Biomembrane camouflaged nanoparticles: A paradigm shifts in targeted drug delivery system.

Targeted drug delivery has emerged as a pivotal approach within precision medicine, aiming to optimize therapeutic efficacy while minimizing systemic side effects. Advanced biomimetic membrane-coated formulations have garnered significant interest from researchers as a promising strategy for targeted drug delivery, site-specific accumulation and heightened therapeutic outcomes. Biomimetic nanotechnology is able to retain the biological properties of the parent cell thus are able to exhibit superior targeting compared to conventional formulations. In this review, we have described different types of cell membrane camouflaged NPs. Mechanism of isolation and coating of the membranes along with the applications of each type of membrane and their mechanism to reach the desired site. Furthermore, a fusion of different membranes in order to prepare hybrid membrane biomimetic NPs which could possess better efficacy is discussed in detail in the review. Later, applications of the hybrid membrane-cloaked NPs along with current development were discussed in detail along with the challenges associated with it. Although membrane-cloaked NPs are currently in the preliminary stage of development, there is a huge potential to explore this biodegradable and biocompatible delivery system.

QbD-Assisted Development and Optimization of Doxycycline Hyclate- and Hydroxyapatite-Loaded Nanoparticles for Periodontal Delivery.

The current research aims to develop a carrier system for the delivery of a matrix metalloproteinase (MMP) inhibitor along with a bioceramic agent to the periodontal pocket. It is proposed that the present system, if given along with a systemic antibiotic, would be a fruitful approach for periodontitis amelioration. To fulfill the aforementioned objective, a doxycycline hyclate- and hydroxyapatite-adsorbed composite was prepared by a physical adsorption method and successfully loaded inside sodium alginate-chitosan nanoparticles and optimized based on particle size and drug content. Optimized formulation was then subjected to different evaluation parameters like encapsulation efficiency, hydroxyapatite content, ζ potential, surface morphology, in vitro drug release, cell line studies, and stability studies. For the optimized formulation, particle size, polydispersity index (PDI), entrapment efficiency, ζ potential, and drug content were found to be 336.50 nm, 0.23, 41.77%, -13.85 mV, and 14.00%, respectively. The surface morphology of the placebo and adsorbed composite-loaded nanoparticles as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the spherical shape and rough surface of the particles. In gingival crevicular fluid (GCF) 7.6, a sustained drug release profile was obtained up to 36 h. In vitro % viability studies performed on murine fibroblast cells (NIH3T3) and human periodontal ligament (hPDL) cell lines confirmed the proliferative nature of the formulation. Also, when subjected to stability studies for 4 weeks, particle size, PDI, and drug content did not vary considerably, thereby ensuring the stable nature of nanoparticles. Henceforth, sodium alginate-chitosan nanoparticles appeared to be a good carrier system for doxycycline hyclate and hydroxyapatite for periodontal therapy. If given along with a system antibiotic, the system will serve as a fruitful tool for infection-mediated periodontal regeneration and healing.

Utilization of Quince (Cydonia oblonga) Peel and Exploration of Its Metabolite Profiling and Cardioprotective Potential Against Doxorubicin-Induced Cardiotoxicity in Wistar Rats.

Quince (Cydonia oblonga Mill.) is a pomaceous fruit that is typically processed into jams, jellies, and marmalade. The byproduct, i.e., the quince peel emanated from the processing industry, can be upcycled, ensuring zero waste policy and resulting in a sustainable food system. In our study, the quince peel was explored for in vitro phytochemical analysis and in vivo cardioprotective potential. Two diverse extractions (ultrasonication and reflux) and four different solvents (aqueous, ethanolic, hydroethanolic, and methanolic) were used for the extraction of quince peel and assessed for the phytochemical and antioxidant study. Among all the evaluated extracts, hydroethanolic quince extract extracted through the reflux extraction method showed the maximum phenolic (27.23 ± 0.85 mg GAE/g DW) and flavonoid (16.5 ± 1.02 mg RE/g DW) content. The maximum antioxidant potential (DPPH) with an IC50 value of 204.8 ± 2.24 µg/mL was noted for the hydroethanolic extract. This best active extract was then subjected to HPTLC, UPLC-MS, mineral, and FTIR analysis to study the metabolic profiling and inorganic composition and to confirm the presence of bioactives. Additionally, the in vivo study was done in rats using doxorubicin (DOX)-induced cardiotoxicity. The rats were given extracts orally at 160 and 320 mg/kg bw for 30 days. ECG analysis was done at the termination of the experiment. Besides this, the lipid profile, blood serum parameters (CK-MB, LDH, AST), and tissue parameters (MDA, SOD, GSH, CAT) were analyzed. The DOX-treated group unveiled a substantial variance (p < 0.001) in all the parameters in contrast to the normal control group and extract control groups. However, the pretreated groups substantially alleviated the DOX-induced changes in all the parameters. Additionally, recuperation in histopathological alterations of the cardiac tissue in contrast to the DOX-induced toxicity was also seen in the pretreated groups. Thus, it could be said that the cardioprotective activity of the quince peel extract attributed to the presence of phytoconstituents counteracted the DOX-induced cardiotoxicity and assisted in the restoration of the cardiac injury in rats.

Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches.

Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, treatments available till date including phytocompounds, chemotherapy, radiotherapy, photothermal therapy, surgery, combination therapy, molecular targets associated with cancer growth and metastasis, and special emphasis on nanotechnology-based approaches for downregulating the deleterious disease. A detailed analysis with respect to types of nanoparticles and their scope in overcoming multidrug resistance as well as associated clinical trials has been discussed.

Advanced targeted drug delivery by bioengineered white blood cell-membrane camouflaged nanoparticulate delivery nanostructures.

Targeted drug delivery has emerged as a pivotal approach within precision medicine, aiming to optimize therapeutic efficacy while minimizing systemic side effects. Leukocyte membrane coated nanoparticles (NPs) have attracted a lot of interest as an effective approach for delivering targeted drugs, capitalizing on the natural attributes of leukocytes to achieve site-specific accumulation, and heightened therapeutic outcomes. An overview of the present state of the targeted medication delivery research is given in this review. Notably, Leukocyte membrane-coated NPs offer inherent advantages such as immune evasion, extended circulation half-life, and precise homing to inflamed or diseased tissues through specific interactions with adhesion molecules. leukocyte membrane-coated NPs hold significant promise in advancing targeted drug delivery for precision medicine. As research progresses, they are anticipated to contribute to improved therapeutic outcomes, enabling personalized and effective treatments for a wide range of diseases and conditions. The review covers the method of preparation, characterization, and biological applications of leucocytic membrane coated NPs. Further, patents related factors, gap of translation from laboratory to clinic, and future prospective were discussed in detail. Overall, the review covers extensive literature to establish leucocytic membrane NPs for targeted drug delivery.

A Comprehensive review on Pharmacokinetic Studies of Vaccines: Impact of delivery route, carrier-and its modulation on immune response.

The lack of knowledge about the absorption, distribution, metabolism, and excretion (ADME) of vaccines makes former biopharmaceutical optimization difficult. This was shown during the COVID-19 immunization campaign, where gradual booster doses were introduced.. Thus, understanding vaccine ADME and its effects on immunization effectiveness could result in a more logical vaccine design in terms of formulation, method of administration, and dosing regimens. Herein, we will cover the information available on vaccine pharmacokinetics, impacts of delivery routes and carriers on ADME, utilization and efficiency of nanoparticulate delivery vehicles, impact of dose level and dosing schedule on the therapeutic efficacy of vaccines, intracellular and endosomal trafficking and in vivo fate, perspective on DNA and mRNA vaccines, new generation sequencing and mathematical models to improve cancer vaccination and pharmacology, and the reported toxicological study of COVID-19 vaccines. Altogether, this review will enhance the reader's understanding of the pharmacokinetics of vaccines and methods that can be implied in delivery vehicle design to improve the absorption and distribution of immunizing agents and estimate the appropriate dose to achieve better immunogenic responses and prevent toxicities.

CD44 mediated colon cancer targeting mutlifaceted lignin nanoparticles: Synthesis, in vitro characterization and in vivo efficacy studies.

