Multifunctional nanotherapeutics for intracellular trafficking of doxorubicin against breast cancer.

Aims: To develop an estrone-targeted d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-based liposomal system for enhanced intracellular delivery of doxorubicin (DOX). Materials & methods: Zetasizer, transmission electron microscopy, energy dispersive x-ray, Fourier-transform infrared spectroscopy, differential scanning calorimetry, x-ray diffraction, confocal laser scanning microscopy and FACS analysis were used for formulation characterization and evaluation. Results: The DOX-LIPO-TPGS and DOX-LIPO-TPGS-estrone formulations had vesicle sizes (117.6 ± 3.51; 144 ± 5.00 nm), zeta potential (-36.4 ± 0.75; -35.8 ± 0.76), polydispersity index (0.123 ± 0.005; 0.169 ± 0.005) and percent entrapment efficiency (73.56 ± 3.55; 77.16 ± 3.83%) with improved cytotoxicity and cellular uptake, confirming the targeted potential of the developed formulations. Conclusion: The results suggest that the developed liposomal formulation with desired characteristics is potentially capable of nonimmunogenic, site-specific drug delivery to targeted cancer sites and reduced DOX-associated cardiac toxicity.

Doxorubicin (DOX) is an effective chemotherapy drug to treat breast cancer. However, DOX can cause unwanted side effects such as damage to the heart. This is due to side effects in healthy body tissues. This study was designed to develop nanoparticles that target cancer cells specifically to improve the delivery of DOX to these cells and prevent side effects elsewhere. Nanoparticles called liposomes were used as the platform for delivering DOX. Liposomes are sometimes coated with d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS), a synthetic vitamin D derivative. This helps the liposome evade the immune system and release the drug more effectively. TPGS was tethered with estrone (ES), a type of estrogen. Certain breast cancer cells have many more estrogen receptors on their cell surface than healthy cells. TPGS-ES was coated on DOX-loaded liposomes to achieve enhanced intracellular delivery of DOX to breast cancer cells specifically. These liposomes were called DOX-LIPO-TPGS-ES. This liposome proved more toxic to cells in a breast cancer cell line than free DOX or liposomes without tethered ES. When tested in rats, DOX-LIPO-TPGS-ES showed increased tumor uptake compared with free DOX or liposomes without tethered ES. Rats treated with either liposomal drug showed normal levels of key markers associated with heart function, whereas those treated with free DOX showed increased levels of these markers. These results suggest that DOX-LIPO-TPGS-ES is capable of highly targeted delivery of DOX with limited side effects.

Development and optimization of TPGS-based stealth liposome of doxorubicin using Box-Behnken design: characterization, hemocompatibility, and cytotoxicity evaluation in breast cancer cells.

The present work reports the development of doxorubicin (DOX) encapsulated α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated liposomal system (DOX-LIPO-TPGS) by quality by design (QbD) approach and evaluated for its anticancer and hemocompatibility potential. The screening and optimization of formulation variables were performed by the systematic design of experiments (DoE), using Taguchi and Box-Behnken design (BBD) for their desired quality attributes. The QbD optimized DOX-LIPO (DOX encapsulated uncoated liposome) and DOX-LIPO-TPGS formulation showed nano-metric vesicle size (98.2 ± 3.1 and 117.6 ± 3.5 nm) with favourable development parameters, i.e. PDI (0.262 ± 0.008 and 0.123 ± 0.005); ZP (-38.7 ± 0.5 and -36.4 ± 0.7 mV) and % EE (66.8 ± 3.3 and 73.5 ± 3.5%) respectively. The release kinetics parameters suggested, sustained release behaviour of developed liposomal formulations (83.6 ± 2.8 and 69.8 ± 2.2% releases in 72 h, respectively). Cytotoxicity (MTT assay) on the MCF-7 breast cancer cell line and haemolysis assay on RBCs stipulates comparatively higher anticancer potential and better hemocompatibility of DOX-LIPO-TPGS with respect to DOX-LIPO and the plain DOX solution. The study concluded that the QbD based three levels by three factors BBD optimization could be utilized for obtaining liposomal formulations with desired quality attributes. TPGS could be set out as a vital additive to improve the various quality parameters including stealthing character, stability, kinetic release, cytotoxicity, and hemocompatibility of liposomal formulations. This may serve as a focal paradigm for using TPGS-coated liposomes as anticancer drug delivery vehicle in normal and MDR carcinoma.

