Levofloxacin loaded poly (ethylene oxide)-chitosan/quercetin loaded poly (D,L-lactide-co-glycolide) core-shell electrospun nanofibers for burn wound healing.

This study developed a new burn wound dressing based on core-shell nanofibers that co-deliver antibiotic and antioxidant drugs. For this purpose, poly(ethylene oxide) (PEO)-chitosan (CS)/poly(D,L-lactide-co-glycolide) (PLGA) core-shell nanofibers were fabricated through co-axial electrospinning technique. Antibiotic levofloxacin (LEV) and antioxidant quercetin (QS) were incorporated into the core and shell parts of PEO-CS/PLGA nanofibers, respectively. The drugs could bond to the polymer chains through hydrogen bonding, leading to their steady release for 168 h. An in vitro drug release study showed a burst effect followed by sustained release of LEV and QS from the nanofibers due to the Fickian diffusion. The NIH 3T3 fibroblast cell viability of the drug loaded core-shell nanofibers was comparable to that in the control (tissue culture polystyrene) implying biocompatibility of the nanofibers and their cell supportive role. However, there was no significant difference in cell viability between the drug loaded and drug free core-shell nanofibers. According to in vivo experiments, PEO-CS-LEV/PLGA-QS core-shell nanofibers could accelerate the healing process of a burn wound compared to a sterile gauze. Thanks to the synergistic therapeutic effect of LEV and QS, a significantly higher wound closure rate was recorded for the drug loaded core-shell nanofibrous dressing than the drug free nanofibers and control. Conclusively, PEO-CS-LEV/PLGA-QS core-shell nanofibers were shown to be a promising wound healing material that could drive the healing cascade through local co-delivery of LEV and QS to burn wounds.

Bioengineered Smart Nanocarriers for Breast Cancer Treatment: Adorned Carbon-Based Nanocomposites with Silver and Palladium Complexes for Efficient Drug Delivery.

Biocompatible and bioactive carbon-based nanocomposites are ingeniously designed and fabricated with the aim of enhancing drug delivery applicability in breast cancer treatment. Reduced graphene oxide (rGO) and multiwalled carbon nanotubes (MWCNTs) are utilized as nanocarriers for increasing penetrability into cells and the loading capacity. What sets our study apart is the strategic incorporation of the two different complexes of silver (AgL2) and palladium (PdL2) with the carboxamide-based ligand C9H7N3OS (L), which have been synthesized and decorated on nanocarriers alongside doxorubicin (DOX) for stabilizing DOX by π-π interactions and hydrogen bonding. Although DOX is a well-known cancer therapy agent, the efficacy of DOX is hindered owing to drug resistance, poor internalization, and limited site specificity. Aside from stabilizing DOX on nanocarriers, our carbon-based nanocarriers are tailored to act as a precision-guided missile, strategically by adorning with target-sensitive complexes. Based on the literature, carboxamide ligands can connect to overexpressed receptors on cancerous cells and inhibit them from proliferation signaling. Also, the complexes have an antibacterial activity that can control the infection caused by decreasing white blood cells and necrosis of cancerous cells. A high-concentration cytotoxicity assay revealed that decorating PdL2 on a DOX-containing nanocarrier not only increased cytotoxicity to breast cancerous cell lines (MDA-MB-231 and MCF-7) but also revealed higher cell viability on a normal cell line (MCF-10A). The drug release screening results showed that the presence of PdL2 led to 72 h correlate release behavior in acidic and physiological pH profiles, while the AgL2-containing nanocomposite showed an analogue behavior for just 6 h and the release of DOX continued and after about 100 h hit the top.

Targeted pH- and redox-responsive AuS/micelles with low CMC for highly efficient sonodynamic therapy of metastatic breast cancer.

