for the development of new antibiotics due mainly to its high rates of resistance. Metallic nanoparticles are known for their antimicrobial properties. The FDA (Food and Drug Administration) has approved zinc oxide nanoparticles (ZnONPs) as biocompatible antimicrobials. Green synthesis of ZnONPs was performed based on Oak galls extract (OGE) and was characterized by UV, IR, DLS, TEM, and SEM measurements. In addition, LC-MS/MS was used for the identification of OGE constituents. A checkerboard assay was used to evaluate the activity of synthesized Qi-ZnONPs and OGE against H. pylori, and their synergistic effects with amoxicillin were evaluated. LC-MS/MS analyses identified 20 compounds as major gallic acid conjugates. The ZnONPs had average particle sizes of 5.5 nm (DLS) and 7.99 nm (TEM). Both OGE and Qi-ZnONPs exhibited moderate activity against H. pylori. Amoxicillin and Qi-ZnONPs combinations (1:2 and 1:4 amoxicillin:/Qi-ZnONPs) significantly decreased the MIC90 by two-fold and four-fold, respectively, and FIC values for the combinations were more significant than with OGE alone. OGE is rich in phenolics. The synergism between Qi-ZnONPs and amoxicillin can provide an alternative safe agent of low cost to combat H. Pylori infections

Recent Progress in Chitosan-Based Nanomedicine for Its Ocular Application in Glaucoma

Glaucoma is a degenerative, chronic ocular disease that causes irreversible vision loss. The major symptom of glaucoma is high intraocular pressure, which happens when the flow of aqueous humor between the front and back of the eye is blocked. Glaucoma therapy is challenging because of the low bioavailability of drugs from conventional ocular drug delivery systems such as eye drops, ointments, and gels. The low bioavailability of antiglaucoma agents could be due to the precorneal and corneal barriers as well as the low biopharmaceutical attributes of the drugs. These limitations can be overcome by employing nanoparticulate drug delivery systems. Over the last decade, there has been a lot of interest in chitosan-based nanoparticulate systems to overcome the limitations (such as poor residence time, low corneal permeability, etc.) associated with conventional ocular pharmaceutical products. Therefore, the main aim of the present manuscript is to review the recent research work involving the chitosan-based nanoparticulate system to treat glaucoma. It discusses the significance of the chitosan-based nanoparticulate system, which provides mucoadhesion to improve the residence time of drugs and their ocular bioavailability. Furthermore, different types of chitosan-based nanoparticulate systems are also discussed, namely nanoparticles of chitosan core only, nanoparticles coated with chitosan, and hybrid nanoparticles of chitosan. The manuscript also provides a critical analysis of contemporary research related to the impact of this chitosan-based nanomedicine on the corneal permeability, ocular bioavailability, and therapeutic performance of loaded antiglaucoma agents

Synergistic Effect of Mandarin Peels and Hesperidin with Sodium Nitrite against Some Food Pathogen Microbes

Food preservatives such as NaNO2, which are widely used in human food products, undoubtedly affect, to some extent, human organs and health. For this reason, there is a need to reduce the hazards of these chemical preservatives, by replacing them with safe natural bio-preservatives, or adding them to synthetic ones, which provides synergistic and additive effects. The Citrus genus provides a rich source of such bio-preservatives, in addition to the availability of the genus and the low price of citrus fruit crops. In this study, we identify the most abundant flavonoids in citrus fruits (hesperidin) from the polar extract of mandarin peels (agro-waste) by using spectroscopic techniques, as well as limonene from the non-polar portion using GC techniques. Then, we explore the synergistic and additive effects of hesperidin from total mandarin extract with widely used NaNO2 to create a chemical preservative in food products. The results are promising and show a significant synergistic and additive activity. The combination of mandarin peel extract with NaNO2 had synergistic antibacterial activity against B. cereus, Staph. aureus, E. coli, and P. aeruginosa, while hesperidin showed a synergistic effect against B. cereus and P. aeruginosa and an additive effect against Staph. aureus and E. coli. These results refer to the ability of reducing the concentration of NaNO2 and replacing it with a safe natural bio-preservative such as hesperidin from total mandarin extract. Moreover, this led to gaining benefits from their biological and nutritive values

The relationship between hydroxychloroquine plasma concentration and COVID-19 outcomes in rheumatoid arthritis patients in Saudi Arabia