Nanotheranostics for Cancer Therapy and Detection: State of the Art.

Nanotheranostics, an approach of combining both diagnosis and therapy, is one of the latest advances in cancer therapy particularly. Nanocarriers designed and derived from inorganic materials such as like gold nanoparticles, silica nanoparticles, magnetic nanoparticles and carbon nanotubes have been explored for tremendous applications in this area. Similarly, nanoparticles composed of some organic material alone or in combination with inorganic nano-cargos have been developed pre-clinically and possess excellent features desired. Photothermal therapy, MRI, simultaneous imaging and delivery, and combination chemotherapy with a diagnosis are a few of the known methods exploring cancer therapy and detection at organ/tissue/molecular/sub-cellular level. This review comprises an overview of the recent reports meant for nano theranostics purposes. Targeted cancer nanotheranostics have been included for understating tumor micro-environment or cell-specific targeting approach employed. A brief account of various strategies is also included for the readers highlighting the mechanism of cancer therapy.

Dual cancer targeting using estrogen functionalized chitosan nanoparticles loaded with doxorubicin-estrone conjugate: A quality by design approach.

In this study, estrone was used as targeting functionality in chitosan nanoparticles (DoxEs-CSEsNPs) carrying doxorubicin-estrone conjugate for dual targeted intracellular delivery to breast cancer cells. Estrone was conjugated with Dox and CS and characterized by FTIR and FT-NMR spectroscopy. Dox/DoxEs containing CSEsNPs were prepared with ionic gelation method and for the effect of formulation variables a 3-factor, 3-level Box-Behnken design (BBD) was explored, which predict the responses like particle size (Y1) and percent entrapment efficiency (%EE) (Y2) when CSEs: TPP ratio (X1), sonication time (X2) and stirring speed (X3) were selected as independent variables. The Dox-CSEsNPs and DoxEs-CSEsNPs were characterized for size, shape, PDI, surface charge and thermal analysis. The drug entrapment efficiency was 66.33 ± 2.82% and 62.25 ± 2.63% for Dox-CSEsNPs and DoxEs-CSEsNPs formulation respectively. The in vitro release, haemolytic toxicity, and fluorescent microscopy studies were also assessed. Anticancer activity on the MCF-7 cell line indicated the higher potency of DoxEs-CSEsNPs as compared to Dox-CSEsNPs, DoxEs, and Dox solution. The findings are decisive for selective targeting of antineoplastic agents to the ERs, which indicate that the DoxEs loaded CSEsNPs were able to significantly improve the efficacy of Dox.

Galactosylated TPGS Micelles for Docetaxel Targeting to Hepatic Carcinoma: Development, Characterization, and Biodistribution Study.

Hepatocellular carcinoma (HCC) is a foremost type of cancer problem in which asialoglycoprotein receptors are overexpressed. In this study, asialoglycoprotein receptor-targeted nanoformulation (galactose-conjugated TPGS micelles) loaded with docetaxel (DTX) was developed to achieve its site-specific delivery for HCC therapy. The pharmaceutical characteristics like shape morphology, average particle size and zeta potential, drug entrapment efficiency, and in vitro release kinetics of developed system were evaluated. DTX-loaded galactosylated TPGS (DTX-TPGS-Gal) micelles and TPGS micelles (DTX-TPGS) were having 58.76 ± 1.82% and 54.76 ± 1.42% entrapment of the DTX, respectively. In vitro drug release behavior from micelles was controlled release. Cytotoxicitiy (IC50) of DTX-TPGS-Gal formulation on HepG2 cell lines was significantly (p ≤ 0.01) lower (6.3 ± 0.86 µg/ml) than DTX-TPGS (9.06 ± 0.82 µg/ml) and plain DTX (16.06 ± 0.98 µg/ml) indicating higher efficacy of targeted formulation. Further, in vivo biodistribution studies in animal model showed maximum drug accumulation at target site, i.e., the liver in the case of DTX-TPGS-Gal as compared with non-targeted one. It is concluded from the findings that TPGS-Gal micelles can be utilized for targeted drug delivery of cytotoxic drugs towards HCC with minimized side effects. Graphical abstract.

