NLC Formulation Research Articles

Antipsoriatic Effect of Silymarin NLCs Based Gel: In Vitro and In Vivo Activity.

Psoriasis is a chronic inflammatory disorder affecting over 100 million people, requires long-term therapy. Current treatments offer only symptomatic relief. However, phytoconstituents-based therapies like Silymarin (SLM) have shown promising effects. The study aims to develop, optimize, and evaluate a novel stable SLM NLC gel to improve anti-psoriatic activity by enhancing its permeability and retention into the dermal layer. SLM NLC formulation was prepared and optimized using 32 full factorial designs. The formulation was evaluated for the particle size, PDI, zeta potential, and % entrapment efficiency, evaluated by Transmission electron microscopy and thermal analysis. The freeze dried and prepared NLC-loaded gel was evaluated for physicochemical parameters, ex-vivo, and in-vivo studies. SLM-loaded NLC shows 624nm particle size, 0.41 PDI, 92.95% entrapment efficiency, and -31.6mV zeta potential. The sphere form of NLCs was confirmed using TEM. Controlled drug release was observed in ex vivo studies, low PASI score compared to disease control. Further, the levels of IL-6, TNF-α, and NF-κB were also reduced. The results are supported by histopathology showing minimal parakeratosis indicated in the SLM NLC-treated group. Prepared NLC-based shows enhance topical penetration and decrease the thickness of psoriatic plaques in the in vivo study.

Pharmacokinetics and Pharmacodynamics of a Nanostructured Lipid Carrier Co-Encapsulating Artemether and miRNA for Mitigating Cerebral Malaria.

Cerebral malaria (CM), a severe neurological pathology caused by Plasmodium falciparum infection, poses a significant global health threat and has a high mortality rate. Conventional therapeutics cannot cross the blood-brain barrier (BBB) efficiently. Therefore, finding effective treatments remains challenging. The novelty of the treatment proposed in this study lies in the feasibility of intranasal (IN) delivery of the nanostructured lipid carrier system (NLC) combining microRNA (miRNA) and artemether (ARM) to enhance bioavailability and brain targeting. The rational use of NLCs and RNA-targeted therapeutics could revolutionize the treatment strategies for CM management. This study can potentially address the challenges in treating CM, allowing drugs to pass through the BBB. The NLC formulation was developed by a hot-melt homogenization process utilizing 3% (w/w) precirol and 1.5% (w/v) labrasol, resulting in particles with a size of 94.39 nm. This indicates an effective delivery to the brain via IN administration. The results further suggest the effective intracellular delivery of encapsulated miRNAs in the NLCs. Investigations with an experimental cerebral malaria mouse model showed a reduction in parasitaemia, preservation of BBB integrity, and reduced cerebral haemorrhages with the ARM+ miRNA-NLC treatment. Additionally, molecular discoveries revealed that nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and Interleukin-6 (IL-6) levels were reduced in the treated groups in comparison to the CM group. These results support the use of nanocarriers for IN administration, offering a viable method for mitigating CM through the increased bioavailability of therapeutics. Our findings have far-reaching implications for future research and personalized therapy.

Formulation of Topical Itraconazole Nanostructured Lipid Carriers (Nlc) Gel for Onychomycosis

Itraconazole is a triazole antifungal agent that is synthesised. Itraconazole has been manufactured into a variety of pharmacological formulations and administered by a variety of ways. Itraconazole pills are used to treat pulmonary fungal infections that can spread throughout the body. Because Itraconazole is not yet officially listed in any pharmacopoeia, only a few procedures for quality control and stability testing in pharmaceutical formulations have been published. The development of itraconazole-loaded nanostructured lipid carriers (ITZ-NLC). Itraconazole NLC have been successfully developed. Itraconazole topical NLC developed for the treatment of onychomycosis does not exist, according to my survey.The development and evaluation of stable itraconazole topical gel formulations proved successful. Itraconazole NLC was produced utilising the microemulsion method, indicating the viability of adopting this method as a continuous manufacturing tool for NLC formulation. Further, the ITZ- NLC was incorporated in the gelling agent and we evaluated it under specific parameters.

