From Vision Correction to Drug Delivery: Unraveling the Potential of Therapeutic Contact Lens.

Contact lenses (CLs) have become an essential tool in ocular drug delivery, providing effective treatment options for specific eye conditions. In recent advancements, Therapeutic CLs (TCLs) have emerged as a promising approach for maintaining therapeutic drug concentrations on the eye surface. TCLs offer unique attributes, including prolonged wear and a remarkable ability to enhance the bioavailability of loaded medications by more than 50%, thus gaining widespread usage. They have proven beneficial in pain management, medication administration, corneal healing, and protection. To achieve sustained drug delivery from TCLs, researchers are exploring diverse systems, such as polymeric nanoparticulate systems, lipidic systems, and the incorporation of agents like vitamin E or rate-limiting polymers. However, despite breakthrough successes, certain challenges persist, including ensuring drug stability during processing and manufacturing, controlling release kinetics, and biomaterial interaction, reducing protein adhesion, and addressing drug release during packaging and storage etc. While TCLs have shown overall success in treating corneal and ocular surface disorders, careful consideration of potential issues and contraindications is vital. This review offers an insightful perspective on the critical aspects that need to be addressed regarding TCLs, with a specific emphasis on their advantages and limitations.

Unlocking the power of sugar: carbohydrate ligands as key players in nanotherapeutic-assisted targeted cancer therapy.

Cancer cells need as much as 40-times more sugar than their normal cell counterparts. This sugar demand is attained by the excessive expression of inimitable transporters on the surface of cancer cells, driven by their voracious appetite for carbohydrates. Nanotechnological advances drive research utilizing ligand-directed therapeutics and diverse carbohydrate analogs. The precise delivery of these therapeutic cargos not only mitigates toxicity associated with chemotherapy but also reduces the grim toll of mortality and morbidity among patients. This in-depth review explores the potential of these ligands in advanced cancer treatment using nanoparticles. It offers a broader perspective beyond the usual ways we deliver drugs, potentially changing the way we fight cancer.

From Traditional Medicine to Advanced Therapeutics: The Renaissance of Phyto-nano Interventions in Psoriasis.

Psoriasis is an autoimmune systemic chronic inflammatory disease that exhibits characteristic detrimental effects on the skin, often leading to infections or comorbid conditions. The multifaceted nature of psoriasis has made it very challenging to treat, especially with current chemotherapy options. Therefore, it is essential to consider phytoconstituents as novel alternatives. However, despite demonstrating higher anti-inflammatory, anti-psoriasis, and immunomodulatory potential, their clinical usage is hindered due to their poor physicochemical properties. To address these drawbacks, nanoparticulate drug delivery systems have been developed, helping to achieve better permeation of phytoconstituents through topical administration. This has breathed new life into traditional systems of medicine, particularly in the context of treating psoriasis. In this current review, we present a detailed, comprehensive, and up-to-date analysis of the literature, which will contribute to affirming the clinical role of phyto-nano interventions against psoriasis.

The Prospects of Phytomedicines and Nanomedicines to Treat Leishmaniasis: A Comprehensive Review.

The global shift in lifestyle has prompted health agencies to redirect their focus from poverty-related diseases to the emergence of lifestyle diseases prevalent in privileged regions. As a result, these diseases have been labeled as "neglected diseases," receiving limited research attention, funding, and resources. Neglected Tropical Diseases (NTDs) encompass a diverse group of vector-borne protozoal diseases that are prevalent in tropical areas worldwide. Among these NTDs is leishmaniasis, a disease that affects populations globally and manifests as skin abnormalities, internal organ involvement, and mucous-related abnormalities. Due to the lack of effective and safe medicines and vaccines, it is crucial to explore alternative resources. Phytomedicine, which comprises therapeutic herbal constituents with anti-leishmanial properties, holds promise but is limited by its poor physicochemical properties. The emerging field of nanomedicine has shown remarkable potential in revitalizing the anti-leishmanial efficacy of these phytoconstituents. In this investigation, we aim to highlight and discuss key plant constituents in combination with nanotechnology that have been explored in the fight against leishmaniasis.

Small molecules as cancer targeting ligands: Shifting the paradigm.