Solid lipid nanoparticles: a review on recent perspectives and patents.

Introduction: Solid lipid nanoparticles (SLNs) are solid core lipid nanocarriers, which can hold both hydrophilic and hydrophobic drugs. They can be made up of biocompatible ingredients and therefore are one of the preferred choices for drug delivery. Surface modifications of SLNs may further provide unique features to them like mucoadhesiveness or targeting capability.Areas covered: In this review, the authors have covered areas from the basic introduction of SLNs to its applications in controlled drug delivery. More specifically, the authors have covered patents disclosed related to the SLNs for the period 2014-2019; however, a summary of patents of 2008-2013 is also included.Expert opinion: SLNs have been explored for development of compositions/formulations with improved therapeutics or cosmetic applications or for nutraceutical applications. Targeted SLNs compositions have been patented as evidenced from the literature; however, not such types of enough SLNs formulations have been claimed for the same.

Transdermal Drug Delivery: Opportunities and Challenges for Controlled Delivery of Therapeutic Agents Using Nanocarriers.

BACKGROUND: Transdermal drug delivery represents an extremely attractive and innovative route across the skin owing to the possibility for achieving systemic effect of drugs. The present scenario demands a special focus on developing safe medicine with minimized toxic adverse effects related to most of the pharmacologically active agents. Transdermal drug delivery would be a focal paradigm which provides patient convenience, first-pass hepatic metabolism avoidance, local targeting and reduction in toxic effect related to various categories of drugs like, analgesics, antiinflammatory, antibiotics, antiviral, anaesthetic, anticancer etc. Even this route has challenges due to highly organized structure of skin which acts as a main barrier to penetration of drug via the skin. METHOD: Several alternative possible strategies are available which overcome these barriers, including use of penetration enhancer, eletroporation, iontophoresis and various nanotechnologically developed nanocarrier systems. The latest one includes employing liposome, dendrimers, nanoparticles, ethosome, carbon nanotube and many more to avoid associated limitations of conventional formulations. Numerous transdermal products such as Estrasorb, Diractin, VivaGel®, Daytrana®, Aczone, Sileryst® are available in the market having a novel strategy to achieve higher penetration of drugs. This encourages formulation fraternity to develop structurally deformable and stable nanocarriers as an alternative approach for controlled and reliable drug delivery across the skin barrier. DISCUSSION: In this review, we will discuss nanocarriers mediated approaches that come-up with the solutions to the different challenges towards transdermal drug delivery, its clinical importance and latest insight to research in it. CONCLUSION: The reports presented in this review confirm the wide application of nanocarriers for transdermal delivery of drug/gene.

Nanomedicine to Deal With Cancer Cell Biology in Multi-Drug Resistance.

Today Cancer still remains a major cause of mortality and death worldwide, in humans. Chemotherapy, a key treatment strategy in cancer, has significant hurdles such as the occurrence of chemoresistance in cancer, which is inherent unresponsiveness or acquired upon exposure to chemotherapeutics. The resistance of cancer cells to an antineoplastic agent accompanied to other chemotherapeutic drugs with different structures and mechanisms of action called multi-drug resistance (MDR) plays an important role in the failure of chemo- therapeutics. MDR is primarily based on the overexpression of drug efflux pumps in the cellular membrane, which belongs to the ATP-binding cassette (ABC) superfamily of proteins, are P-gp (P-glycoprotein) and multidrug resistance-associated protein (MRP). Over the years, various strategies have been evaluated to overcome MDR, based not only on the use of MDR modulators but also on the implementation an innovative approach and advanced nanosized drug delivery systems. Nanomedicine is an emerging tool of chemotherapy that focuses on alternative drug delivery for improvement of the treatment efficacy and reducing side effects to normal tissues. This review aims to focus on the details biology, reversal strategies option with the limitation of MDR and various advantages of the present medical science nanotechnology with intracellular delivery aspects for overcoming the significant potential for improving the treatment of MDR malignancies.

Hyaluronic acid modified pH-sensitive liposomes for targeted intracellular delivery of doxorubicin.

