We created and evaluated an enhanced topical delivery system featuring a combination of highly skin-permeable growth factors (GFs), quercetin (QCN), and oxygen; these synergistically accelerated re-epithelialization and granulation tissue formation of/in diabetic wounds by increasing the levels of GFs and antioxidants, and the oxygen partial pressure, at the wound site. To enhance the therapeutic effects of exogenous administration of GFs for the treatment of diabetic wounds, we prepared highly skin-permeable GF complexes comprised of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), platelet-derived growth factor-A (PDGF-A), and basic fibroblast growth factor (bFGF), genetically attached, via the N-termini, to a low-molecular-weight protamine (LMWP) to form LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, and LMWP-bFGF, respectively. Furthermore, quercetin (QCN)- and oxygen-carrying 1-bromoperfluorooctane (PFOB)-loaded nanoemulsions (QCN-NE and OXY-PFOB-NE) were developed to improve the topical delivery of QCN and oxygen, respectively. After confirming the enhanced penetration of LMWP-GFs, QCN-NE, and oxygen delivered from OXY-PFOB-NE across human epidermis, we evaluated the effects of combining LMWP-GFs, QCN-NE, and OXY-PFOB-NE on proliferation of keratinocytes and fibroblasts, and the chronic wound closure rate of a diabetic mouse model. The optimal ratios of LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, LMWP-bFGF, QCN-NE, and OXY-PFOB-NE were 1, 1, 0.02, 0.02, 0.2, and 60, respectively. Moreover, a Carbopol hydrogel containing LMWP-GFs, QCN-NE, and OXY-PFOB-NE (LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL) significantly improved scratch-wound recovery of keratinocytes and fibroblasts in vitro compared to that afforded by hydrogels containing each component alone. LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL significantly accelerated wound-healing in a diabetic mouse model, decreasing wound size by 54 and 35% compared to the vehicle and LMWP-GFs, respectively. LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL synergistically accelerated the healing of chronic wounds, exerting both rapid and prolonged effects.

In this study, we report a new multifunctional nanoparticle with antioxidative and antibacterial activities in vitro. ZnO@GA nanoparticles were fabricated by coordinated covalent bonding of the antioxidant gallic acid (GA) on the surface of ZnO nanoparticles. This addition imparts both antioxidant activity and high affinity for the bacterial cell membrane. Antioxidative activities at various concentrations were evaluated using a 2,2′-azino-bis(ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging method. Antibacterial activities were evaluated against Gram-positive bacteria (Staphylococcus aureus: S. aureus), including several strains of methicillin-resistant S. aureus (MRSA), and Gram-negative bacteria (Escherichia coli). The functionalized ZnO@GA nanoparticles showed good antioxidative activity (69.71%), and the bactericidal activity of these nanoparticles was also increased compared to that of non-functionalized ZnO nanoparticles, with particularly effective inhibition and high selectivity for MRSA strains. The results indicate that multifunctional ZnO nanoparticles conjugated to GA molecules via a simple surface modification process displaying both antioxidant and antibacterial activity, suggesting a possibility to use it as an antibacterial agent for removing MRSA.

Dry eye disease is a multifactorial disorder of the eye and tear film with potential damage to the ocular surface. Various treatment approaches for this disorder aim to alleviate disease symptoms and restore the normal ophthalmic environment. The most widely used dosage form is eye drops of different drugs with 5% bioavailability. The use of contact lenses to deliver drugs increases bioavailability by up to 50%. Cyclosporin A is a hydrophobic drug loaded onto contact lenses to treat dry eye disease with significant improvement. The tear is a source of vital biomarkers for various systemic and ocular disorders. Several biomarkers related to dry eye disease have been identified. Contact lens sensing technology has become sufficiently advanced to detect specific biomarkers and predict disease conditions accurately. This review focuses on dry eye disease treatment with cyclosporin A-loaded contact lenses, contact lens biosensors for ocular biomarkers of dry eye disease, and the possibility of integrating sensors in therapeutic contact lenses.

Artificial oxygen carriers have emerged as potential substitutes for red blood cells in situations of major blood loss, including accidents, surgical procedures, trauma, childbirth, stomach ulcers, hemorrhagic shock, and blood vessel ruptures which can lead to sudden reduction in blood volume. The therapeutic delivery of oxygen utilizing artificial oxygen carriers as red blood cell substitutes presents a promising avenue for treating a spectrum of disease models. Apart from that, the recent advancement of artificial oxygen carriers intended to supplant conventional blood transfusions draws significant attention due to the exigencies of warfare and the ongoing challenges posed by the COVID-19 pandemic. However, there is a pressing need to formulate stable, non-toxic, and immunologically inert oxygen carriers. Even though numerous challenges are encountered in the development of artificial oxygen carriers, their applicability extends to various medical treatments, encompassing elective and cardiovascular surgeries, hemorrhagic shock, decompression illness, acute stroke, myocardial infarction, sickle cell crisis, and proficient addressing conditions such as cerebral hypoxia. Therefore, this paper provides an overview of therapeutic oxygen delivery using assorted types of artificial oxygen carriers, including hemoglobin-based, perfluorocarbon-based, stem cell-derived, and oxygen micro/nanobubbles, in the treatment of diverse disease models. Additionally, it discusses the potential side effects and limitations associated with these interventions, while incorporating completed and ongoing research and recent clinical developments. Finally, the prospective solutions and general demands of the perfect artificial oxygen carriers were anticipated to be a reference for subsequent research endeavors.