The efficacy of injectable micellar carriers is hindered due to the disassembly of micelles into free surfactants in the body, resulting in their dilution below the critical micelle concentration (CMC). Copolymer micelles were developed to address this issue, containing a superhydrophilic zwitterionic block and a superhydrophobic block with a disulfide bond, which exhibited a CMC lower than conventional micellar carriers. Cleavable copolymers composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) zwitterion and polycaprolactone CHLZW as the shell, with gold nanoparticles as their core, were studied to deliver doxorubicin to tumor cells while reducing the side effect of the free cytotoxic agent. The research focused on the impact of gold nanoparticles present in targeted TMT-micelles core on stability and in vivo bioavailability and sonotoxicity of the nanoparticles, as well as their synergistic effect on targeted chemotherapy. The nanomicelles prepared in this study demonstrated excellent biocompatibility and responsiveness to stimuli. PCL-SS-MPC nanomicelles displayed drug release in response to GSH and pH, resulting in high DOX release at GSH 10 mM and pH 5. Our findings, supported by MTT, flow cytometry, and confocal laser scanning microscopy, demonstrated that AuS-PM-TMTM-DOX micelles effectively induced apoptosis and enhanced cellular uptake in MCF7 and MDA-MB231 cell lines. The cytotoxic effects of AuS-PM-DOX/US on cancer cells were approximately 38 % higher compared to AuS-PM-DOX samples at a concentration of IC50 0.68 nM. This increase in cellular toxicity was primarily attributed to the promotion of apoptosis. The introduction of disulfide linkages in AuSNPs resulted in increased ROS production when exposed to ultrasound stimulation, due to a reduction in GSH levels. Compared to other commercially available nanosensitizers such as titanium dioxide, exposure of AuS-PM to ultrasound radiation (1.0 W/cm, 2 min) significantly enhanced cavitation effects and resulted in 3 to 5 times higher ROS production. Furthermore, laboratory experiments using human breast cancer cells (MDA-MB-231, MCF7) demonstrated that the toxicity of AuS-PM in response to ultrasound waves is dose-dependent. The findings of this study suggest that this formulated nanocarrier holds great potential as a viable treatment option for breast cancer. It can induce apoptosis in cancer cells, reduce tumor size, and display notable therapeutic efficacy.

Applications of Innovation Technologies for Personalized Cancer Medicine: Stem Cells and Gene-Editing Tools.

Personalized medicine is a new approach toward safer and even cheaper treatments with minimal side effects and toxicity. Planning a therapy based on individual properties causes an effective result in a patient's treatment, especially in a complex disease such as cancer. The benefits of personalized medicine include not only early diagnosis with high accuracy but also a more appropriate and effective therapeutic approach based on the unique clinical, genetic, and epigenetic features and biomarker profiles of a specific patient's disease. In order to achieve personalized cancer therapy, understanding cancer biology plays an important role. One of the crucial applications of personalized medicine that has gained consideration more recently due to its capability in developing disease therapy is related to the field of stem cells. We review various applications of pluripotent, somatic, and cancer stem cells in personalized medicine, including targeted cancer therapy, cancer modeling, diagnostics, and drug screening. CRISPR-Cas gene-editing technology is then discussed as a state-of-the-art biotechnological advance with substantial impacts on medical and therapeutic applications. As part of this section, the role of CRISPR-Cas genome editing in recent cancer studies is reviewed as a further example of personalized medicine application.

pH-sensitive bilayer electrospun nanofibers based on ethyl cellulose and Eudragit S-100 as a dual delivery system for treatment of the burn wounds; preparation, characterizations, and in-vitro/in-vivo assessment.

A pH-sensitive bilayer electrospun nanofibrous mat containing both antibiotic (gentamicin sulfate, GEN) and non-steroidal anti-inflammatory (diclofenac sodium, DIC) drugs was fabricated for burn wound dressing by electrospinning technique, in which ethyl cellulose (EC) and ethyl cellulose/Eudragit S-100 (EC/ES-100) formed the top and bottom layers, respectively. The fabricated pH-sensitive bilayer electrospun nanofibrous mats were characterized from aspects of both structure and efficiency. Physicochemical properties were investigated via SEM, FTIR, and TGA. The swelling ratio and in vitro drug release of the fabricated nanofibrous mats were studied in different pHs. MTT was applied to assess the safety of the fiber mats. Finally, the in vivo efficiency of the designed pH-sensitive bilayer electrospun nanofibrous mats was examined on the male Wistar rats. Based on the histological analysis and wound healing test (in vivo animal experiments), the (ES100/EC-DIC/GEN)-(EC) pH-sensitive bilayer nanofibrous mat displayed faster wound healing than other bilayer nanofibrous mat. As a result, (ES100/EC-DIC/GEN)-(EC) bilayer nanofibrous mat with pH-responsion could accelerate the burn wound healing process via decreasing the adverse effects of GEN and DIC as topical antimicrobial and anti-inflammatory agents, receptively.