Hyaluronic acid (HA) coated irinotecan loaded lignin nanoparticles (HDLNPs) were synthesized using ionic interaction method. Optimized nanoparticles were characterized for their active chemotherapeutic targeting potential to CD44 receptors overly-expressed on cancer cells. Blood component interaction studies supported hemocompatible nature of HDLNPs and also demonstrated their sustained plasma residence property. Cell anti-proliferation and mitochondrial depolarization studies on HT-29 cells suggest significantly (p < 0.01) improved chemotherapeutic efficacy of HDLNPs. In vitro cell based studies showed that nanoparticles have retained antioxidant activity of lignin that can prevent cancer relapse. In vivo biodistribution studies in tumor-bearing Balb/c mice confirmed improved drug localization in tumor site for longer duration. Tumor regression and histopathological studies indicated the efficacy ofligand-assisted targeting chemotherapy over the conventional therapy. Hematological and biochemical estimation suggested that irinotecan-associated myelosuppression, liver steatosis and rare kidney failure can be avoided by its encapsulation in HA-coated lignin nanoparticles. HDLNPs were found to be stable over a period of 12 months.

Nanotechnology-empowered strategies in treatment of skin cancer.

In current scenario skin cancer is a serious condition that has a significant impact on world health. Skin cancer is divided into two categories: melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC). Because of its significant psychosocial effects and need for significant investment in new technology and therapies, skin cancer is an illness of global health relevance. From the patient's perspective chemotherapy considered to be the most acceptable form of treatment. However, significant negatives of chemotherapy such as severe toxicities and drug resistance pose serious challenges to the treatment. The field of nanomedicine holds significant promise for enhancing the specificity of targeting neoplastic cells through the facilitation of targeted drug delivery to tumour cells. The integration of multiple therapeutic modalities to selectively address cancer-promoting or cell-maintaining pathways constitutes a fundamental aspect of cancer treatment. The use of mono-therapy remains prevalent in the treatment of various types of cancer, it is widely acknowledged in the academic community that this conventional approach is generally considered to be less efficacious compared to the combination treatment strategy. The employment of combination therapy in cancer treatment has become increasingly widespread due to its ability to produce synergistic anticancer effects, mitigate toxicity associated with drugs, and inhibit multi-drug resistance by means of diverse mechanisms. Nanotechnology based combination therapy represents a promising avenue for the development of efficacious therapies for skin cancer within the context of this endeavour. The objective of this article is to provide a description of distinct challenges for efficient delivery of drugs via skin. This article also provides a summary of the various nanotechnology based combinatorial therapy available for skin cancer with their recent advances. This review also focuses on current status of clinical trials of such therapies.

Advanced multifunctional nano-lipid carrier loaded gel for targeted delivery of 5-flurouracil and cannabidiol against non-melanoma skin cancer.

Non-melanoma skin cancer is one of the most common malignancies reported around the globe. Current treatment therapies fail to meet the desired therapeutic efficacy due to high degree of drug resistance. Thus, there is prominent demand in advancing the current conventional therapy to achieve desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The current investigation has been designed to evaluate the safety and efficacy of developed 5-Flurouracil and cannabidiol loaded combinatorial lipid-based nanocarrier (FU-CBD NLCs) gel for the effective treatment of skin cancer. Initially, confocal microscopy study results showed excellent uptake and deposition at epidermal and the dermal layer. Irritation studies performed by IR camera and HET cam shows FU-CBD NLCs was much more tolerated and less irritant compared to conventional treatment. Furthermore, gamma scintigraphy evaluation shows the skin retention behavior of the formulation. Later, in-ovo tumor remission studies were performed, and it was found that prepared FU-CBD NLCs was able to reduce tumor volume significantly compared to conventional formulation. Thus, obtained results disclosed that permeation and disposition of 5-FU and CBD into different layers of the skin FU-CBD NLCs gel could be more potential carrier than conventional gel. Furthermore, prepared formulation showed greater tumor remission, better survival rate, reduction in tumor number, area, and volume with improved biochemical profile. Thus, prepared gel could serve as a promising formulation approach for the skin cancer treatment.

Dasatinib: a potential tyrosine kinase inhibitor to fight against multiple cancer malignancies.