Conventional chemotherapeutics exploration is hampered due to their nonspecific distribution leading to unintended serious toxicity. Toxicity is so severe that deciding to go for chemotherapy becomes a question of concern for many terminally ill cancer patients. However, with evolving times nanotechnology assisted in reducing the haywire distribution and channelizing the movement of drug-enclosing drug delivery systems to cancer cells to a greater extent, yet toxicity issues still could not be obliterated. Thus, active targeting appeared as a refuge, where ligands actively or specifically deliver linked chemotherapeutics and carriers to cancer cells. For a very long time, large molecule weight/macromolecular ligands (peptides and big polymers) were considered the first choice for ligand-directed active cancer targeting, due to their specificity towards overexpressed native cancer receptors. However, complex characterization, instability, and the expensive nature demanded to reconnoitre better alternatives for macromolecule ligands. The concept of small molecules as ligands emerged from the idea that few chemical molecules including chemotherapeutics have a higher affinity for cancer receptors, which are overexpressed on cell membranes, and may have the ability to assist in drug cellular uptake through endocytosis. But now the question is, can they assist the conjugated macro cargos to enter the cell or not? This present review will provide a holistic overview of the small molecule ligands explored till now.

Nanomaterials in Dentistry: Current Applications and Future Scope.

Nanotechnology utilizes the mechanics to control the size and morphology of the particles in the required nano range for accomplishing the intended purposes. There was a time when it was predominantly applied only to the fields of matter physics or chemical engineering, but with time, biological scientists recognized its vast benefits and explored the advantages in their respective fields. This extension of nanotechnology in the field of dentistry is termed 'Nanodentistry.' It is revolutionizing every aspect of dentistry. It consists of therapeutic and diagnostic tools and supportive aids to maintain oral hygiene with the help of nanomaterials. Research in nanodentistry is evolving holistically but slowly with the advanced finding of symbiotic use of novel polymers, natural polymers, metals, minerals, and drugs. These materials, in association with nanotechnology, further assist in exploring the usage of nano dental adducts in prosthodontic, regeneration, orthodontic, etc. Moreover, drug release cargo abilities of the nano dental adduct provide an extra edge to dentistry over their conventional counterparts. Nano dentistry has expanded to every single branch of dentistry. In the present review, we will present a holistic view of the recent advances in the field of nanodentistry. The later part of the review compiled the ethical and regulatory challenges in the commercialization of the nanodentistry. This review tracks the advancement in nano dentistry in different but important domains of dentistry.

Green surfactant-dendrimer aggreplexes: An ingenious way to launch dual attack on arch-enemy cancer.

Combination therapy, which combines anti-cancer drugs with different oligonucleotides, have shown potential in cancer treatment. However, delivering a hydrophobic anti-cancer drug and a hydrophilic oligonucleotide simultaneously is a herculean task. This study takes advantage of interactions between histidine-lauric acid-based green surfactant and poly(amidoamine) dendrimers to achieve this aim. The green surfactant was synthesized by carbodiimide chemistry and characterized by FTIR, 1H-NMR, and mass spectroscopy. Further, green surfactant-dendrimer aggregates encapsulating DTX and complexing SIRT 1 shRNA i.e., "aggreplexes" were developed and characterized. The term "aggreplexes" signifies complexes which are formed between green-surfactant-dendrimer aggregates and SIRT-1 shRNA via electrostatic interaction. The aggreplexes displayed particle size of 262.33 ± 3.87 nm, PDI of 0.25 and entrapment efficiency of 70.56 %. The TEM images revealed spherical shape of aggreplexes with irregular outer surface and corroborated particle size obtained from zetasizer. The in-vitro release study revealed biphasic release patterns of DTX from aggreplexes and were compatible for intravenous administration. Further, aggreplexes augmented cellular uptake in MDA-MB-231 cells by ∼1.87-fold compared to free DTX. Also, EGFP expression revealed significantly higher transfection of aggreplexes compared to naked shRNA and Superfect™ complexes. Further, aggreplexes showed higher cytotoxicity in MDA-MB-231 cells and ∼4.16-fold reduction in IC50 value compared to free DTX. Finally, apoptosis-index observed in case of aggreplexes was ∼3.57-fold higher than free DTX. These novel aggreplexes showed increased drug loading capacity and superior gene transfection potential. Thus, they open new avenues for co-delivery of hydrophobic anti-cancer drugs and hydrophilic therapeutic genes for improving current standards of cancer therapy.