Engineered Biomimetic Membranes for Organ-on-a-Chip.

Organ-on-a-chip (OOC) systems are engineered nanobiosystems to mimic the physiochemical environment of a specific organ in the body. Among various components of OOC systems, biomimetic membranes have been regarded as one of the most important key components to develop controllable biomimetic bioanalysis systems. Here, we review the preparation and characterization of biomimetic membranes in comparison with the features of the extracellular matrix. After that, we review and discuss the latest applications of engineered biomimetic membranes to fabricate various organs on a chip, such as liver, kidney, intestine, lung, skin, heart, vasculature and blood vessels, brain, and multiorgans with perspectives for further biomedical applications.

Dual drug delivery system based on layered double hydroxides/carboxymethyl cellulose-poly ethylene oxide bionanocomposite electrospun fibrous mats: Fabrication, characterization, in-vitro and in-vivo studies.

The main goal of the present project was to design and develop ibuprofen (IBU) and layered double hydroxides-vancomycin (LDH-VAN) nanohybrid loaded bionanocomposite fibrous mats to increase the wound healing rate. Thus, first, LDH-VAN nanohybrid particles was synthesized by in-situ incorporation of VAN into the Mg-Al-LDH interlayers during the co-precipitation of hydroxides. Then, LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats were fabricated by electrospinning technique. Test samples were examined XRD, SEM, TEM, TGA, and FTIR. In vitro drug release test was performed in the phosphate buffer solution (pH = 7.4) to prove the efficiency of the fabricated bionanocomposite fibrous mats as a sustained-release carrier for both VAN and IBU. All the fabricated bionanocomposite fibrous mats did not displayed any significant cytotoxicity on NIH/3 T3 fibroblast cells. The wound area in the rats treated with LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats was less than other treatment groups. Based on histological analysis, the LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats possess a faster wound healing than other nanofibrous mats. Data obtained from the present project indicated that LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats could accelerate the wound healing process.

Bioengineering of CuO porous (nano)particles: role of surface amination in biological, antibacterial, and photocatalytic activity.

Nanotechnology is one of the most impressive sciences in the twenty-first century. Not surprisingly, nanoparticles/nanomaterials have been widely deployed given their multifunctional attributes and ease of preparation via environmentally friendly, cost-effective, and simple methods. Although there are assorted optimized preparative methods for synthesizing the nanoparticles, the main challenge is to find a comprehensive method that has multifaceted properties. The goal of this study has been to synthesize aminated (nano)particles via the Rosmarinus officinalis leaf extract-mediated copper oxide; this modification leads to the preparation of (nano)particles with promising biological and photocatalytic applications. The synthesized NPs have been fully characterized, and biological activity was evaluated in antibacterial assessment against Bacillus cereus as a model Gram-positive and Pseudomonas aeruginosa as a model Gram-negative bacterium. The bio-synthesized copper oxide (nano)particles were screened by MTT assay by applying the HEK-293 cell line. The aminated (nano)particles have shown lower cytotoxicity (~ 21%), higher (~ 50%) antibacterial activity, and a considerable increase in zeta potential value (~ + 13.4 mV). The prepared (nano)particles also revealed considerable photocatalytic activity compared to other studies wherein the dye degradation process attained 97.4% promising efficiency in only 80 min and just 7% degradation after 80 min under dark conditions. The biosynthesized copper oxide (CuO) (nano)particle's biomedical investigation underscores an eco-friendly synthesis of (nano)particles, their noticeable stability in the green reaction media, and impressive biological activity.