Dasatinib is the 2nd generation TKI (Tyrosine Kinase Inhibitor) having the potential to treat numerous forms of leukemic and cancer patients and it is 300 times more potent than imatinib. Cancer is the major cause of death globally and need to enumerate novel strategies to coping with it. Various novel therapeutics introduced into the market for ease in treating various forms of cancer. We reviewed and evaluated all the related aspects of dasatinib, which can enhance the knowledge about dasatinib therapeutics methodology, pharmacodynamic and pharmacokinetics, side effects, advantages, disadvantages, various kinds of interactions and its novel formulations as well.

Exploring the Remarkable Chemotherapeutic Potential of Polyphenolic Antioxidants in Battling Various Forms of Cancer.

Plant-derived compounds, specifically antioxidants, have played an important role in scavenging the free radicals present under diseased conditions. The persistent generation of free radicals in the body leads to inflammation and can result in even more severe diseases such as cancer. Notably, the antioxidant potential of various plant-derived compounds prevents and deregulates the formation of radicals by initiating their decomposition. There is a vast literature demonstrating antioxidant compounds' anti-inflammatory, anti-diabetic, and anti-cancer potential. This review describes the molecular mechanism of various flavonoids, such as quercetin, kaempferol, naringenin, epicatechin, and epicatechin gallate, against different cancers. Additionally, the pharmaceutical application of these flavonoids against different cancers using nanotechnologies such as polymeric, lipid-based nanoparticles (solid-lipid and liquid-lipid), liposomes, and metallic nanocarriers is addressed. Finally, combination therapies in which these flavonoids are employed along with other anti-cancer agents are described, indicating the effective therapies for the management of various malignancies.

Formulation and development of novel lipid-based combinatorial advanced nanoformulation for effective treatment of non-melanoma skin cancer.

Non-melanoma skin cancer is one of the most common malignancies reported with high number of morbidities, demanding an advanced treatment option with superior chemotherapeutic effects. Due to high degree of drug resistance, conventional therapy fails to meet the desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The NLCs were optimized using central composite design that showed an average particle size of 206 nm and a zeta potential of -34 mV. In addition, in vitro and ex vivo drug permeations studies demonstrated the effective delivery of both drugs in the skin layers via lipid structured nanocarriers. Also, the prepared FU-CBD-NLCs showed promising effect in-vitro cell studies including MTT assays, wound healing and cell cycle as compared to the conventional formulation. Moreover, dermatokinetic studies shows there was superior deposition of drugs at epidermal and the dermal layer when treated with FU-CBD-NLCs. In the end, overall study offered a novel combinatorial chemotherapy that could be an option for the treatment of non-melanoma skin cancer.

Recent update on electrospinning and electrospun nanofibers: current trends and their applications.

Electrospinning is a versatile and viable technique for generating ultrathin fibers. Remarkable progress has been made in techniques for creating electro-spun and non-electro-spun nanofibers. Nanofibers were the center of attention for industries and researchers due to their simplicity in manufacture and setup. The review discusses a thorough overview of both electrospinning and non-electrospinning processes, including their setup, fabrication process, components, and applications. The review starts with an overview of the field of nanotechnology, the background of electrospinning, the surge in demand for nanofiber production, the materials needed to make nanofibers, and the critical process variables that determine the characteristics of nanofibers. Additionally, the diverse applications of electrospun nanofibers, such as smart mats, catalytic supports, filtration membranes, energy storage/heritage components, electrical devices (batteries), and biomedical scaffolds, are then covered. Further, the review concentrates on the most recent and pertinent developments in nanofibers that are connected to the use of nanofibers, focusing on the most illustrative cases. Finally, challenges and their possible solutions, marketing, and the future prospects of nanofiber development are discussed.

Review on 3D printing in dentistry: conventional to personalized dental care.

The CAD (Computer-aided design) and CAM (computer-aided manufacturing) have most applications in the manufacturing of fully automated, personalized dental devices and tailor-made treatment plans. 3D printing is one of the most rapidly expanding and new methods of manufacturing different things because of its on-demand and high productivity within the cost-effective manner which have a variety of applications in healthcare, pharmaceuticals, orthopaedics, engineered tissue models, medical devices, defence industries, automotive and aerospace sectors. Due to its emerging applications in the various sectors, the healthcare, Industries, and academic sectors are attracted towards the 3D printed materials. This review talks about the dental implants, polymers that are employed in concocting dental implants, critical parameters, and challenges which are to be considered while preparing these implants, advantages of 3D printing in the field of dentistry and the current trends. it discusses the variety of applications of 3D printed materials in the field of dentistry. Along with their method of fabrication, their critical process parameters (CPPs) are also discussed.