Formulation, Optimization and Characterization of Bupropion Hydrochloride Loaded Nanostructured Lipid Carriers for Intra-Nasal Administration: An Approach to Management of Smoking Cessation

Background: Tobacco smoking is a major factor leading to cardiovascular diseases. About 48% of cardiovascular diseases occur due to cigarette smoking. Bupropion hydrochloride is a non-nicotine treatment for smoking cessation. The existing marketed formulation of bupropion has limitations, like low bioavailability and extensive first-pass metabolism. In order to boost the bioa-vailability and increase the brain biodistribution of the drug, a colloidal drug delivery system, like nanostructured lipid carriers, is employed. Methods: NLC formulation was prepared using the microemulsion technique and an optimized formula was developed using a three-level factorial design. Results: The particle size of the optimized formulation was 162 nm, the polydispersity index was 12.2%, and the zeta potential was -29.0mV. Entrapment efficiency was found to be 41.2%. SEM images show that these NLCs are spherical. In vitro drug release study was conducted, and at the end of 72 hours, 50% of the drug was released, indicating the sustained release of the drug. Histo-pathological studies were conducted using goat nasal mucosa, and results indicated the NLC formu-lation as non-toxic for intranasal administration. Conclusion: Thus, through the intra-nasal route, an increased concentration of drug can be deliv-ered to the brain via the olfactory pathway, thereby improving the therapeutic effect and exhibiting better patient compliance in smoking cessation.

Berberine loaded dermal quality by design adapted chemically engineered lipid nano-constructs-gel formulation for the treatment of skin acne

The study's purpose intended to develop and optimize an NLC formulation for topical berberine administration with increased skin acne efficacy. The “three-parameters, three-level Box-Behnken design” was employed to improve the formulation based on vesicle size, PDI, and encapsulation efficiency. In-vitro profile for drug release, skin penetration investigation using confocal microscopy, skin irritation, anti-inflammatory, and anti-acne studies were performed on the optimized formulation. The vesicles with a size of 132.5 ± 10.34 nm, PDI of 0.224 ± 5.12, and entrapment efficiency of 85.956 ± 5.78% were found in the optimized formulation. The optimized formulation had spherical vesicles, according to TEM imaging. In vitro release studies showed that final optimized NLC formulation has cumulative release of drug (72.675 ± 3.686%), which was significantly greater as compared to NLC gel formulation (48.354 ± 4.893%). Thermo-analytical studies of NLCs formulation determined smooth drug interaction via rat skin membrane. Confocal microscopy revealed that, rhodamine-NLC formulation was traceable up to 54.9 μm across skin of rats, while solution of rhodamine penetrated only up to 20.4 μm of rat skin. Skin irritation study further showed significantly lower irritation level of skin (erythema: 0.50.231 and edema: 0.50.320) by applying optimized NLC-gel formulation compared to the control irritant. Furthermore, in comparison to the positive control, the anti-acne study demonstrated a decrease in all acne parameters, in addition to higher effectiveness over the commercially available formulation. These findings suggest that developed berberine loaded NLC gel could be a promising vehicle for the safe and effective topical administration of drugs to treat acne vulgaris.

QbD based formulation optimization of semi-solid lipid nanoparticles as nano-cosmeceuticals

Nano-cosmeceuticals are cosmetic formulations containing nano-drug delivery systems to carry cosmetic active molecules to the relevant skin tissues. The purpose of this research is to develop and optimize the semi-solid nanostructured lipid carriers for caffeine delivery to the deeper skin layers. It is also aimed to achieve a novel nanotechnology-based cosmeceutical formulation with predetermined quality. Hence both caffeine and argan oil encapsulated semi-solid NLCs were developed by following QbD steps. An artificial neural network (ANN) program was employed to reach optimized formulation with desired critical quality attributes (CQAs). The optimized formulation suggested by the ANN exhibited a particle size of 186.5 nm with a PDI value of 0.208 and the occlusion factor of the optimized formulation reached 50.25% after 12 h. A high level of similarity was obtained between the CQAs predicted by ANN and experimental results for the optimum formulation. The present study concluded that the novel caffeine-loaded semi-solid NLC formulation which also contains argan oil is a promising candidate for local treatment of cellulite and it may possess the measurable skin effect. Moreover; a high-quality nano-cosmeceutical product was obtained with the help of artificial intelligence by following QbD steps for the first time to the best of our knowledge.

