Colloidal Carrier Systems Research Articles

Development of Candesartan Loaded Solid Lipid Nanoparticles by Box-Behnken Design

The primary motive behind this the present investigation was to develop and optimize the solid lipid nanoparticles formulation of candesartan to enhance solubility and dissolution rate. The prepared SLNs composed of precirol, poloxamer 188, soy lecithin, tween 80, were fabricated employing hot emulsification/ ultrasonication technique. Box-Behnken design was employed for 17 formulation batches in which 3 factors namely lipid, surfactant, and co-surfactant (precirol, poloxamer 188 and soy lecithin) tween 80 weretested at 3 levels of their concentration, i.e., low, medium and high. The effect of different levels of factors was evaluated for the particle size, entrapment efficiency and % cumulative drug release. Kinetic model fitting for candesartan solid lipid nanoparticles (SLN) formulation was done to interpret the release rate from the SLN. Optimized formulation was subjected for fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and stability studies. The mean particle size, PDI, zeta potential, entrapment efficiency, content uniformity and in-vitro drug release of optimized candesartan-loaded SLNs (CD10) were found to be 135.38 ± 3.41 nm, 0.125 ± 0.04, -18.16 ± 2.89 mV, 86.4 ± 2.35%, 99.78 ± 2.54% and 98.91 ± 0.85% respectively. The release kinetics suggested that drug release followed zero-order and release was anomalous non-fickian diffusion super case II transport. FTIR studies revealed no incompatibility between drug and excipients, SEM images exhibited nanoparticles to be more porous and in a spherical shape. Stability studies indicated good stability of the formulation. The proposed way of SLN preparation could be considered a proper method for producing a candesartan-loaded colloidal carrier system.

Overcoming the hydrophilicity of bacterial nanocellulose: Incorporation of the lipophilic coenzyme Q10 using lipid nanocarriers for dermal applications

Although used in a wide range of medical and pharmaceutical applications, the potential of the natural biopolymer bacterial nanocellulose (BNC) as drug delivery system is by far not fully exploited. Particularly, the incorporation of lipophilic drugs is still considered as an unsolved task. In the present study, the homogeneous incorporation of the lipophilic coenzyme Q10 (CoQ10) into BNC was accomplished by several post-synthesis techniques utilizing different nanoemulsions and liposomes. All colloidal carriers were in the range of about 90–120 nm with negative zeta potentials and storage stabilities up to 30 days. The biphasic drug release profiles of loaded BNC were found to be dependent on the type of colloidal carrier and the loading technique. Favorable characteristics such as high mechanical stability and high loading capacity were retained after the incorporation of the lipophilic components. Penetration studies using excised porcine skin revealed CoQ10 distributions also in deeper skin layers dependent on the type of the colloidal carrier system. In conclusion, hydrophilic BNC could be loaded with water-insoluble drugs as shown for the model drug CoQ10 by the use of lipidic colloidal carriers which offers new possibilities of application in pharmacy and medicine.

Influence of Solid Lipid Nanoparticles on Pharmaco-dynamic Activity of Poorly Oral Bioavailable Drugs

In the recent scenario, lipid nanoparticles gain much attention on the oral absorption of drugs to enhance therapeutic effectiveness after oral administration. Pharmacodynamic activity of drug mainly describes the pharmacological and therapeutic activity of drug to the biological system. Lipid nanoparticles especially solid lipid nanoparticles are made of physiological inert lipid molecules and promotes the lymphatic transport. Abundant literature is available on the effect of lipid nanoparticles and other colloidal carrier systems on the pharmacokinetic parameters of poorly bioavailable drugs, to improve their oral absorption and also respective mechanisms for the improved oral bioavailability. However, little literature is reported on the pharmacodynamic activity and the effect of dose on the pharmacodynamic activity. It is of paramount importance to assess the influence of lipid nanoparticles on pharmacotherapeutic actions of specific drug classes. Therefore, current review is mainly focused on the role of solid lipid nanoparticles on the pharmacodynamic action and advantages of the developed delivery systems with respect to pharmacodynamic activity.

C:Solid lipid nanoparticles: a prospective approach for topical drug delivery.