Montmorillonite-Famotidine/Chitosan Bio-nanocomposite Hydrogels as a Mucoadhesive/Gastroretentive Drug Delivery System.

The main purpose of the present study was to fabricate mucoadhesive bio-nanocomposite hydrogels to prolong the drug retention time in the stomach. In these bio-nanocomposite hydrogels, chitosan (CH) was used as a bioadhesive matrix, montmorillonite (MMT) was applied to modulate the release rate, and tripolyphosphate (TPP) was the cross-linking agent. The test samples were analyzed via different methods such as X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). Drug incorporation efficacy and mucoadhesive strength of these nanocomposite hydrogel beads were studied. Swelling and in vitro drug release behaviors of these bio-nanocomposite hydrogels were evaluated in simulated gastric fluid (SGF; pH 1.2). The optimized MMT-famotidine (FMT)/CH bio-nanocomposite hydrogels displayed a controllable and sustainable drug release profile with suitable mucoadhesion and prolonged retention time in the stomach. Thus, the results demonstrated that the fabricated mucoadhesive bio-nanocomposite hydrogels could remarkably increase the therapeutic efficacy and bioavailability of FMT by the oral route.

A review on computer-aided chemogenomics and drug repositioning for rational COVID-19 drug discovery.

Application of materials capable of energy harvesting to increase the efficiency and environmental adaptability is sometimes reflected in the ability of discovery of some traces in an environment-either experimentally or computationally-to enlarge practical application window. The emergence of computational methods, particularly computer-aided drug discovery (CADD), provides ample opportunities for the rapid discovery and development of unprecedented drugs. The expensive and time-consuming process of traditional drug discovery is no longer feasible, for nowadays the identification of potential drug candidates is much easier for therapeutic targets through elaborate in silico approaches, allowing the prediction of the toxicity of drugs, such as drug repositioning (DR) and chemical genomics (chemogenomics). Coronaviruses (CoVs) are cross-species viruses that are able to spread expeditiously from the into new host species, which in turn cause epidemic diseases. In this sense, this review furnishes an outline of computational strategies and their applications in drug discovery. A special focus is placed on chemogenomics and DR as unique and emerging system-based disciplines on CoV drug and target discovery to model protein networks against a library of compounds. Furthermore, to demonstrate the special advantages of CADD methods in rapidly finding a drug for this deadly virus, numerous examples of the recent achievements grounded on molecular docking, chemogenomics, and DR are reported, analyzed, and interpreted in detail. It is believed that the outcome of this review assists developers of energy harvesting materials and systems for detection of future unexpected kinds of CoVs or other variants.

Biomedical engineering of polysaccharide-based tissue adhesives: Recent advances and future direction.

Tissue adhesives have been widely used for preventing wound leaks, sever bleeding, as well as for enhancing drug delivery and biosensing. However, only a few among suggested platforms cover the circumstances required for high-adhesion strength and biocompatibility, without toxicity. Antibacterial properties, controllable degradation, encapsulation capacity, detectability by image-guided procedures and affordable price are also centered to on-demand tissue adhesives. Herein we overview the history of tissue adhesives, different types of polysaccharide-based tissue adhesives, their mechanism of gluing, and different applications of polysaccharide-based tissue adhesives. We also highlight the latest progresses in engineering of tissue adhesives followed by existing challenges in fabrication processes. We argue that future studies have to place focus on a holistic understanding of biomaterials and tissue surface properties, proper fabrication procedures, and development of magnetic and conductive responsive adhesives in order to bridge the huge gap between the present studies for clinical implementation.

3D printing of bioactive materials for drug delivery applications.