Background: The drug hydroxychloroquine (HCQ) is widely used to treat rheumatoid arthritis (RA) and has been repurposed for the treatment of COVID-19. This study aims to determine whether HCQ concentration levels in individuals with RA alter the incidence of COVID-19 or its complications. Methods: We collected plasma samples from 13 individuals with confirmed rheumatoid arthritis (RA) to measure HCQ concentration levels. The study included individuals at least 18 years old who had been taking HCQ for at least six months at daily doses ranging from 200 to 400 mg. Results: The study enrolled a total of 13 RA patients. All patients were chronic HCQ users. Among the 13 patients, 7 patients were receiving HCQ at a dose of 200 mg per day, and 6 patients were receiving HCQ at a dose of 400 mg per day. COVID-19 confirmed cases accounted for approximately 46% of all patients. Half of the infected patients (n = 3) were taking a daily dose of 200 mg daily, while the other half were taking 400 mg daily. COVID-19 symptoms ranged from mild to moderate, and the intensity of the symptoms was not severe enough to necessitate hospitalization. COVID-19 symptoms in RA patients included headache, fever, fatigue, dry cough, and loss of taste or smell. Conclusions: Our findings indicated that there was no correlation between HCQ concentrations in rheumatoid arthritis patients and the occurrence of COVID-19 or its complications

An Investigation for Skin Tissue Regeneration Enhancement/Augmentation by Curcumin-Loaded Self-Emulsifying Drug Delivery System (SEDDS)

Diabetes, one of the global metabolic disorders, is often associated with delayed wound healing due to the elevated level of free radicals at the wound site, which hampers skin regeneration. This study aimed at developing a curcumin-loaded self-emulsifying drug delivery system (SEDDS) for diabetic wound healing and skin tissue regeneration. For this purpose, various curcumin-loaded SEDDS formulations were prepared and optimized. Then, the SEDDS formulations were characterized by the emulsion droplet size, surface charge, drug content/entrapment efficiency, drug release, and stability. In vitro, the formulations were assessed for the cellular uptake, cytotoxicity, cell migration, and inhibition of the intracellular ROS production in the NIH3T3 fibroblasts. In vivo, the formulations’ wound healing and skin regeneration potential were evaluated on the induced diabetic rats. The results indicated that, after being dispersed in the aqueous medium, the optimized SEDDS formulation was readily emulsified and formed a homogenous dispersion with a droplet size of 37.29 ± 3.47 nm, surface charge of −20.75 ± 0.07 mV, and PDI value of less than 0.3. The drug content in the optimized formulation was found to be 70.51% ± 2.31%, with an encapsulation efficiency of 87.36% ± 0.61%. The SEDDS showed a delayed drug release pattern compared to the pure drug solution, and the drug release rate followed the Fickian diffusion kinetically. In the cell culture, the formulations showed lower cytotoxicity, higher cellular uptake, and increased ROS production inhibition, and promoted the cell migration in the scratch assay compared to the pure drug. The in vivo data indicated that the curcumin-loaded SEDDS-treated diabetic rats had significantly faster-wound healing and re-epithelialization compared with the untreated and pure drug-treated groups. Our findings in this work suggest that the curcumin-loaded SEDDS might have great potential in facilitating diabetic wound healing and skin tissue regeneration

Microwave-Treated Physically Cross-Linked Sodium Alginate and Sodium Carboxymethyl Cellulose Blend Polymer Film for Open Incision Wound Healing in Diabetic Animals—A Novel Perspective for Skin Tissue Regeneration Application

This study aimed at developing the microwave-treated, physically cross-linked polymer blend film, optimizing the microwave treatment time, and testing for physicochemical attributes and wound healing potential in diabetic animals. Microwave-treated and untreated films were prepared by the solution casting method and characterized for various attributes required by a wound healing platform. The optimized formulation was tested for skin regeneration potential in the diabetes-induced open-incision animal model. The results indicated that the optimized polymer film formulation (MB-3) has significantly enhanced physicochemical properties such as high moisture adsorption (154.6 ± 4.23%), decreased the water vapor transmission rate (WVTR) value of (53.0 ± 2.8 g/m2/h) and water vapor permeability (WVP) value (1.74 ± 0.08 g mm/h/m2), delayed erosion (18.69 ± 4.74%), high water uptake, smooth and homogenous surface morphology, higher tensile strength (56.84 ± 1.19 MPa), and increased glass transition temperature and enthalpy (through polymer hydrophilic functional groups depicting efficient cross-linking). The in vivo data on day 16 of post-wounding indicated that the wound healing occurred faster with significantly increased percent re-epithelialization and enhanced collagen deposition with optimized MB-3 film application compared with the untreated group. The study concluded that the microwave-treated polymer blend films have sufficiently enhanced physical properties, making them an effective candidate for ameliorating the diabetic wound healing process and hastening skin tissue regeneration