CONTEXT: Surface-modified pH-sensitive liposomal system may be useful for intracellular delivery of chemotherapeutics. OBJECTIVE: Achieving site-specific targeting with over-expressed hyaluronic acid (HA) receptors along with using pH sensitive liposome carrier for intracellular drug delivery was the aim of this study. MATERIALS AND METHODS: Stealth HA-targeted pH-sensitive liposomes (SL-pH-HA) were developed and evaluated to achieve effective intracellular delivery of doxorubicin (DOX) vis-a-vis enhanced antitumor activity. RESULTS: The in vitro release studies demonstrated that the release of DOX from SL-pH-HA was pH-dependent, i.e. faster at mildly acidic pH ∼5, compared to physiological pH ∼7.4. SLpH-HA was evaluated for their cytotoxicity potential on CD44 receptor expressing MCF-7 cells. The half maximal inhibitory concentration (IC50) of SL-pH-HA and SL-HA were about 1.9 and 2.5 µM, respectively, after 48 h of incubation. The quantitative uptake study revealed higher localization of targeted liposomes in the receptor positive cells, which was further confirmed by fluorescent microscopy. The antitumor efficacy of the DOX-loaded HA-targeted pH-sensitive liposomes was also verified in a tumor xenograft mouse model. DISCUSSION: DOX was efficiently delivered to the tumor site by active targeting via HA and CD44 receptor interaction. The major side-effect of conventional DOX formulation, i.e. cardiotoxicity was also estimated by measuring serum enzyme levels of LDH and CPK and found to be minimized with developed formulation. Overall, HA targeted pH-sensitive liposomes were significantly more potent than the non-targeted liposomes in cells expressing high levels of CD44. CONCLUSION: Results strongly implies the promise of such liposomal system as an intracellular drug delivery carrier developed for potential anticancer treatment.

Nanocarriers in Improved Heparin Delivery: Recent Updates.

Heparin, a well known drug for anticoagulant therapy and prophylaxis of deep vein thrombosis and coronary syndromes, is also involved in numerous pathological processes such as inflammation, immune cell migration, tumor cell metastasis, smooth muscle cell proliferation etc. Though heparin is a clinically used anticoagulant with minimal side effects and drug interactions, its clinical use is limited due to parenteral administration. Alternatively, noninvasive delivery approaches such as oral, nasal, pulmonary or transdermal route are being explored that may deal with problems associated with parenteral heparin without compromising therapeutic benefits. For the successful noninvasive delivery of such a large drug candidate, the biological and biochemical barriers must be overcome to achieve a clinically acceptable therapeutic advantage. Nanocarriers significantly improve the pharmacokinetics and clinical effectiveness of the loaded therapeutics by either protecting them from unfavorable bioenvironment or modifying their release at the target site. Novel carriers such as liposomes, nanoparticles, dendrimers etc. have been developed to improve the bioavailability of heparin through various routes of delivery. Overall, the present review provides complete insight to the research that has been carried out for heparin delivery through various routes.

A review of mechanistic insight and application of pH-sensitive liposomes in drug delivery.

The pH-sensitive liposomes have been extensively used as an alternative to conventional liposomes in effective intracellular delivery of therapeutics/antigen/DNA/diagnostics to various compartments of the target cell. Such liposomes are destabilized under acidic conditions of the endocytotic pathway as they usually contain pH-sensitive lipid components. Therefore, the encapsulated content is delivered into the intracellular bio-environment through destabilization or its fusion with the endosomal membrane. The therapeutic efficacy of pH-sensitive liposomes enables them as biomaterial with commercial utility especially in cancer treatment. In addition, targeting ligands including antibodies can be anchored on the surface of pH-sensitive liposomes to target specific cell surface receptors/antigen present on tumor cells. These vesicles have also been widely explored for antigen delivery and serve as immunological adjuvant to enhance the immune response to antigens. The present review deals with recent research updates on application of pH-sensitive liposomes in chemotherapy/diagnostics/antigen/gene delivery etc.

Targeted breast cancer nanotherapeutics: options and opportunities with estrogen receptors.