QbD-steered development of mixed nanomicelles of galantamine: Demonstration of enhanced brain uptake, prolonged systemic retention and improved biopharmaceutical attributes.

PURPOSE: Numerous oral treatment options have been reported for neurological disorders, especially Alzheimer's disease (AD). Galantamine (GAL) is one of such drugs duly approved for management of AD. However, it exhibits poor brain penetration, low intestinal permeation and requires frequent dosing in AD treatment. The present studies, accordingly, were undertaken to develop DSPE-PEG 2000-based micelles loaded with GAL for efficient brain uptake, improved and extended pharmacokinetics, along with reduced dosing regimen. METHODS: Mixed nanomicelles (MNMs) were systematically formulated using QbD approach, and characterized for morphology, entrapment efficiency andin vitrodrug release. RESULTS: Studies on CaCo-2 and neuronal U-87 cell lines exhibited substantial enhancement in the cellular permeability and uptake of the developed MNMs. Pharmacokinetic studies performed on rats showed significantly improved values of plasma AUC (i.e., 2.28-fold, p < 0.001), ostensibly due to bypassing of hepatic first-pass metabolism and improved intestinal permeability, together with significant rise in MRT (2.08-fold, p < 0.001) and tmax (4.80-fold; p < 0.001) values, indicating immense potential for prolonged drug residence in body.Besides, substantial elevation in brain drug levels, distinctly improved levels of biochemical parameters in brain homogenates and cognitive improvement in ß-amyloid-treated rats, testify the superiority in MNMs in therapeutic management of AD. CONCLUSIONS: The preclinical findings of the developed nanocarrier systems successfully demonstrate the notable potential of enhanced drug efficacy, extended duration of action and improved patient compliance.

pH sensitive liposomes assisted specific and improved breast cancer therapy using co-delivery of SIRT1 shRNA and Docetaxel.

Combining the bio-therapeutics with chemotherapeutic drugs can assist in augmenting the therapeutic standards by increasing the efficacy and decreasing the toxicity. Hence, in the present investigation Docetaxel (DTX) loaded pH-sensitive SIRT1 shRNA complexed lipoplex (DTX-lipoplex) were developed and explored for their improved breast cancer potential. The DTX-lipoplex were prepared by solvent evaporation and rehydration method and were evaluated for various quality attributes (particle size, % entrapment efficiency, hemotoxicity, DNA stability efficiency etc.), in vitro drug release, cell culture assays, antitumor efficacy and in vivo toxicity. The DTX-lipoplex exhibited a size of ~200 nm and zeta-potential of ~20 mV with ~70% encapsulation. Through systematic in vitro and in vivo examinations, DTX-lipoplex showed ~3 fold higher DTX titre within the tumor cells thereby significantly reducing the tumor burden (~78%) when compared to the marketed non pH sensitive lipid transfection agent and clinical counterpart i.e. Taxotere®. Thus, to conclude it can be said that co-delivering DTX and SIRT1 shRNA in a single tumor-specific nano-platform can improve the therapeutic potential of current therapy.

Nebulised surface-active hybrid nanoparticles of voriconazole for pulmonary Aspergillosis demonstrate clathrin-mediated cellular uptake, improved antifungal efficacy and lung retention.

BACKGROUND: Incidence of pulmonary aspergillosis is rising worldwide, owing to an increased population of immunocompromised patients. Notable potential of the pulmonary route has been witnessed in antifungal delivery due to distinct advantages of direct lung targeting and first-pass evasion. The current research reports biomimetic surface-active lipid-polymer hybrid (LPH) nanoparticles (NPs) of voriconazole, employing lung-specific lipid, i.e., dipalmitoylphosphatidylcholine and natural biodegradable polymer, i.e., chitosan, to augment its pulmonary deposition and retention, following nebulization. RESULTS: The developed nanosystem exhibited a particle size in the range of 228-255 nm and drug entrapment of 45-54.8%. Nebulized microdroplet characterization of NPs dispersion revealed a mean diameter of ≤ 5 µm, corroborating its deep lung deposition potential as determined by next-generation impactor studies. Biophysical interaction of LPH NPs with lipid-monolayers indicated their surface-active potential and ease of intercalation into the pulmonary surfactant membrane at the air-lung interface. Cellular viability and uptake studies demonstrated their cytocompatibility and time-and concentration-dependent uptake in lung-epithelial A549 and Calu-3 cells with clathrin-mediated internalization. Transepithelial electrical resistance experiments established their ability to penetrate tight airway Calu-3 monolayers. Antifungal studies on laboratory strains and clinical isolates depicted their superior efficacy against Aspergillus species. Pharmacokinetic studies revealed nearly 5-, 4- and threefolds enhancement in lung AUC, Tmax, and MRT values, construing significant drug access and retention in lungs. CONCLUSIONS: Nebulized LPH NPs were observed as a promising solution to provide effective and safe therapy for the management of pulmonary aspergillosis infection with improved patient compliance and avoidance of systemic side-effects.