Systemically Delivered Magnetic Hyperthermia for Prostate Cancer Treatment

Herein, we report a novel therapy for prostate cancer based on systemically delivered magnetic hyperthermia. Conventional magnetic hyperthermia is a form of thermal therapy where magnetic nanoparticles delivered to cancer sites via intratumoral administration produce heat in the presence of an alternating magnetic field (AMF). To employ this therapy for prostate cancer tumors that are challenging to inject intratumorally, we designed novel nanoclusters with enhanced heating efficiency that reach prostate cancer tumors after systemic administration and generate desirable intratumoral temperatures upon exposure to an AMF. Our nanoclusters are based on hydrophobic iron oxide nanoparticles doped with zinc and manganese. To overcome the challenges associated with the poor water solubility of the synthesized nanoparticles, the solvent evaporation approach was employed to encapsulate and cluster them within the hydrophobic core of PEG-PCL (methoxy poly(ethylene glycol)-b-poly(ε-caprolactone))-based polymeric nanoparticles. Animal studies demonstrated that, following intravenous injection into mice bearing prostate cancer grafts, the nanoclusters efficiently accumulated in cancer tumors within several hours and increased the intratumoral temperature above 42 °C upon exposure to an AMF. Finally, the systemically delivered magnetic hyperthermia significantly inhibited prostate cancer growth and did not exhibit any signs of toxicity

Development of a Curcumin-Loaded Lecithin/Chitosan Nanoparticle Utilizing a Box-Behnken Design of Experiment: Formulation Design and Influence of Process Parameters

Curcumin (CUR) has impressive pharmacologic properties, including cardioprotective, neuroprotective, antimicrobial, and anticancer activity. However, the pharmaceutical application of CUR is limited due to its poor aqueous solubility and low bioavailability. The development of novel formulations has attracted considerable attention to the idea of applying nanobiotechnology to improve the therapeutic efficacy of these challenging compounds. In this study, CUR-loaded lecithin–chitosan nanoparticles (CUR/LCSNPs) were developed and optimized by the concentration of chitosan, lecithin, and stirring speed by a 3-factorial Box-Behnken statistical design, resulting in an optimal concentration of chitosan (A) and lecithin (B) with a 1200 rpm stirring speed (C), with applied constraints of minimal average particle size (Y1), optimal zeta potential (Y2), and maximum entrapment efficiency (%EE) (Y3). The mean particle size of the checkpoint formulation ranged from 136.44 ± 1.74 nm to 267.94 ± 3.72, with a zeta potential of 18.5 ± 1.39 mV to 36.8 ± 3.24 mV and %EE of 69.84 ± 1.51% to 78.50 ± 2.11%. The mean particle size, zeta potential, %EE, and % cumulative drug release from the optimized formulation were 138.43 ± 2.09 nm, +18.98 ± 0.72 mV, 77.39 ± 1.70%, and 86.18 ± 1.5%, respectively. In vitro drug release followed the Korsmeyer–Peppas model with Fickian diffusion (n < 0.45). The optimized technique has proven successful, resulting in a nanoformulation that can be used for the high loading and controlled release of lipophilic drugs

Utilization of Nanotechnology to Improve Bone Health in Osteoporosis Exploiting Nigella sativa and Its Active Constituent Thymoquinone

Osteoporosis, a chronic bone disorder, is one of the leading causes of fracture and morbidity risk. Numerous medicinally important herbs have been evaluated for their efficacy in improving bone mass density in exhaustive preclinical and limited clinical studies. Nigella sativa L. has been used as local folk medicine, and traditional healers have used it to manage various ailments. Its reported beneficial effects include controlling bone and joint diseases. The present manuscript aimed to provide a sound discussion on the pharmacological evidence of N. sativa and its active constituent, thymoquinone, for its utility in the effective management of osteoporosis. N. sativa is reported to possess anti-IL-1 and anti-TNF-&alpha;-mediated anti-inflammatory effects, leading to positive effects on bone turnover markers, such as alkaline phosphatase and tartrate-resistant acid phosphatase. It is reported to stimulate bone regeneration by prompting osteoblast proliferation, ossification, and decreasing osteoclast cells. Thymoquinone from N. sativa has exhibited an antioxidant effect on bone tissue by reducing the FeNTA-induced oxidative stress. The present manuscript highlights phytochemistry, pharmacological effect, and the important mechanistic perspective of N. sativa and its active constituents for the management of osteoporosis. Further, it also provides sound discussion on the utilization of a nanotechnology-mediated drug delivery approach as a promising strategy to improve the therapeutic performance of N. sativa and its active constituent, thymoquinone, in the effective management of osteoporosis