Development and Validation of UV Spectroscopic Technique for the Assessment of Dopamine to Prepare NLC Formulation in the Therapy of Parkinson’s Disease

The easy, rapid, accurate, and specific demonstrating UV spectroscopic process for validation of Dopamine in pure bulk and nanoformulation has been developed. Dopamine works as a precursor in a biosynthetic pathway of epinephrine and nor-epinephrine. Mainly it is a neurotransmitter in the central nervous systems and peripheral nervous systems to convey the signals from one neuron to another neuron as a biological messenger. The deficiency of DOPA in cells causes Parkinson’s disease. The major aim in the therapy of Parkinson’s disease is to increase the normal concentration of dopamine in the brain but dopamine is unable to reach the brain owing to the inability of dopamine to cross the blood brain barrier hence NLC of DOPA is a new approach of drug delivery without any modification to the drug molecule. There is no specific UV spectroscopy technique that has been described for the validation and assessment of DOPA in bulk to prepare dopamine loaded NLC formulation (NLC-DOPA). Current work has shown the drug characterization to confirm the identification and compatibility of the drug with lipids by the DSC and FTIR. The UV Spectroscopy technique has been developed and validated to determine dopamine in bulk and NLC-DOPA formulation as continued via the International Conference of Harmonization guidelines. The developed method follows the beer’s law in a series of 10-70 μg/ml along with a correlation coefficient of R2 = 0.999 at the wavelength of 280 nm. The % Assay of dopamine was found to be near to 100 %. The % recovery of developed method was found to be accurate in the form of Mean ± %RSD and the method was found to be precise at differential day variation (Mean ± % RSD). The LOD and LOQ were performed appropriately. This method has been productively used to find out the amount of dopamine hydrochloride available in the formulation.

Formulation and intestinal absorption of naringenin loaded nanostructured lipid carrier and its inhibitory effects on nonalcoholic fatty liver disease

In this study, we prepared naringenin (NGN) loaded nanostructured lipid carrier (NGN-NLC) and investigated its characterizations, transepithelial transport, intestinal absorption and inhibitory effects on nonalcoholic fatty liver disease (NAFLD) induced by a methionine choline deficient (MCD) diet in mice. The NGN-NLC, prepared by a method of emulsion-evaporation plus low temperature-solidification, displayed high drug loading capacity of 22.5 ± 1.7%. Compared to the NGN crude drug, the NGN-NLC, at an equal NGN dose, improved NGN release rate by 3.5-fold and elevated NGN transepithelial transport and intestinal absorption through enhancing intracellular transport of clathrin pathway and escaping p-gp efflux; at an 8-fold lower NGN dose, showed comparable pharmacokinetic parameters, but elevated liver NGN distribution by 1.5-fold, reduced MCD diet-induced hepatic lipid deposition by 3-fold. These results suggest that the NLC formulation significantly increased the inhibitory effects of NGN on NAFLD because of the improved drug release rate, transepithelial transport and intestinal absorption, and the elevated oral bioavailability and liver NGN distribution.

Enhanced delivery of melatonin loaded nanostructured lipid carriers during in vitro fertilization: NLC formulation, optimization and IVF efficacy.

In this study, the potential of melatonin hormone loaded in nanostructured lipid carriers (Mel-NLCs) in the in vitro fertilization (IVF) environment is investigated by measuring the oocyte maturation, the two-pre-nucleus embryo development, the two-cell stage embryo development, and blastocyst production on the oocytes of mice. Mel-NLCs are prepared using the hot homogenization-ultrasonication method. A response surface method is utilized to determine the best independent variables to obtain nanoparticles with a small particle size and high hormone entrapment efficiency. The optimized nanoparticles have a particle size of 119 nm with a polydispersity index of 0.09 and hormone entrapment efficiency of 94%. Characterization results such as TEM and AFM analysis confirm the spherical and relatively uniform structure of the optimal sample. FTIR and XRD analyses indicate that the hormone is properly loaded within the amorphous nanostructure. Drug release from NLC under the in vitro environment exhibits a biphasic domain including burst release in the first 2 hours and the controlled release in 48 h 92% of the drug is released from nanoparticles in 48 hours, but the same amount of hormone is released from the marketed drug suspension during 2 hours. Results of IVF experiments reveal that the nanostructured form has a positive effect on all IVF parameters compared to the free form of the hormone. In addition, using the hormone nanostructured form can reduce the dosage of the melatonin free form with the same efficacy in the IVF environment. Finally, the nanostructured form of melatonin based on NLC nanostructure can be a good candidate for application in IVF media.