Nano Matrix Soft Confectionary for Oral Supplementation of Vitamin D: Stability and Sensory Analysis.

Vitamin D deficiency distresses nearly 50% of the population globally and multiple studies have highlighted the association of Vitamin D with a number of clinical manifestations, including musculoskeletal, cardiovascular, cerebrovascular, and neurological disorders. In the current study, vitamin D oil-in-water (O/W) nanoemulsions were developed and incorporated in edible gummies to enhance bioavailability, stability, and patient compliance. The spontaneous emulsification method was employed to produce a nano-emulsion using corn oil with tween 20 and lecithin as emulsifiers. Optimization was carried out using pseudo-ternary phase diagrams and the average particle size and polydispersity index (PDI) of the optimized nanoemulsion were found to be 118.6 ± 4.3 nm and 0.11 ± 0.30, respectively. HPLC stability analysis demonstrated that the nano-emulsion prevented the degradation and it retained more than 97% of active vitamin D over 15 days compared to 94.5% in oil solution. Similar results were obtained over further storage analysis. Vitamin D gummies based on emulsion-based gelled matrices were then developed using gelatin as hydrocolloid and varying quantities of corn oil. Texture analysis revealed that gummies formulated with 10% corn oil had the optimum hardness of 3095.6 ± 201.7 g on the first day which remained consistent on day 45 with similar values of 3594.4 ± 210.6 g. Sensory evaluation by 19 judges using the nine-point hedonic scale highlighted that the taste and overall acceptance of formulated gummies did not change significantly (p > 0.05) over 45 days storage. This study suggested that nanoemulsions consistently prevent the environmental degradation of vitamin D, already known to offer protection in GI by providing sustained intestinal release and enhancing overall bioavailability. Soft chewable matrices were easy to chew and swallow, and they provided greater patient compliance.

"Nanodecoys" - Future of drug delivery by encapsulating nanoparticles in natural cell membranes.

Biomimetic nanotechnology could serve as an advancement in the domain of drug delivery and diagnosis with the application of natural cell membrane or synthetically-derived membrane nanoparticles (NPs). These biomimetic NPs endow significant therapeutic and diagnostic efficacy by their unique properties, such as immune invasion and better targeting ability. Additionally, these NPs have a unique ability to retain the inherent properties of cell membrane and membrane's intrinsic functionalities, which helps them to exhibit superior therapeutic effects. In this review, we describe how these membrane-clocked NPs endow superior therapeutic effects by immune invasion; along with this, the development of membrane-coated NPs and their method of preparation and characterization has been clearly described in the manuscript. Moreover, Various developed membrane-coated NPs such as red blood cell membrane-coated NPs, white blood cells membrane-coated NPs, platelet membrane coated, cancer cell membrane coated, bacterial membrane vesicles and, mesenchymal stem cells membrane-coated NPs have been established in this manuscript. At last, the discussion on the role of membrane-coated NPs as theranostics, and notably, the literature that demonstrates the shreds of evidences of these NPs in targeting and neutralizing the SARS-CoV-2 virus have also been incorporated.

Intranasal Cerium Oxide Nanoparticles Ameliorate Cognitive Function in Rats with Alzheimer's via Anti-Oxidative Pathway.

Cerium oxide nanoparticles (CNPs), owing to their antioxidant property, have recently emerged as therapeutic candidate for Alzheimer's disease (AD). However, intravenous CNPs are limited due to their poor physicochemical properties, rapid blood clearance and poor blood-brain penetration. Thus, we developed intranasal CNPs and evaluated its potential in experimental AD. CNPs were synthesized using homogenous precipitation method and optimized through Box-Behnken Design. The formation of CNPs was confirmed by UV spectroscopy and FTIR. The optimized CNP were spherical, small (134.0 ± 3.35 nm), uniform (PDI, 0.158 ± 0.0019) and stable (ZP, -21.8 ± 4.94 mV). The presence of Ce in CNPs was confirmed by energy-dispersive X-ray analysis. Further, the X-ray diffraction spectra revealed that the CNPs were nano-crystalline. The DPPH assay showed that at concentration of 50 µg/mL, the percentage radical scavenging was 95.40 ± 0.006%. Results of the in vivo behavioral studies in the scopolamine-induced Alzheimer rat model showed that intranasal CNPs dose dependently reversed cognitive ability. At dose of 6 mg/kg the morris water maze results (escape latency, path length and dwell time) and passive avoidance results (retention latency) were significantly different from untreated group but not significantly different from positive control group (rivastigmine patch, 13.3 mg/24 h). Further, biochemical estimation showed that intranasal CNP upregulated the levels of SOD and GSH in brain. In conclusion, intranasal CNPs, through its antioxidant effect, could be a prospective therapeutics for the treatment of cognitive impairment in AD.

