A Comprehensive Review of Hydrogel-Based Drug Delivery Systems: Classification, Properties, Recent Trends, and Applications.

As adaptable biomaterials, hydrogels have shown great promise in several industries, which include the delivery of drugs, engineering of tissues, biosensing, and regenerative medicine. These hydrophilic polymer three-dimensional networks have special qualities like increased content of water, soft, flexible nature, as well as biocompatibility, which makes it excellent candidates for simulating the extracellular matrix and promoting cell development and tissue regeneration. With an emphasis on their design concepts, synthesis processes, and characterization procedures, this review paper offers a thorough overview of hydrogels. It covers the various hydrogel material types, such as natural polymers, synthetic polymers, and hybrid hydrogels, as well as their unique characteristics and uses. The improvements in hydrogel-based platforms for controlled drug delivery are examined. It also looks at recent advances in bioprinting methods that use hydrogels to create intricate tissue constructions with exquisite spatial control. The performance of hydrogels is explored through several variables, including mechanical properties, degradation behaviour, and biological interactions, with a focus on the significance of customizing hydrogel qualities for particular applications. This review paper also offers insights into future directions in hydrogel research, including those that promise to advance the discipline, such as stimuli-responsive hydrogels, self-healing hydrogels, and bioactive hydrogels. Generally, the objective of this review paper is to provide readers with a detailed grasp of hydrogels and all of their potential uses, making it an invaluable tool for scientists and researchers studying biomaterials and tissue engineering.

Recapitulating Antioxidant and Antibacterial Compounds into a Package for Tissue Regeneration: Dual Function Materials with Synergistic Effect.

Oxidative damage and infection can prevent or delay tissue repair. Moreover, infection reinforces reactive oxygen species (ROS) formation, which makes the wound's condition even worse. Therefore, the need for antioxidant and antibacterial agents is felt for tissue regeneration. There are emerging up-and-coming biomaterials that recapitulate both properties into a package, offering an effective solution to turn the wound back into a healing state. In this article, the principles of antioxidant and antibacterial activity are summarized. The review starts with biological aspects, getting the readers to familiarize themselves with tissue barriers against infection. This is followed by the chemistry and mechanism of action of antioxidant and antibacterial materials (dual function). Eventually, the outlook and challenges are underlined to provide where the dual-function biomaterials are and where they are going in the future. It is expected that the present article inspires the designing of dual-function biomaterials to more advanced levels by providing the fundamentals and comparative points of view and paving the clinical way for these materials.

Nano-invasomes for simultaneous topical delivery of buprenorphine and bupivacaine for dermal analgesia.

Opioid and local anaesthetic receptors are abundantly concentrated in different layers of the skin. Therefore, simultaneous targeting of these receptors can produce more potent dermal anaesthesia. Herein, we developed lipid-based nanovesicles for the co-delivery of buprenorphine and bupivacaine to efficiently target skin-concentrated pain receptors. Invasomes incorporating two drugs were prepared by ethanol injection method. Subsequently, the size, zeta potential, encapsulation efficiency, morphology, and in-vitro drug release of vesicles were characterized. Ex-vivo penetration features of vesicles were then investigated by the franz diffusion cell on the full-thickness human skin. Wherein, it was demonstrated that invasomes penetrated the skin deeper and delivered bupivacaine more effectively than buprenorphine to the target site. The superiority of invasome penetration was further evidenced by the results of ex-vivo fluorescent dye tracking. Estimation of in-vivo pain responses by the tail-flick test revealed that compared with the liposomal group, the group receiving invasomal formulation and drug-free invasomal formulation (only containing menthol) displayed increased analgesia in the initial times of 5 and 10 min. Also, no signs of oedema or erythema were observed in the Daze test in any of the rats receiving the invasome formulation. Finally, ex-vivo and in-vivo assays demonstrated efficiency in delivering both drugs into deeper layers of skin and exposing them to the located pain receptors, which improves the time of onset and the analgesic effects. Hence, this formulation appears to be a promising candidate for tremendous development in the clinical setting.

Rosacea Topical Treatment and Care: From Traditional to New Drug Delivery Systems.