QbD guided early pharmaceutical development study: Production of lipid nanoparticles by high pressure homogenization for skin cancer treatment

This research attempts to bring together the positive aspects of lipid nanoparticles and Quality by Design (QbD) approach for developing a novel drug delivery system for skin cancers and aktinic keratosis. Lipid nanoparticles which is one of the most efficacious options for topical treatment of skin diseases were prepared due to their ability to overcome the complex structure of skin barrier and to enhance the skin penetration. Since the formulation development contains complex variables of active ingredients, raw materials or production method; all the variables of the product should be elaborated. QbD approach which refers to design and develop formulations and manufacturing processes to maintain the prescribed product quality was also successfully adopted to achieve a time- and cost-saving process ensuring a high-quality product.5-Fluorouracil (5-FU) loaded lipid nanoparticles, both solid lipid nanoparticles and nanostructured lipid carriers, were developed and characterized by following QbD steps. Optimal lipid nanoparticle formulation with guaranteed quality which was within the design space has been reached through the artificial neural networks. The optimal lipid nanoparticle formulation which is a NLC formulation with a mean particle size of 205,8 ± 9,34 nm, narrow size distribution (0.279 ± 0.01) and negative zeta potantial −30,20 ± 0,92 was produced by high pressure homogenization method. Cytotoxicity profiles of the optimal NLC was determined by cell culture studies on epidermoid carcinoma cells and human keratinocyte cells. Optimal NLC showed significantly higher anticancer effect on epidermoid carcinoma cells than free 5-FU and also less cytotoxicity towards human keratinocyte cells. Optimal NLC was formulated in hydrogel formulation for ease of application which has suitable occlusive and mechanical properties, viscocity and pH for patient complience. The cumulative amount of 5-FU in dermal tissues of rat skin was found 20.11 ± 2.14 μg/cm2 and 9.73 ± 0.87 μg/cm2 after application of NLC enriched hydrogel and 5-FU hydrogel respectively.In conclusion, this study showed that a time and cost saving process ensuring a high-quality product can be obtained by QbD guided formulation development study with the help of artificial neural networks. A novel semisolid dosage form enriched by NLC which is promising for topical treatment of skin cancers was developed.

Development of Betamethasone Dipropionate-Loaded Nanostructured Lipid Carriers for Topical and Transdermal Delivery

IntroductionBetamethasone dipropionate is a highly effective corticosteroid anti-inflammatory. However, the main drawback of its topical use is the limited skin penetration into deeper skin layers. Also, its systemic use has shown many side effects.ObjectiveThe goal of this research was to formulate betamethasone dipropionate in nanostructured lipid carriers (NLC) formulae that contain oleic acid to aid its penetration to deeper skin layers and to aid absorption to local regions upon topical application.MethodsNLC formulae were prepared by high shear homogenization then sonication. Formulae were characterized for their particle size, size distribution, electric potential, occlusion factor, entrapment efficiency, drug loading, transmission electron microscopy, in vitro drug release, and ex vivo skin penetration. Compatibility of ingredients with drug was tested using differential scanning calorimetry. Formulae were shown to have appropriate characteristics. NLC formulae were superior to traditional topical formulation in drug release.ResultsUpon testing ex vivo skin penetration, betamethasone dipropionate prepared in NLC formulae was shown to penetrate more efficiently into skin layers than when formulated as a traditional cream. NLC formulation that contained higher percentage of oleic acid showed higher penetration and higher amount of drug to pass through skin.ConclusionIn general, NLC with lower oleic acid percentage was shown to deliver betamethasone dipropionate more efficiently into deeper skin layers while that of a higher oleic acid percentage was shown to deliver the drug more efficiently into deeper skin layers and through the skin, transdermally.