Solid lipid nanoparticles (SLNs) are categorized as a novel generation of nanocarriers attracting huge attention as innovative colloidal carrier systems used for drug delivery as they integrate the advantages and avoid the disadvantages of other colloidal carries such as liposomes as well as polymeric nanoparticles. SLNs are biocompatible and biodegradable carrier system made from physiological lipids, which decrease the danger of cute and chronic toxicity. Moreover, SLNs have been used as a possible attractive drug-carrier for topical drug delivery. Drug delivery to the skin is widely used for local and systemic delivery and has potentials to be improved by application of nanoparticulate formulations. This review discus on many aspects of SLNs such as their advantages and disadvantages, method of preparation, excipients influence, SLNs and topical delivery and their therapeutic applications. SLNs are promising delivery carriers for lipophilic as well as hydrophilic drugs and can form a base in the field of modern pharmaceutics.

Preparation, Statistical Optimization and Characterization of Propolis-Loaded Solid Lipid Nanoparticles Using Box-Behnken Design.

Purpose: Propolis is a resinous material obtained by honeybees with many biological and pharmacological properties which can be used for treatment of various diseases. Current study aims to formulate and characterize propolis-loaded solid lipid nanoparticles (SLNs) carrier system. Methods: The prepared SLNs, composed of glyceryl monostearate (GMS), Soy lecithin, Tween 80 and polyethylene glycol 400 (PEG 400), were fabricated employing solvent emulsification-evaporation technique. In addition, the impact of several variables including concentration ratios of GMS/Soy lecithin and PEG 400/Tween 80 along with emulsification time were evaluated on the size, polydispersity index (PDI) and zeta potential of particles. SLN formulations were optimized using Box-Behnken design. The particles were freeze dried and morphologically studied by scanning electron microscopy (SEM). The in-vitro release profile of propolis entrapped in the optimized nanoparticles was investigated. Results: The mean particle size, PDI, zeta potential, entrapment efficiency (EE) and loading efficiency (LE) of optimized propolis-loaded SLNs were found to be 122.6±22.36 nm, 0.28±0.06, -26.18±3.3 mV, 73.57±0.86% and 3.29±0.27%, respectively. SEM images exhibited nanoparticles to be non-aggregated and in spherical shape. The in-vitro release study showed prolonged release of propolis from nanoparticles. Conclusion: The results implied that the proposed way of SLN preparation could be considered as a proper method for production of propolis loaded colloidal carrier system.

SLN enriched hydrogels for dermal application: Full factorial design study to estimate the relationship between composition and mechanical properties

When considering dermal administration of cosmeceuticals and/or drugs, the stratum corneum layer of the skin, has a barrier function that limits the penetration of active substances to the targeted skin tissues. Solid lipid nanoparticles/SLNs are colloidal carrier systems, which show superiority in dermal administration of cosmeceuticals/drugs. This superiority results from the ability of the SLNs to penetrate the skin layers easily. However, the main problem in dermal administration of colloidal drug systems is the need for a suitable semisolid vehicle for application as well as patient compliance. The main purpose of this study is to investigate the relationship between hydrogels and SLNs by using 32 full factorial design which simplifies the process by establishing the relationship between variables. Two different types of gel forming agent, hydroxypropyl methylcellulose or Carbopol 934 P, in three different polymer concentration used for preparation of SLN-enriched hydrogels. Formulations evaluated for their hardness and cohesiveness by using 32 full factorial design and the optimum formulations obtained for both gelling agents. As a result, mechanical properties of hydrogels consisting either hydroxypropyl methylcellulose or Carbopol 934 P revealed promotive results for dermal application of SLNs. The type and concentration of the gel-forming agent which is selected as a semisolid carrier for lipid nanoparticles are basic parameters affecting the dermal behavior of the system.

Nanoliposomes and Tocosomes as Multifunctional Nanocarriers for the Encapsulation of Nutraceutical and Dietary Molecules.

Nanoscale lipid bilayers, or nanoliposomes, are generally spherical vesicles formed by the dispersion of phospholipid molecules in a water-based medium by energy input. The other nanoscale object discussed in this entry, i.e., tocosome, is a recently introduced bioactive carrier made mainly from tocopheryl phosphates. Due to their bi-compartmental structure, which consists of lipidic and aqueous compartments, these nanocarriers are capable of carrying hydrophilic and hydrophobic material separately or simultaneously. Nanoliposomes and tocosomes are able to provide protection and release of sensitive food-grade bioactive materials in a sustained manner. They are being utilized for the encapsulation of different types of bioactive materials (such as drugs, vaccines, antimicrobials, antioxidants, minerals and preservatives), for the enrichment and fortification of different food and nutraceutical formulations and manufacturing of functional products. However, a number of issues unique to the nutraceutical and food industry must first be resolved before these applications can completely become a reality. Considering the potentials and promises of these colloidal carrier systems, the present article reviews various aspects of nanoliposomes, in comparison with tocosomes, including the ingredients used in their manufacture, formation mechanisms and issues pertaining to their application in the formulation of health promoting dietary supplements and functional food products.