INTRODUCTION: Three-dimensional (3D) printing, also known as additive manufacturing (AM), is a modern technique/technology, which makes it possible to construct 3D objects from computer-aided design (CAD) digital models. This technology can be used in the progress of drug delivery systems, where porosity has played important role in attaining an acceptable level of biocompatibility and biodegradability with improved therapeutic effects. 3D printing may also provide the user possibility to control the dosage of each ingredient in order to a specific purpose, and makes it probable to improve the formulation of drug delivery systems. AREAS COVERED: This article covers the 3D printing technologies, bioactive materials including natural and synthetic polymers as well as some ceramics and minerals and their roles in drug delivery systems. EXPERT OPINION: This technology is feasible to fabricate drug products by incorporating multiple drugs in different parts in such a mode that these drugs can release from the section at a predetermined rate. Furthermore, this 3D printing technology has the potential to transform personalized therapy to various age-groups by design flexibility and precise dosing. In recent years, the potential use of this technology can be realized in a clinical situation where patients will acquire individualized medicine as per their requirement.

Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer.

Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer.

CaZnO-based nanoghosts for the detection of ssDNA, pCRISPR and recombinant SARS-CoV-2 spike antigen and targeted delivery of doxorubicin.

Overexpression of proteins/antigens and other gene-related sequences in the bodies could lead to significant mutations and refractory diseases. Detection and identification of assorted trace concentrations of such proteins/antigens and/or gene-related sequences remain challenging, affecting different pathogens and making viruses stronger. Correspondingly, coronavirus (SARS-CoV-2) mutations/alterations and spread could lead to overexpression of ssDNA and the related antigens in the population and brisk activity in gene-editing technologies in the treatment/detection may lead to the presence of pCRISPR in the blood. Therefore, the detection and evaluation of their trace concentrations are of critical importance. CaZnO-based nanoghosts (NGs) were synthesized with the assistance of a high-gravity technique at a 1,800 MHz field, capitalizing on the use of Rosmarinus officinalis leaf extract as the templating agent. A complete chemical, physical and biological investigation revealed that the synthesized NGs presented similar morphological features to the mesenchymal stem cells (MSCs), resulting in excellent biocompatibility, interaction with ssDNA- and/or pCRISPR-surface, through various chemical and physical mechanisms. This comprise the unprecedented synthesis of a fully inorganic nanostructure with behavior that is similar to MSCs. Furthermore, the endowed exceptional ability of inorganic NGs for detective sensing/folding of ssDNA and pCRISPR and recombinant SARS-CoV-2 spike antigen (RSCSA), along with in-situ hydrogen peroxide detection on the HEK-293 and HeLa cell lines, was discerned. On average, they displayed a high drug loading capacity of 55%, and the acceptable internalizations inside the HT-29 cell lines affirmed the anticipated MSCs-like behavior of these inorganic-NGs.

MIL-125-based nanocarrier decorated with Palladium complex for targeted drug delivery.

The aim of this work was to provide a novel approach to designing and synthesizing a nanocomposite with significant biocompatibility, biodegradability, and stability in biological microenvironments. Hence, the porous ultra-low-density materials, metal-organic frameworks (MOFs), have been considered and the MIL-125(Ti) has been chosen due to its distinctive characteristics such as great biocompatibility and good biodegradability immobilized on the surface of the reduced graphene oxide (rGO). Based on the results, the presence of transition metal complexes next to the drug not only can reinforce the stability of the drug on the structure by preparing π-π interaction between ligands and the drug but also can enhance the efficiency of the drug by preventing the spontaneous release. The effect of utilizing transition metal complex beside drug (Doxorubicin (DOX)) on the drug loading, drug release, and antibacterial activity of prepared nanocomposites on the P. aeruginosa and S. aureus as a model bacterium has been investigated and the results revealed that this theory leads to increasing about 200% in antibacterial activity. In addition, uptake, the release of the drug, and relative cell viabilities (in vitro and in vivo) of prepared nanomaterials and biomaterials have been discussed. Based on collected data, the median size of prepared nanocomposites was 156.2 nm, and their biological stability in PBS and DMEM + 10% FBS was screened and revealed that after 2.880 min, the nanocomposite's size reached 242.3 and 516 nm respectively. The MTT results demonstrated that immobilizing PdL beside DOX leads to an increase of more than 15% in the cell viability. It is noticeable that the AST:ALT result of prepared nanocomposite was under 1.5.

Transferrin receptor-mediated liposomal drug delivery: recent trends in targeted therapy of cancer.