Topical Nanostructured Lipid Carrier Based Hydrogel of Mometasone Furoate for the Treatment of Psoriasis.

The aim of the present study was to develop and evaluate nanostructured lipid carrier based topical hydrogel of mometasone furoate for the treatment of psoriasis. Drug loaded NLCs were successfully developed by microemulsion technique. Pseudo ternary phase diagrams were constructed using different combinations of surfactant and co-surfactants to study the microemulsion existence range. Different compositions were selected from the phase diagram showing maximum microemulsion region and were converted into NLCs by dilution in water (1:20). The optimized formulation was characterised for droplet size, zeta potential, entrapment efficiency and morphology was studied using Transmission Electron Microscopy. Ex vivo permeation studies were carried out using Wistar rat skin. The potential of this formulation in treating psoriatic inflammation was studied using imiquimod induced skin inflammation animal model. The optimized formulation (F4) has droplet size of 163.2±0.522 nm, zeta potential - 0.086±0.099 mV and entrapment efficiency of 60.0±0.187%. Transmission electron microscopy confirmed spherical shape of nanostructured lipid carrier. Carbopol 940 was used to convert NLC dispersion into NLC based hydrogel to improve its viscosity for topical administration. Drug permeation studies showed prolonged drug release from the NLC based gel as compared to marketed formulation following Higuchi release kinetics. The skin deposition of MF loaded NLC based hydrogel was found to 2.5 fold higher than marketed formulation with primary skin irritation index of 0.20. In vivo studies showed complete clearance of parakeratosis by treatment with the prepared NLC formulation. Accelerated stability studies signify high robustness scale of optimized formulation under one month storage period. The prepared NLC based formulation has proved to be a promising carrier system for the treatment of psoriasis.

Quercetin Loaded Nanostructured Lipid Carriers for Nose to Brain Delivery: In Vitro and In Vivo Studies

The main objective of the study was to utilize potential of nanostructured lipid carriers of the quercetin for direct nose to brain delivery of drug as tool for the targeted delivery. The aim of this study was to prepare and characterize quercetin loaded NLC and to study its brain distribution. Novel QUE-NLCs were formulated. NLC Formulation was evaluated for various physicochemical properties such as particle size, zeta potential, drug loading, percent entrapment efficiency, morphology, in vitro drug release, and histopathology. The size of the QUE-NLC was about 118.2nm with poly dispersity index of 0.220 and zeta potential of -20.1 mV. Nose to brain distribution studies were performed using wistar rats.QUE-NLC exhibited sustained delivery of drug. Significant targeting to brain was achieved when compare to quercetin.The result showed that NLCs might be the promising approach for the nose to brain delivery of quercetin.

Skin Localization of Lipid Nanoparticles (SLN/NLC): Focusing the Influence of Formulation Parameters.

In this study, fluorescein labeled SLN and NLC formulations were prepared for improving the dermal distribution of the hydrophilic active ingredients and for enhancing the skin penetration. To determine skin distribution of the lipid nanoparticles ex-vivo penetration/ permeation experiments were performed using full thickness rat skin by means of Franz diffusion cells. Studies on the localization of fluorescence labeled nanoparticles were performed by confocal laser scanning microscopy (CLSM). Cellular uptake studies were performed on human keratinocyte cell line (HaCaT) and visualized by fluorescence microscope. Both tissue and cell uptake were also quantitatively determined by means of fluorimetric method in the skin extract or cell extract. Both imaging and quantification studies suggest that the dermal localization of the lipid nanoparticles depends on their dimensions and particle size distribution. The CLSM images clearly show that the Tripalmitin based lipid nanoparticles have higher accumulation in the skin. It is possible to overcome the stratum corneum barrier function with T-NLC05 coded lipid nanoparticle formulation. Additionally cellular uptake of this NLC formulation is time dependent. Conclusıon: It can be concluded that this formulation is promising for treating local skin disorders without systemic side effects. On the other hand obtained results suggest that optimum formulation (T-NLC05) might be an interesting option even for novel cosmetic products.