Lipid Nanoparticles and Active Natural Compounds: A Perfect Combination for Pharmaceutical Applications.

Phytochemicals represent an important class of bioactive compounds characterized by significant health benefits. Notwithstanding these important features, their potential therapeutic properties suffer from poor water solubility and membrane permeability limiting their approach to nutraceutical and pharmaceutical applications. Lipid nanoparticles are well known carrier systems endowed with high biodegradation and an extraordinary biocompatible chemical nature, successfully used as platform for advanced delivery of many active compounds, including the oral, topical and systemic routes. This article is aimed at reviewing the last ten years of studies about the application of lipid nanoparticles in active natural compounds reporting examples and advantages of these colloidal carrier systems.

Crossing the Blood-Brain Barrier: A Review on Drug Delivery Strategies for Treatment of the Central Nervous System Diseases.

Many drugs have been designed to treat diseases of the central nervous system (CNS), especially neurodegenerative diseases. However, the presence of tight junctions at the blood-brain barrier has often compromised the efficiency of drug delivery to target sites in the brain. The principles of drug delivery systems across the blood-brain barrier are dependent on substrate-specific (i.e. protein transport and transcytosis) and non-specific (i.e. transcellular and paracellular) transport pathways, which are crucial factors in attempts to design efficient drug delivery strategies. This review describes how the blood-brain barrier presents the main challenge in delivering drugs to treat brain diseases and discusses the advantages and disadvantages of ongoing neurotherapeutic delivery strategies in overcoming this limitation. In addition, we discuss the application of colloidal carrier systems, particularly nanoparticles, as potential tools for therapy for the CNS diseases.

Recent Advances in Nanocapsule: Types, Preparation Methods and Characterizatio

Nanocapsules are submicroscopic colloidal drug carrier systems consist of a liquid/solid core in which the drug, gene, protein, and other substances are incorporated into the interior cavity that is surrounded by a distinctive polymeric membrane. Polymers like collagen, albumin, and gelatin are mainly using polymers in nanocapsule formulations. Nanocapsules can serve as nano-sized drug carriers to achieve controlled release as well as efficient drug targeting. The process is used to improve the poor aqueous drug solubility, taste, stabilizing drugs by protecting the molecule from the environment, providing the desired pharmacokinetic profile, allowing controlled release, as well as facilitating oral administration. Capsules are generally prepared between the range of 100 and 1000 nm. Their release and degradation properties largely depend on the composition and the structure of the capsule walls. The dispersion stability of nanocapsules determined by the surfactant, nature of the outer coating. This review describes various facts of nanocapsule drug delivery systems in relation to the method of formulation, characterization, potential benefits and risks, and pharmaceutical applications in drug delivery.

Stabilized Production of Lipid Nanoparticles of Tunable Size in Taylor Flow Glass Devices with High-Surface-Quality 3D Microchannels.

Nanoparticles as an application platform for active ingredients offer the advantage of efficient absorption and rapid dissolution in the organism, even in cases of poor water solubility. Active substances can either be presented directly as nanoparticles or can be integrated in a colloidal carrier system (e.g., lipid nanoparticles). For bottom-up nanoparticle production minimizing particle contamination, precipitation processes provide an adequate approach. Microfluidic systems ensure a precise control of mixing for the precipitation, which enables a tunable particle size definition. In this work, a gas/liquid Taylor flow micromixer made of chemically inert glass is presented, in which the organic phases are injected through a symmetric inlet structure. The 3D structuring of the glass was performed by femtosecond laser ablation. Rough microchannel walls are typically obtained by laser ablation but were smoothed by a subsequent annealing process resulting in lower hydrophilicity and even rounder channel cross-sections. Only with such smooth channel walls can a substantial reduction of fouling be obtained, allowing for stable operation over longer periods. The ultrafast mixing of the solutions could be adjusted by simply changing the gas volume flow rate. Narrow particle size distributions are obtained for smaller gas bubbles with a low backflow and when the rate of liquid volume flow has a small influence on particle precipitation. Therefore, nanoparticles with adjustable sizes of down to 70 nm could be reliably produced in continuous mode. Particle size distributions could be narrowed to a polydispersity value of 0.12.