Exploring the potential of novel pH sensitive lipoplexes for tumor targeted gene delivery with reduced toxicity.

The present investigation explores the potential of pH sensitive cationic liposomes for its in vivo tumor targeted gene transfection in comparison to its marketed transfecting reagent Lipofectamine® 2000. The lipoplexes were prepared by varying the molar mass ratio of cationic pH-sensitive liposomes with respect to pDNA and were evaluated for optimum size, zeta potential and for complete gel retardation. Similarly, the stability of lipoplexes in the presence of DNase I and serum was evaluated by using gel retardation and heparin displacement assay. The in vitro hemocompatibility assessment of pDNA lipoplexes revealed < 8.5% of hemolysis which was lower than the hemolysis observed for Lipofectamine® lipoplexes (15.9%). The internalization and pH dependent uptake inhibition using ammonium chloride in MCF-7 cells revealed higher internalization and pH sensitive nature of the prepared pH-sensitive system. The pDNA lipoplexes displayed > 80% of cell viability along with 4.42, 5.18 and 5.00 fold higher transfection efficiency than Lipofectamine® lipoplexes in MCF-7, HeLa and HEK-293 cells respectively. Also the in vivo toxicity assessment exhibited no significant change in the levels of biomarkers and no histopathological deformations in case of pDNA lipoplexes treated animals in comparison to control group (PBS). Further, pDNA lipoplexes demonstrated ~1.3 fold higher tumor transfection over Lipofectamine® lipoplexes indicating superior in vivo gene deliverable capabilities. Thus, the developed pH sensitive lipoplexes promises to be a potential tumor targeting and safe delivery system than Lipofectamine® 2000.

Mechanistic insights into high permeation vesicle-mediated synergistic enhancement of transdermal drug permeation.

Aim: To design a nanocarrier platform for enhanced transdermal drug permeation. Materials & methods: Gel-based high permeation vesicles (HPVs) were developed and their performance in terms of transdermal flux improvement, in vitro release and skin irritancy was assessed. The mechanistic insights of permeation enhancement were explored using confocal laser scanning microscopy, ATR-FTIR, DSC and P31 NMR. Results: HPVs exhibited as vesicles with uniform size (∼150 nm), extended drug-release profile (∼48 h) and improved transdermal flux. HPVs were also nontoxic and nonirritant to skin. Enhanced vesicle deformability, improved vesicle membrane fluidity and synergistic permeation enhancement action of synergistic combination of permeation enhancer components was found to be responsible for HPV-mediated permeation enhancement. Conclusion: Overall, the study established that HPVs demonstrate a promising therapeutic advantage over conventional transdermal drug carriers.

Chemosensitizer and docetaxel-loaded albumin nanoparticle: overcoming drug resistance and improving therapeutic efficacy.

AIM: Investigated strategy exploits the utilization of quercetin as a chemosensitizer for docetaxel (DTX), which was incorporated into albumin nanoparticles (NPs; bovine serum albumin NPs [BSA-NPs]). MATERIAL & METHODS: BSA-NPs containing both drugs were optimized, extensively characterized for different quality attributes and performance was investigated using series of in vitro and in vivo investigations. RESULTS: Co-encapsulated BSA-NPs exhibited size: 209.26 ± 9.84 nm, polydispersibility index: 0.184 ± 0.05 and good entrapment efficiency (∼75% for DTX and ∼68% for quercetin). Higher in vitro cytotoxicity, cell uptake and apoptosis were achieved in MCF-7 cell line. Similarly, higher P-glycoprotein efflux inhibition was observed in MDA-MB-231. About 2.5-fold increase in bioavailability of DTX was achieved with improved antitumor efficacy and reduced in vivo toxicity. CONCLUSION: Developed BSA-NPs provide an effective and safer alternative approach using co-delivery of chemosensitizer.