Rosacea is a multifactorial chronic inflammatory dermatosis characterized by flushing, nontransient erythema, papules and pustules, telangiectasia, and phymatous alterations accompanied by itching, burning, or stinging, the pathophysiology of which is not yet fully understood. Conventional topical treatments usually show limited efficacy due to the physical barrier property of the skin that hinders skin penetration of the active ingredients, thereby hampering proper drug skin delivery and the respective therapeutic or cosmetic effects. New advances regarding the physiopathological understanding of the disease and the underlying mechanisms suggest the potential of new active ingredients as promising therapeutic and cosmetic approaches to this dermatosis. Additionally, the development of new drug delivery systems for skin delivery, particularly the potential of nanoparticles for the topical treatment and care of rosacea, has been described. Emphasis has been placed on their reduced nanometric size, which contributes to a significant improvement in the attainment of targeted skin drug delivery. In addition to the exposition of the known pathophysiology, epidemiology, diagnosis, and preventive measures, this Review covers the topical approaches used in the control of rosacea, including skin care, cosmetics, and topical therapies, as well as the future perspectives on these strategies.

Electroconductive bioplatform based on dextrin for the immobilization of hemoglobin: Application for electrochemical monitoring of H2O2.

A novel biodegradable dextrin-based nanocomposite, involving polypyrrole (PPy) and hydrophilic dextrin (Dex) (PPy@Dex) was prepared using in-situ radical chemical polymerization technique. The obtained PPy@Dex bionanocomposite was fully characterized by FT-IR, XRD, FESEM, and DSC methods. The exceptional properties such as biocompatibility, high surface area, the proper functional group on the surface, and outstanding electrical conductivity of synthesized bionanocomposite made it a superior candidate over biomolecules immobilization. Electrochemical observations revealed that the PPy@Dex-coated glassy carbon electrode (GCE) demonstrated improved performance, making it a suitable substrate for immobilizing hemoglobin (Hb) and constructing an efficient biosensor. The resulting biosensor, named Hb-PPy@Dex/GCE, exhibited high activity in the reduction of hydrogen peroxide (H2O2). Amperometric examinations demonstrated an extensive linear range from 2 to 350 µM for Hb-PPy@Dex/GCE. The detection limit of the proposed approach was calculated to be 0.54 µM, following the S/N = 3 protocol.

Nanostructures for prevention, diagnosis, and treatment of viral respiratory infections: from influenza virus to SARS-CoV-2 variants.

Viruses are a major cause of mortality and socio-economic downfall despite the plethora of biopharmaceuticals designed for their eradication. Conventional antiviral therapies are often ineffective. Live-attenuated vaccines can pose a safety risk due to the possibility of pathogen reversion, whereas inactivated viral vaccines and subunit vaccines do not generate robust and sustained immune responses. Recent studies have demonstrated the potential of strategies that combine nanotechnology concepts with the diagnosis, prevention, and treatment of viral infectious diseases. The present review provides a comprehensive introduction to the different strains of viruses involved in respiratory diseases and presents an overview of recent advances in the diagnosis and treatment of viral infections based on nanotechnology concepts and applications. Discussions in diagnostic/therapeutic nanotechnology-based approaches will be focused on H1N1 influenza, respiratory syncytial virus, human parainfluenza virus type 3 infections, as well as COVID-19 infections caused by the SARS-CoV-2 virus Delta variant and new emerging Omicron variant.

Chitosan Nanoparticles-Based Cancer Drug Delivery: Application and Challenges.

Chitin is the second most abundant biopolymer consisting of N-acetylglucosamine units and is primarily derived from the shells of marine crustaceans and the cell walls of organisms (such as bacteria, fungi, and algae). Being a biopolymer, its materialistic properties, such as biodegradability, and biocompatibility, make it a suitable choice for biomedical applications. Similarly, its deacetylated derivative, chitosan, exhibits similar biocompatibility and biodegradability properties, making it a suitable support material for biomedical applications. Furthermore, it has intrinsic material properties such as antioxidant, antibacterial, and antitumor. Population studies have projected nearly 12 million cancer patients across the globe, where most will be suffering from solid tumors. One of the shortcomings of potent anticancer drugs is finding a suitable cellular delivery material or system. Therefore, identifying new drug carriers to achieve effective anticancer therapy is becoming essential. This paper focuses on the strategies implemented using chitin and chitosan biopolymers in drug delivery for cancer treatment.

Chronic Inflammation's Transformation to Cancer: A Nanotherapeutic Paradigm.