Improved pharmacokinetics and antihyperlipidemic efficacy of rosuvastatin-loaded nanostructured lipid carriers

In the present study, rosuvastatin calcium-loaded nanostructured lipid carriers were developed and optimized for improved efficacy. The ROS-Ca-loaded NLC was prepared using melt emulsification ultrasonication technique and optimized by Box–Behnken statistical design. The optimized NLC composed of glyceryl monostearate (solid lipid) and capmul MCM EP (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and tween 80 (1%) as surfactant. The mean particle size, polydispersity index (PDI), zeta potential (ζ) and entrapment efficiency (%) of optimized NLC formulation was observed to be 150.3 ± 4.67 nm, 0.175 ± 0.022, −32.9 ± 1.36 mV and 84.95 ± 5.63%, respectively. NLC formulation showed better in vitro release in simulated intestinal fluid (pH 6.8) than API suspension. Confocal laser scanning showed deeper permeation of formulation across rat intestine compared to rhodamine B dye solution. Pharmacokinetic study on female albino Wistar rats showed 5.4-fold increase in relative bioavailability with NLC compared to API suspension. Optimized NLC formulation also showed significant (p < 0.01) lipid lowering effect in hyperlipidemic rats. Therefore, NLC represents a great potential for improved efficacy of ROS-Ca after oral administration.

Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs.

The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery.

Carvedilol nano lipid carriers: formulation, characterization and in-vivo evaluation

The purpose of this study was to develop Carvedilol nanostructured lipid carriers (CAR-NLCs) using stearic acid and oleic acid as lipid, and to estimate the potential as oral delivery system for poorly water soluble drug. The particle-size analysis revealed that all the developed formulations were within the nanometer range. The EE and loading were found to be between 69.45–88.56% and 9.58–12.56%, respectively. The CAR–NLCopt showed spherical morphology with smooth surface under transmission electron microscope (TEM). The crystallization of the drug in NLC was investigated by powder X-ray diffraction and differential scanning calorimetry (DSC) and revealed that the drug was in an amorphous state in the NLC matrix. The ex vivo gut permeation study showed many folds increment in the permeation of CAR-NLCs compared to Carvedilol suspension (CAR-S). The oral bioavailability study of CAR was carried out using Wistar rats and relative bioavailability of CAR–NLCopt was found to be 3.95 fold increased in comparison with CAR-S. In vivo antihypertensive study in Wistar rats showed significant reduction in mean systolic BP by CAR-NLCopt vis-à-vis CAR-S (p < 0.05) owing to the drug absorption through lymphatic pathways. In conclusion, the NLC formulation remarkably improved the oral bioavailability of CAR and demonstrated a promising perspective for oral delivery of poorly water-soluble drugs. The promising findings in this investigation suggest the practicability of these systems for the enhancement of bioavailability of CAR.

Optimization of artemether-loaded NLC for intranasal delivery using central composite design

The objective of the study was to optimize artemether-loaded nanostructured lipid carriers (ARM-NLC) for intranasal delivery using central composite design. ARM-NLC was prepared by microemulsion method with optimized formulation having particle size of 123.4 nm and zeta potential of −34.4 mV. Differential scanning calorimetry and powder X-ray diffraction studies confirmed that drug existed in amorphous form in NLC formulation. In vitro cytotoxicity assay using SVG p12 cell line and nasal histopathological studies on sheep nasal mucosa indicated the developed formulations were non-toxic and safe for intranasal administration. In vitro release studies revealed that NLC showed sustained release up to 96 h. Ex vivo diffusion studies using sheep nasal mucosa revealed that ARM-NLC had significantly lower flux compared to drug solution (ARM-SOL). Pharmacokinetic and brain uptake studies in Wistar rats showed significantly higher drug concentration in brain in animals treated intranasally (i.n.) with ARM-NLC. Brain to blood ratios for ARM-NLC (i.n.), ARM-SOL (i.n.) and ARM-SOL (i.v.) were 2.619, 1.642 and 0.260, respectively, at 0.5 h indicating direct nose to brain transport of ARM. ARM-NLC showed highest drug targeting efficiency and drug transport percentage of 278.16 and 64.02, respectively, which indicates NLC had better brain targeting efficiency compared to drug solution.