Amphotericin B Loaded Chitosan Nanoparticles: Implication of Bile Salt Stabilization on Gastrointestinal Stability, Permeability and Oral Bioavailability.

Through current investigation, we presented a lucrative way to formulate amphotericin B loaded bile salt stabilized carbohydrate polymer i.e. chitosan nanoparticles (NPs) for enhancing gastrointestinal stability of NPs thereby increasing the oral bioavailability of the drug. NPs were prepared using ionic gelation method, and stabilized using bile salt to provide gastric pH stability to chitosan NPs. NPs were optimized on different parameters such as particle size, encapsulation efficiency and estimated for their in vitro and in vivo performance. Developed NPs presented a higher stability in gastrointestinal milieu, reduced haemolytic toxicity and significantly higher uptake in Caco-2 cell lines followed by increased bioavailability as compared to naive drug, marketed formulation i.e. Fungizone® and uncoated chitosan NPs. Biochemical parameters and histology further substantiated the lower toxicity. In nutshell, the present research explored the bioadhesive and higher uptake potential of cationic carbohydrate polymer at the same time along with bile salts for stabilization of NPs in gastric milieu.

Codelivery of benzoyl peroxide & adapalene using modified liposomal gel for improved acne therapy.

AIM: Current study investigates therapeutic efficacy and tolerability of benzoyl peroxide (BPO)- and adapalene (AD)-loaded modified liposomal gel (BPO-AD-mLipo gel) for improved acne therapy. MATERIALS & METHOD: BPO-AD-mLipo were optimized and loaded in Carbopol gel. Both BPO-AD-mLipo and BPO-AD-mLipo-gel were extensively characterized for different quality attributes. Ex vivo dermal bioavailability, dermal distribution, in vivo anti-acne efficacy and skin irritation studies were performed and compared with marketed formulation (Epiduo®, Galderma Laboratories LP, TX, USA). RESULTS: BPO-AD-mLipo illustrated size 256.4 ± 9.3 nm with polydispersity index âˆ¼ 0.2. Significantly enhanced dermal bioavailability (AD-2.1, 5.4; BPO-3.0, 7.83-fold) and reduction in skin irritation and papule density in animal model were observed with BPO-AD-mLipo-gel as compared with free drugs and Epiduo, respectively. CONCLUSION: BPO-AD-mLipo gel provides effective and safer alternative approach for codelivery of anti-acne drugs.

Lyotropic Liquid Crystalline Nanoparticles of Amphotericin B: Implication of Phytantriol and Glyceryl Monooleate on Bioavailability Enhancement.

Implication of different dietary specific lipids such as phytantriol (PT) and glyceryl monooleate (GMO) on enhancing the oral bioavailability of amphotericin B (AmB) was examined. Liquid crystalline nanoparticles (LCNPs) were prepared using hydrotrope method, followed by in vitro characterization, Caco-2 cell monolayer uptake, and in vivo pharmacokinetic and toxicity evaluation. Optimized AmB-LCNPs displayed small particle size (< 210 nm) with a narrow distribution (~ 0.2), sustained drug release and high gastrointestinal stability, and reduced hemolytic toxicity. PLCNPs presented slower release, i.e., ~ 80% as compared to ~ 90% release in case of GLCNPs after 120 h. Significantly higher uptake in Caco-2 monolayer substantiated the role of LCNPs in increasing the intestinal permeability followed by increased drug titer in plasma. Pharmacokinetic studies demonstrated potential of PT in enhancing the bioavailability (approximately sixfold) w.r.t. of its native counterpart with reduced nephrotoxicity as presented by reduced nephrotoxicity biomarkers and histology studies. These studies established usefulness of PLCNPs over GLCNPs and plain drug. It can be concluded that acid-resistant lipid, PT, can be utilized efficiently as an alternate lipid for the preparation of LCNPs to enhance bioavailability and to reduce nephrotoxicity of the drug as compared to other frequently used lipid, i.e., GMO.