The body's normal immune response against any invading pathogen that causes infection in the body results in inflammation. The sudden transformation in inflammation leads to the rise of inflammatory diseases such as chronic inflammatory bowel disease, autoimmune disorders, and colorectal cancer (different types of cancer develop at the site of chronic infection and inflammation). Inflammation results in two ways: short-term inflammation i.e., non-specific, involves the action of various immune cells; the other results in long-term reactions lasting for months or years. It is specific and causes angiogenesis, fibrosis, tissue destruction, and cancer progression at the site of inflammation. Cancer progression relies on the interaction between the host microenvironment and tumor cells along with the inflammatory responses, fibroblast, and vascular cells. The two pathways that have been identified connecting inflammation and cancer are the extrinsic and intrinsic pathways. Both have their own specific role in linking inflammation to cancer, involving various transcription factors such as Nuclear factor kappa B, Activator of transcription, Single transducer, and Hypoxia-inducible factor, which in turn regulates the inflammatory responses via Soluble mediators cytokines (such as Interleukin-6, Hematopoietin-1/Erythropoietin, and tumor necrosis factor), chemokines (such as Cyclooxygenase-2, C-X-C Motif chemokines ligand-8, and IL-8), inflammatory cells, cellular components (such as suppressor cells derived from myeloid, tumor-associated macrophage, and acidophils), and promotes tumorigenesis. The treatment of these chronic inflammatory diseases is challenging and needs early detection and diagnosis. Nanotechnology is a booming field nowadays for its rapid action and easy penetration inside the infected destined cells. Nanoparticles are widely classified into different categories based on their different factors and properties such as size, shape, cytotoxicity, and others. Nanoparticles emerged as excellent with highly progressive medical inventions to cure diseases such as cancer, inflammatory diseases, and others. Nanoparticles have shown higher binding capacity with the biomolecules in inflammation reduction and lowers the oxidative stress inside tissue/cells. In this review, we have overall discussed inflammatory pathways that link inflammation to cancer, major inflammatory diseases, and the potent action of nanoparticles in chronic inflammation-related diseases.

Spondias sp: Shedding Light on Its Vast Pharmaceutical Potential.

Many plants are used by the population through popular knowledge passed from generation to generation for the treatment of various diseases. However, there is not always any scientific content supporting these uses, which is very important for safety. One of these plants is the fruit of the Spondias genus, which during its processing generates various residues that are discarded, but which also have pharmacological properties. The focus of this review is to survey the pharmacological activities that Spondias genus shows, as well as which part of the plant is used, since there is a lot of richness in its by-products, such as leaf, bark, resin, seed, and peel, which are discarded and could be reused. The main activities of this genus are antioxidant, anti-inflammatory, antidiabetic, antifungal, and antiviral, among others. These properties indicate that this genus could be used in the treatment of several diseases, but there are still not many products available on the market that use this genus as an active ingredient.

Ethosomes as Nanocarriers for the Development of Skin Delivery Formulations.

The use of nanotechnology has been extensively explored for developing efficient drug delivery systems towards topical and transdermal applications. Ethosomes constitute a vesicular nanocarrier containing a relatively high concentration of ethanol (20-45%). Ethanol is a well-known permeation enhancer, which confers ethosomes unique features, including high elasticity and deformability, allowing them to penetrate deeply across the skin and enhance drug permeation and deposition. The improved composition of ethosomes offer, thereby, significant advantages in the delivery of therapeutic agents over particularly the conventional liposomes regarding different pathologies, including acne, psoriasis, alopecia, skin infections, hormonal deficiencies, among others. This review provides a comprehensive overview of the ethosomal system and an assessment of its potential as an efficient nanocarrier towards the skin delivery of active ingredients. Special attention is given to the composition of ethosomes and the mechanism of skin permeation, as well as their potential applications in different pathologies, particularly skin pathologies (acne, psoriasis, atopic dermatitis, skin cancer and skin infections). Some examples of ethosome-based formulations for the management of skin disorders are also highlighted. Besides the need for further studies, particularly in humans, ethosomal-based formulations hold great promise in the skin delivery of active ingredients, which increasingly asserts oneself as a viable alternative to the oral route.

Prospects of plant-derived exosome-like nanocarriers in oncology and tissue engineering.