Breast cancer is a multifarious and heterogeneous disease. Identification of molecular alterations of surface/intracellular proteins particularly involved in proliferation and growth of breast cancer cells provides opportunities for the development of new targets for therapy. Several ligands that are routinely employed in targeted delivery to breast cancer cells have been found to be immunogenic. Therefore, endogenous bioligands may serve as a better option, which may be bio-competent and non-immunogenic, including estrogens. Membrane-associated estrogen binding sites are highly over-expressed in cancers of endocrine origin, such as breast. The selective high density of these receptor portals can be utilized for targeted breast cancer therapy. Numerous estrogen-chemotherapeutic agent conjugates have been successfully utilized for targeted drug/DNA delivery. Recently, nanocarrier(s) anchored with estrogens as site-directing ligands for the delivery of bioactive(s) have been exhaustively investigated for breast cancer therapy. This review presents a detail account of how estrogens, anti-estrogens, and their derivatives can be used for site-specific delivery of bioactive(s) to breast cancer cells. The sequential emergence of various estrogen-anticancer drug conjugates is highlighted. Additionally, carrier systems that utilize estrogens/anti-estrogens as ligands for purpose-specific site-selective novel drug delivery platforms have been reviewed and revisited in terms of their realistic clinical applications in breast cancer treatment.

Liposomal nanomedicine for breast cancer therapy.

Liposomes are well-established nanocarriers for improving the therapeutic index of anticancer agents. A remarkable understanding in the pathophysiology of breast cancer progression has emerged with information on the involved specific biomolecules, which may serve as molecular targets for its therapy. Hormonal and nonhormonal receptors can both be exploited for targeting to breast cancer cells. Targeted delivery of cytotoxic drugs using liposomes is a novel approach for breast cancer therapy. In the present article, we summarize molecular targets present on the breast cancer cells. Recent developments in liposome-based delivery of bioactives for selective treatments of breast cancer are discussed. In addition, utilization of bioenvironmental conditions of tumor for liposome-based targeted delivery is also summed up.

A novel cancer targeting approach based on estrone anchored stealth liposome for site-specific breast cancer therapy.

We here report the successful utilization of estrogen receptor (ER) for the delivery of anticancer drug doxorubicin (DOX) encapsulated within pegylated liposome for the treatment of breast cancer. Estrone (ES) was anchored as ligand on to stealth liposome (ES-SL-DOX) for targeting to ERs. In vitro cytotoxicity study was conducted on ER positive and negative breast carcinoma cells. The fluorescent microscopy studies were performed with estrone anchored stealth liposome (ES-SL) loaded with 6-carboxyfluorescein (6-CF). Pharmacokinetic, tissue distribution studies and tumor growth inhibition were carried out followed by intravenous (i.v.) administration of liposomal formulations. ES-SL-DOX demonstrated strongest cytotoxicity to the ER positive cell lines as compared to non-targeted formulations i.e. SL-DOX and plain DOX confirming that ES-SL-DOX was effectively taken up by cells expressing ERs. The half-life (t(1/2)) of SL-DOX and ES-SL-DOX was about 9 and 13 fold higher than that of the free DOX, respectively. Accumulation of ES-SL-DOX in the tumor tissue was 24.27 and 6.04 times higher as compared to free DOX and SL-DOX respectively, after 8 h. ES-SL-DOX at a dose of 5 mg DOX/kg resulted in effective retardation of tumor growth. These findings support that estrogen receptor(s) may be utilized as potential target for chemotherapy of cancers and estrone anchored stealth liposomes could be one of the promising solutions for the delivery of anticancer agent to breast tumors with reduced side-effects.

Development and characterization of effective topical liposomal system for localized treatment of cutaneous candidiasis.

The localized delivery of fluconazole (FLZ) by conventional therapy is a major impediment in achieving its therapeutic efficacy against skin infections, such as cutaneous candidiasis. Therefore, the present study was aimed to develop FLZ-loaded vesicular construct(s), such as liposomes and niosomes, incorporated into carbopol gel (1%; w/w) for sustained, localized application. The liposomes and niosomes were prepared by the lipid/nonionic surfactant-based dry-film hydration method and were characterized for different parameters. In addition, antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed albino rats. The results showed that the size of liposomes and niosomes was found to be 0.348 ± 0.054 and 0.326 ± 0.033 µm with encapsulation efficiency of 31.8 ± 1.36 and 27.6 ± 1.08%, respectively. The skin-retention studies of FLZ from in vitro and in vivo experiments showed significantly higher accumulation of drug in the case of liposomal gel. The in vivo localization studies in viable skin showed that liposomal gel could produce 14.2-fold higher drug accumulation, compared with plain gel, while it was 3.3-fold more in the case of an equivalent-dose application in the form of niosomal gel. The antifungal study also confirmed the maximum therapeutic efficacy of liposomal gel, as the lowest number of cfu/mL was recorded following liposomal FLZ application. The studies signify the potential of liposomal gel for topical delivery of FLZ with increased accumulation of drug in various strata of skin vis-a-vis through sustained release of drug could maintain the localized effect, resulting in an effective treatment of a life-threatening cutaneous fungal infection.