ε-Poly-l-Lysine/plasmid DNA nanoplexes for efficient gene delivery in vivo.

The present work addresses the development and characterization of ε-Poly-l-Lysine/pDNA polyplexes and evaluation for their improved transfection efficacy and safety as compared to polyplexes prepared using Poly-l-Lysine and SuperFect®. Self-assembling polyplexes were prepared by varying the N/P ratio to obtain the optimum size, a net positive zeta potential and gel retardation. The stability in presence of DNase I and serum was assured using gel retardation assay. Their appreciable uptake in MCF-7 and 3.5, 3.79 and 4.79-fold higher transfection compared to PLL/pDNA polyplexes and 1.60, 1.53 and 1.79-fold higher transfection compared to SuperFect®/pDNA polyplexes in MCF-7, HeLa and HEK-293 cell lines respectively, affirmed the enhanced transfection of ε-PLL/pDNA polyplexes which was well supported with in vivo transfection and gene expression studies. The <8% in vitro hemolysis and >98% viability of MCF-7, HeLa and HEK-293 cells in presence of ε-PLL/pDNA polyplexes addressed their safety, which was also ensured using in vivo toxicity studies, where hemocompatibility, unaltered levels of biochemical markers and histology of vital organs confirmed ε-PLL to be an effective and safer alternative for non-viral genetic vectors.

Improved Oral Bioavailability, Therapeutic Efficacy, and Reduced Toxicity of Tamoxifen-Loaded Liquid Crystalline Nanoparticles.

Present investigation deals with formulation and evaluation of tamoxifen (TMX)-loaded liquid crystalline nanoparticles (TMX-LCNPs) for improving oral bioavailability and safety of the existing treatment. Hexagonal Glyceryl monooleate-based TMX-LCNPs (GLCNPs) and Phytantriol-based TMX-LCNPs (PLCNPs) were prepared by dilution-through-hydrotrope method for oral administration. Oleic acid was incorporated in the lipid matrix to enhance the drug loading in the LCNPs. Optimized LCNPs displayed small particle size with a narrow distribution, sustained drug release and high gastrointestinal stability. TMX-LCNPs were found to be considerably higher cytotoxic to MCF-7 cells as compared to free TMX. Substantial fold enhancement in oral bioavailability (~7- and ~5-folds with TMX-GLCNPs and TMX-PLCNPs, respectively) was evident followed by significant reduction in tumor burden with lesser hepatotoxicity. Out of the two LCNP formulations, PLCNPs were found to be better in convalescing the disease.

Lactoferrin bioconjugated solid lipid nanoparticles: a new drug delivery system for potential brain targeting.

BACKGROUND: Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf) conjugated SLN system is first time attempted for effective brain targeting in this study. PURPOSE: Preparation of Lf-modified docetaxel (DTX)-loaded SLN for proficient delivery of DTX to brain. METHODS: DTX-loaded SLN were prepared using emulsification and solvent evaporation method and conjugation of Lf on SLN surface (C-SLN) was attained through carbodiimide chemistry. These lipidic nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro release studies. Colloidal stability study was performed in biologically simulated environment (normal saline and serum). These lipidic nanoparticles were further evaluated for its targeting mechanism for uptake in brain tumour cells and brain via receptor saturation studies and distribution studies in brain, respectively. RESULTS: Particle size of lipidic nanoparticles was found to be optimum. Surface morphology (zeta potential, AFM) and surface chemistry (FTIR) confirmed conjugation of Lf on SLN surface. Cytotoxicity studies revealed augmented apoptotic activity of C-SLN than SLN and DTX. Enhanced cytotoxicity was demonstrated by receptor saturation and uptake studies. Brain concentration of DTX was elevated significantly with C-SLN than marketed formulation. CONCLUSIONS: It is evident from the cytotoxicity, uptake that SLN has potential to deliver drug to brain than marketed formulation but conjugating Lf on SLN surface (C-SLN) further increased the targeting potential for brain tumour. Moreover, brain distribution studies corroborated the use of C-SLN as a viable vehicle to target drug to brain. Hence, C-SLN was demonstrated to be a promising DTX delivery system to brain as it possessed remarkable biocompatibility, stability and efficacy than other reported delivery systems.