Almost all cell types, either in vivo or in vitro, create extracellular vesicles (EVs). Among them are exosomes (EXOs), i.e., tiny nanovesicles containing a lipid bilayer, proteins, and RNAs that are actively involved in cellular communication, indicating that they may be exploited as both diagnostics and therapeutics for conditions like cancer. These nanoparticles can also be used as nanocarriers in many types of research to carry agents such as drugs. Plant-derived exosome-like nanoparticles (PENs) are currently under investigation as a substitute for EXOs formed from mammalian cells, allowing researchers to get beyond the technical constraints of mammalian vesicles. Because of their physiological, chemical, and biological properties, PENs have a lot of promise for use as nanocarriers in drug delivery systems that can deliver various dosages, especially when it comes to large-scale repeatability. The present study has looked at the origins and isolation techniques of PENs, their anticancer properties, their usage as nanocarriers in the treatment of different illnesses, and their antioxidant properties. These nanoparticles can aid in the achievement of therapeutic objectives, as they have benign, non-immunogenic side effects and can pass biological barriers. Time-consuming and perhaps damaging PEN separation techniques is used. For the current PEN separation techniques to be used in commercial and therapeutic settings, they must be altered. In this regard, the concurrent application of biological sciences can be beneficial for improving PEN separation techniques. PENs' innate metabolic properties provide them a great deal of promise for application in drug delivery systems. However, there could be a risk to both the loaded medications and the intrinsic bioactive components if these particles are heavily armed with drugs. Therefore, to prevent these side effects, more studies are needed to devise sophisticated drug-loading procedures and to learn more about the physiology of PENs.

Novel Therapeutic Hybrid Systems Using Hydrogels and Nanotechnology: A Focus on Nanoemulgels for the Treatment of Skin Diseases.

Topical and transdermal drug delivery are advantageous administration routes, especially when treating diseases and conditions with a skin etiology. Nevertheless, conventional dosage forms often lead to low therapeutic efficacy, safety issues, and patient noncompliance. To tackle these issues, novel topical and transdermal platforms involving nanotechnology have been developed. This review focuses on the latest advances regarding the development of nanoemulgels for skin application, encapsulating a wide variety of molecules, including already marketed drugs (miconazole, ketoconazole, fusidic acid, imiquimod, meloxicam), repurposed marketed drugs (atorvastatin, omeprazole, leflunomide), natural-derived compounds (eucalyptol, naringenin, thymoquinone, curcumin, chrysin, brucine, capsaicin), and other synthetic molecules (ebselen, tocotrienols, retinyl palmitate), for wound healing, skin and skin appendage infections, skin inflammatory diseases, skin cancer, neuropathy, or anti-aging purposes. Developed formulations revealed adequate droplet size, PDI, viscosity, spreadability, pH, stability, drug release, and drug permeation and/or retention capacity, having more advantageous characteristics than current marketed formulations. In vitro and/or in vivo studies established the safety and efficacy of the developed formulations, confirming their therapeutic potential, and making them promising platforms for the replacement of current therapies, or as possible adjuvant treatments, which might someday effectively reach the market to help fight highly incident skin or systemic diseases and conditions.

Chitin: A versatile biopolymer-based functional therapy for cartilage regeneration.

Chitin is the second most abundant biopolymer and its inherent biological characteristics make it ideal to use for tissue engineering. For many decades, its properties like non-toxicity, abundant availability, ease of modification, biodegradability, biocompatibility, and anti-microbial activity have made chitin an ideal biopolymer for drug delivery. Research studies have also shown many potential benefits of chitin in the formulation of functional therapy for cartilage regeneration. Chitin and its derivatives can be processed into 2D/3D scaffolds, hydrogels, films, exosomes, and nano-fibers, which make it a versatile and functional biopolymer in tissue engineering. Chitin is a biomimetic polymer that provides targeted delivery of mesenchymal stem cells, especially of chondrocytes at the injected donor sites to accelerate regeneration by enhancing cell proliferation and differentiation. Due to this property, chitin is considered an interesting polymer that has a high potential to provide targeted therapy in the regeneration of cartilage. Our paper presents an overview of the method of extraction, structure, properties, and functional role of this versatile biopolymer in tissue engineering, especially cartilage regeneration.

An Overview of Biosimilars-Development, Quality, Regulatory Issues, and Management in Healthcare.