Nanocarriers in ocular drug delivery: an update review.

Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drug-contact time and poor ocular bioavailability due to drainage of solution, tear turnover and its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery systems. Nanosized carriers like micro/nano-suspensions, liposome, niosome, dendrimer, nanoparticles, ocular inserts, implants, hydrogels and prodrug approaches have been developed for this purpose. These novel systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. Conventional delivery systems get diluted with tear, washed away through the lacrimal gland and usually require administering at regular time intervals whereas nanocarriers release drug at constant rate for a prolonged period of time and thus enhance its absorption and site specific delivery. This review presents an overview of the various aspects of the ocular drug delivery, with special emphasis on nanocarrier based strategies, including structure of eye, its barriers, delivery routes and the challenges/limitations associated with development of novel nanocarriers. The recent progresses in therapy of ocular disease like gene therapy have also been included so that future options should also be considered from the delivery point of view. Recent progress in the delivery of proteins and peptides via ocular route has also been incorporated for reader benefit.

Engineered chylomicron mimicking carrier emulsome for lymph targeted oral delivery of methotrexate.

The aim of the present study was to develop chylomicron mimicking carrier emulsome for oral lymphatic delivery of methotrexate (MTX), an anticancer drug. The compritol 888 ATO (CA) was used as lipid core and soya lecithin (PC) as stabilizer. The optimized emulsome (1:1.2 mole ratio of CA:PC) showed mean particle size of 160.3+/-10.2 nm and with 72.8+/-6.5% drug entrapment efficiency. The differential scanning calorimetric studies revealed a depression in endothermic onset for MTX loaded emulsome. The rapid burst release of the drug was observed in simulated gastric fluid (SGF pH 1.2) with significant increase in particle size of emulsome. However in simulated intestinal fluid (SIF, pH 7.4) a slow and consistent release of the drug was obtained over period of 24 h. Storage stability studies were performed at different temperatures (4+/-1 and 25+/-1 degrees C) for 3 months which suggested that EML remain more stable when stored at refrigerated condition. The in vivo studies were carried out on albino rats and response was estimated collecting blood and lymph both. The pharmacokinetic parameters C(max), t(max) and AUC(0-->12h) after duodenal administration of optimized emulsomal formulation and plain MTX solution were 7.1 and 2.4 microg/mL, 4 and 1 h, 40.45 and 7.2 h microg/mL respectively. The relative bioavailability of MTX was enhanced nearly 5.7 times with optimized EML formulation when compared to plain MTX solution with higher uptake and longer residence time of MTX molecules in lymphatics. Thus, emulsome could be used as lymphotropic carrier for delivery of bioactive(s) and hence for bioavailability enhancement.

Chitosan and its role in ocular therapeutics.

From the past few decades, tremendous awareness has been laid on the use of natural polymers in ocular drug delivery. Chitosan, a modified natural carbohydrate polymer, has number of applications in the field of ophthalmics and attracted a great deal of attention of scientific community, academicians and environmentalists due to its unique features. Chitosan has been explored for the delivery of drugs, genes, biotechnological products, proteins and peptides to the target site within ocular tissues. Chitosan being a polycationic in nature interacts with the polyanionic surface of ocular mucosa through hydrogen bonding /ionic interactions and enhance the mucoadhesive effect of formulation. Sustained and controlled ocular delivery can be achieved with chitosan based formulations like chitosan gels, inserts, chitosan coated liposome/niosome and chitosan nanoparticles. This review discussed various aspects related to chitosan and chitosan based formulations particularly developed for ocular therapeutics. The fate and toxicological consideration related to chitosan, resulting with its interaction to ocular tissues, has also been summed up in addition.