Overcoming Multidrug Resistance of Antibiotics via Nanodelivery Systems.

Antibiotic resistance has become a threat to microbial therapies nowadays. The conventional approaches possess several limitations to combat microbial infections. Therefore, to overcome such complications, novel drug delivery systems have gained pharmaceutical scientists' interest. Significant findings have validated the effectiveness of novel drug delivery systems such as polymeric nanoparticles, liposomes, metallic nanoparticles, dendrimers, and lipid-based nanoparticles against severe microbial infections and combating antimicrobial resistance. This review article comprises the specific mechanism of antibiotic resistance development in bacteria. In addition, the manuscript incorporated the advanced nanotechnological approaches with their mechanisms, including interaction with the bacterial cell wall, inhibition of biofilm formations, activation of innate and adaptive host immune response, generation of reactive oxygen species, and induction of intracellular effect to fight against antibiotic resistance. A section of this article demonstrated the findings related to the development of delivery systems. Lastly, the role of microfluidics in fighting antimicrobial resistance has been discussed. Overall, this review article is an amalgamation of various strategies to study the role of novel approaches and their mechanism to fight against the resistance developed to the antimicrobial therapies.

Cannabis as a potential compound against various malignancies, legal aspects, advancement by exploiting nanotechnology and clinical trials.

Various preclinical and clinical studies exhibited the potential of cannabis against various diseases, including cancer and related pain. Subsequently, many efforts have been made to establish and develop cannabis-related products and make them available as prescription products. Moreover, FDA has already approved some cannabis-related products, and more advancement in this aspect is still going on. However, the approved product of cannabis is in oral dosage form, which exerts various limitations to achieve maximum therapeutic effects. A considerable translation is on a hike to improve bioavailability, and ultimately, the therapeutic efficacy of cannabis by the employment of nanotechnology. Besides the well-known psychotropic effects of cannabis upon the use at high doses, literature has also shown the importance of cannabis and its constituents in minimising the lethality of cancer in the preclinical models. This review discusses the history of cannabis, its legal aspect, safety profile, the mechanism by which cannabis combats with cancer, and the advancement of clinical therapy by exploiting nanotechnology. A brief discussion related to the role of cannabinoid in various cancers has also been incorporated. Lastly, the information regarding completed and ongoing trials have also been elaborated.

Formulation and development of tacrolimus-gellan gum nanoformulation for treatment of dry eye disease.

The present study aimed at the development and evaluation of tacrolimus gellan gum nanoparticles (TGNPs) for the effective management of dry eye disease (DED) following topical application. TGNPs were developed by ionotropic gelation between gellan gum and aluminum chloride. Developed TGNPs were nanosized (274.46 ± 8.90 nm) with high % encapsulation efficiency (74.2 ± 2.4%) and loading capacity (36.14 ± 1.7%). The nanosize and spherical morphology of TGNPs was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Fourier transform infrared spectroscopy (FTIR) revealed no interaction between drug and GG. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirms the conversion of crystalline tacrolimus to amorphous post encapsulation in the nanoparticle. TGNPs showed prolonged drug release throughout 12 h and higher pre-corneal retention compared to tacrolimus solution. HET-CAM studies, histopathological evaluation, and Draize test confirmed the safety of the formulation for ocular use. Further, the pharmacodynamic studies using experimental DED in rabbits showed that TGNPs are effective in treating symptoms of DED. In conclusion, topical delivery of TGNPs could hold potential for efficient management of DED.