Biological therapies have transformed high-burden treatments. As the patent and exclusivity period for biological medicines draws to a close, there is a possibility for the development and authorization of biosimilars. These products boast comparable levels of safety, quality, and effectiveness to their precursor reference products. Biosimilars, although similar to reference products, are not identical copies and should not be considered generic substitutes for the original. Their development and evaluation involve a rigorous step-by-step process that includes analytical, functional, and nonclinical evaluations and clinical trials. Clinical studies conducted for biosimilars aim to establish similar efficacy, safety, and immunogenicity, rather than demonstrating a clinical benefit, as with the reference product. However, although the current knowledge regarding biosimilars has significantly increased, several controversies and misconceptions still exist regarding their immunogenicity, extrapolation, interchangeability, substitution, and nomenclature. The development of biosimilars stimulates market competition, contributes toward healthcare sustainability, and allows for greater patient access. However, maximizing the benefits of biosimilars requires cooperation between regulators and developers to ensure that patients can benefit quickly from access to these new therapeutic alternatives while maintaining high standards of quality, safety, and efficacy. Recognizing the inherent complexities of comprehending biosimilars fully, it is essential to focus on realistic approaches, such as fostering open communication between healthcare providers and patients, encouraging informed decision-making, and minimizing risks. This review addresses the regulatory and manufacturing requirements for biosimilars and provides clinicians with relevant insights for informed prescribing.

Gemcitabine-Vitamin E Prodrug-Loaded Micelles for Pancreatic Cancer Therapy.

Pancreatic cancer (PC) is an aggressive cancer subtype presenting unmet clinical challenges. Conventional chemotherapy, which includes antimetabolite gemcitabine (GEM), is seriously undermined by a short half-life, its lack of targeting ability, and systemic toxicity. GEM incorporation in self-assembled nanosystems is still underexplored due to GEM's hydrophilicity which hinders efficient encapsulation. We hypothesized that vitamin E succinate-GEM prodrug (VES-GEM conjugate) combines hydrophobicity and multifunctionalities that can facilitate the development of Pluronic® F68 and Pluronic® F127 micelle-based nanocarriers, improving the therapeutic potential of GEM. Pluronic® F68/VES-GEM and Pluronic® F127/VES-GEM micelles covering a wide range of molar ratios were prepared by solvent evaporation applying different purification methods, and characterized regarding size, charge, polydispersity index, morphology, and encapsulation. Moreover, the effect of sonication and ultrasonication and the influence of a co-surfactant were explored together with drug release, stability, blood compatibility, efficacy against tumour cells, and cell uptake. The VES-GEM conjugate-loaded micelles showed acceptable size and high encapsulation efficiency (>95%) following an excipient reduction rationale. Pluronic® F127/VES-GEM micelles evidenced a superior VES-GEM release profile (cumulative release > 50%, pH = 7.4), stability, cell growth inhibition (<50% cell viability for 100 µM VES-GEM), blood compatibility, and extensive cell internalization, and therefore represent a promising approach to leveraging the efficacy and safety of GEM for PC-targeted therapies.

Nanoemulsions: summary of a decade of research and recent advances.

Nanoemulsions consist of a combination of several components such as oil, water, emulsifiers, surfactants and cosurfactants. Various techniques for producing nanoemulsions include high-energy and low-energy approaches such as high-pressure homogenization, microfluidization, jet disperser and phase inversion methods. The properties of a formulation can be influenced by elements such as the composition, concentration, size and charge of droplets, which in turn can affect the technique of manufacture. Characterization is conducted by the assessment of several factors such as physical properties, pH analysis, viscosity measurement and refractive index determination. This article offers a thorough examination of the latest developments in nanoemulsion technology, with a focus on their wide-ranging applications and promising future possibilities. It also discusses the administration of nanoemulsions through several methods.

A review on natural biopolymers in external drug delivery systems for wound healing and atopic dermatitis.

Despite the advantages of topical administration in the treatment of skin diseases, current marketed preparations face the challenge of the skin's barrier effect, leading to low therapeutic effectiveness and undesirable side effects. Hence, in recent years the management of skin wounds, the main morbidity-causing complication in hospital environments, and atopic dermatitis, the most common inflammatory skin disease, has become a great concern. Fortunately, new, more effective, and safer treatments are already under development, with chitosan, starch, silk fibroin, agarose, hyaluronic acid, alginate, collagen, and gelatin having been used for the development of nanoparticles, liposomes, niosomes and/or hydrogels to improve the delivery of several molecules for the treatment of these diseases. Biocompatibility, biodegradability, increased viscosity, controlled drug delivery, increased drug retention in the epidermis, and overall mitigation of adverse effects, contribute to an effective treatment, additionally providing intrinsic antimicrobial and wound healing properties. In this review, some of the most recent success cases of biopolymer-based drug delivery systems as part of nanocarriers, semi-solid hydrogel matrices, or both (hybrid systems), for the management of skin wounds and atopic dermatitis, are critically discussed, including composition and in vitro, ex vivo and in vivo characterization, showing the promise of these external drug delivery systems.