INTRODUCTION: Compared to normal cells, malignant cancer cells require more iron for their growth and rapid proliferation, which can be supplied by a high expression level of transferrin receptor (TfR). It is well known that the expression of TfR on the tumor cells is considerably higher than that of normal cells, which makes TfR an attractive target in cancer therapy. AREAS COVERED: In this review, the primary focus is on the role of TfR as a valuable tool for cancer-targeted drug delivery, followed by the full coverage of available TfR ligands and their conjugation chemistry to the surface of liposomes. Finally, the most recent studies investigating the potential of TfR-targeted liposomes as promising drug delivery vehicles to different cancer cells are highlighted with emphasis on their improvement possibilities to become a part of future cancer medicines. EXPERT OPINION: Liposomes as a valuable class of nanocarriers have gained much attention toward cancer therapy. From all the studies that have exploited the therapeutic and diagnostic potential of TfR on cancer cells, it can be realized that the systematic assessment of TfR ligands applied for liposomal targeted delivery has yet to be entirely accomplished.

Designing a new alginate-fibrinogen biomaterial composite hydrogel for wound healing.

Wound healing is a complex process and rapid healing necessitates a proper micro-environment. Therefore, design and fabrication of an efficacious wound dressing is an impressive innovation in the field of wound healing. The fabricated wound dressing in this scenario was designed using a combination of the appropriate coagulating and anti-bacterial materials like fibrinogen (as coagulating agent), nisin (as anti-bacterial agent), ethylenediaminetetraacetic acid (as anti-bacterial agent), and alginate (as wound healing agent). Biophysical characterization showed that the interaction of fibrinogen and alginate was associated with minor changes in the secondary structure of the protein. Conformational studies showed that the protein was structurally stable at 42 °C, is the maximum temperature of the infected wound. The properties of the hydrogel such as swelling, mechanical resistance, nisin release, antibacterial activity, cytotoxicity, gel porosity, and blood coagulation were assessed. The results showed a slow release for the nisin during 48 h. Antibacterial studies showed an inhibitory effect on the growth of Gram-negative and Gram-positive bacteria. The hydrogel was also capable to absorb a considerable amount of water and provide oxygenation as well as incorporation of the drug into its structure due to its sufficient porosity. Scanning electron microscopy showed pore sizes of about 14-198 µm in the hydrogel. Cell viability studies indicated high biocompatibility of the hydrogel. Blood coagulation test also confirmed the effectiveness of the synthesized hydrogel in accelerating the process of blood clot formation. In vivo studies showed higher rates of wound healing, re-epithelialization, and collagen deposition. According to the findings from in vitro as well as in vivo studies, the designed hydrogel can be considered as a novel attractive wound dressing after further prerequisite assessments.

Recent Developments of Nanostructures for the Ocular Delivery of Natural Compounds.

Ocular disorders comprising various diseases of the anterior and posterior segments are considered as the main reasons for blindness. Natural products have been identified as potential treatments for ocular diseases due to their anti-oxidative, antiangiogenic, and anti-inflammatory effects. Unfortunately, most of these beneficial compounds are characterised by low solubility which results in low bioavailability and rapid systemic clearance thus requiring frequent administration or requiring high doses, which hinders their therapeutic applications. Additionally, the therapeutic efficiency of ocular drug delivery as a popular route of drug administration for the treatment of ocular diseases is restricted by various anatomical and physiological barriers. Recently, nanotechnology-based strategies including polymeric nanoparticles, micelles, nanofibers, dendrimers, lipid nanoparticles, liposomes, and niosomes have emerged as promising approaches to overcome limitations and enhance ocular drug bioavailability by effective delivery to the target sites. This review provides an overview of nano-drug delivery systems of natural compounds such as thymoquinone, catechin, epigallocatechin gallate, curcumin, berberine, pilocarpine, genistein, resveratrol, quercetin, naringenin, lutein, kaempferol, baicalin, and tetrandrine for ocular applications. This approach involves increasing drug concentration in the carriers to enhance drug movement into and through the ocular barriers.