Harnessing the neuroprotective effect of oral administration of benfotiamine in MPTP induced Parkinson's disease in rats.

The study was performed to evaluate the neuroprotective effects of Benfotiamine (BFT) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) in rats. The rats were given daily doses of BFT (100 mg/kg, 200 mg/kg) through oral administration for 42 days. The rats were given a single bilateral dosage of MPTP (0.1 mg/nostril) intranasally once before the drug treatment to induce PD. On day 42, the animals were subjected to various behavioral paradigms. Post-treatment with BFT for 42 days significantly improved the motor and nonmotor fluctuations of MPTP. The results demonstrated that treatment with BFT ameliorated MPTP-induced disorders in behavior, body balance, and dopamine levels in the mid-brain. Among the post-treated groups, a high dose of BFT was the most effective treatment. Mean values are indicated in ±SEM, n = 5***(p < 0.001) when compared with the vehicle control, n = 5 ### (p < 0.001) when compared with the disease control; (p < 0.001) when compared with the BFT per se; (p < 0.001) when compared with the low dose of BFT; (p < 0.001) when compared with the high dose of BFT. Our finding suggests that BFT contributed to superior antioxidant, and anti-inflammatory and could be a novel therapeutic method for PD management. In conclusion, BFT could be a potential drug candidate for curbing and preventing PD.

Chitosan-based nanosystems for cancer diagnosis and therapy: Stimuli-responsive, immune response, and clinical studies.

Cancer, a global health challenge of utmost severity, necessitates innovative approaches beyond conventional treatments (e.g., surgery, chemotherapy, and radiation therapy). Unfortunately, these approaches frequently fail to achieve comprehensive cancer control, characterized by inefficacy, non-specific drug distribution, and the emergence of adverse side effects. Nanoscale systems based on natural polymers like chitosan have garnered significant attention as promising platforms for cancer diagnosis and therapy owing to chitosan's inherent biocompatibility, biodegradability, nontoxicity, and ease of functionalization. Herein, recent advancements pertaining to the applications of chitosan nanoparticles in cancer imaging and drug/gene delivery are deliberated. The readers are introduced to conventional non-stimuli-responsive and stimuli-responsive chitosan-based nanoplatforms. External triggers like light, heat, and ultrasound and internal stimuli such as pH and redox gradients are highlighted. The utilization of chitosan nanomaterials as contrast agents or scaffolds for multimodal imaging techniques e.g., magnetic resonance, fluorescence, and nuclear imaging is represented. Key applications in targeted chemotherapy, combination therapy, photothermal therapy, and nucleic acid delivery using chitosan nanoformulations are explored for cancer treatment. The immunomodulatory effects of chitosan and its role in impacting the tumor microenvironment are analyzed. Finally, challenges, prospects, and future outlooks regarding the use of chitosan-based nanosystems are discussed.

Treatment avenues for age-related macular degeneration: Breakthroughs and bottlenecks.

Age-related macular degeneration (AMD) is a significant factor contributing to serious vision loss in adults above 50. The presence of posterior segment barriers serves as chief roadblocks in the delivery of drugs to treat AMD. The conventional treatment strategies use is limited due to its off-targeted distribution in the eye, shorter drug residence, poor penetration and bioavailability, fatal side effects, etc. The above-mentioned downside necessitates drug delivery using some cutting-edge technology including diverse nanoparticulate systems and microneedles (MNs) which provide the best therapeutic delivery alternative to treat AMD efficiently. Furthermore, cutting-edge treatment modalities including gene therapy and stem cell therapy can control AMD effectively by reducing the boundaries of conventional therapies with a single dose. This review discusses AMD overview, conventional therapies for AMD and their restrictions, repurposed therapeutics and their anti-AMD activity through different mechanisms, and diverse barriers in drug delivery for AMD. Various nanoparticulate-based approaches including polymeric NPs, lipidic NPs, exosomes, active targeted NPs, stimuli-sensitive NPs, cell membrane-coated NPs, inorganic NPs, and MNs are explained. Gene therapy, stem cell therapy, and therapies in clinical trials to treat AMD are also discussed. Further, bottlenecks of cutting-edge (nanoparticulate) technology-based drug delivery are briefed. In a nutshell, cutting-edge technology-based therapies can be an effective way to treat AMD.