Design and Development of Valsartan Loaded Nanostructured Lipid Carrier for the Treatment of Diabetic wound Healing

Diabetes mellitus is a group of metabolic diseases identified by hyper glycaemia that results from defects in insulin secretion, insulin action or both. It can also be referred as metabolic disorder. The main objective of this research is to enhance the protection of wound healing from the valsartan loaded Nanostructure Lipid carrier. Valsartan is the angiotensin II antagonist drug, which is of BCS class II category. Nanostructure lipid carrier is a colloidal carrier system which is having many advantages such as improvement in Bioavailability, Increase in the solubility and therapeutic efficacy. The prepared Nanostructure lipid carrier was consisting of palmitic acid as solid lipid and soya oil as liquid lipid were prepared by melt emulsification method. Optimization and Characterization of Valsartan loaded NLCs have been done by DSC, FT-IR, Particle size, Zeta potential, Scanning Electron microscopy, Stability study, Entrapment efficiency, Release kinetics and In-vitro drug release studies. The In-vivo have also been done for the treatment of Diabetic wound healing. In Conclusion, it is shown that the valsartan loaded Nanostructure lipid carrier formulation was very effectively for the treatment of Diabetic wound Healing.

Biomedical applications of microemulsion through dermal and transdermal route

Microemulsions are thermodynamically stable, transparent, colloidal drug carrier system extensively used by the scientists for effective drug delivery across the skin. It is a spontaneous isotropic mixture of lipophilic and hydrophilic substances stabilized by suitable surfactant and co-surfactant. The easy fabrication, long-term stability, enhanced solubilization, biocompatibility, skin-friendly appearance and affinity for both the hydrophilic and lipophilic drug substances make it superior for skin drug delivery over the other carrier systems. The topical administration of most of the active compounds is impaired by limited skin permeability due to the presence of skin barriers. In this sequence, the microemulsion represents a cost-effective and convenient drug carrier system which successfully delivers the drug to and across the skin. In the present review work, we compiled various attempts made in last 20 years, utilizing the microemulsion for dermal and transdermal delivery of various drugs. The review emphasizes the potency of microemulsion for topical and transdermal drug delivery and its effect on drug permeability.

Interactions of Cationic Lipids with DNA: A Structural Approach.

Colloidal nucleic acid carrier systems based on cationic lipids are a promising pharmaceutical tool in the implementation of gene therapeutic strategies. This study demonstrates the complex behavior of DNA at the lipid-solvent interface facilitating structural changes of the lyotropic liquid-crystalline phases. For this study, the structural properties of six malonic acid based cationic lipids were determined using small- and wide-angle X-ray scattering (SAXS and WAXS) as well as differential scanning calorimetry (DSC). Selected lipids (lipid 3 and lipid 6) with high nucleic acid transfer activity have been investigated in detail because of the strong influence of the zwitterionic helper lipid 1,2-di(9 Z-octadecenoyl)- sn-glycero-3-phosphoethanolamine (DOPE) on the structural properties as well as of the complex formation of lipid-DNA complexes (lipoplexes). In the case of lipid 3, DNA stabilizes a metastable cubic mesophase with Im3 m symmetry and an Im3 m Qαc lipoplex is formed, which is rarely described for DNA lipoplexes in literature. In the case of lipid 6, a cubic mesophase with Im3 m symmetry turns into a fluid lamellar phase while mixing with DOPE and complexing DNA.

Thymoquinone a Potential Therapeutic Molecule from the Plant Nigella sativa: Role of Colloidal Carriers in its Effective Delivery.

From the past few decades, remarkable awareness has laid on the use of herbal medicines in pharmaceutical research. Thymoquinone (TQ), the main chemical constituent of Nigella Sativa (NS) plant, has been extensively explored, and revealed an array of therapeutic benefits, in different in vitro, and in vivo conditions. This review provides brief outline of the diverse therapeutics actions of TQ, and NS, viz. anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, gastroprotective, hepato-protective, anti-microbial and anti-histaminic. Besides, a special emphasis has given on the use of colloidal drug delivery systems exploited hitherto, for the effective delivery of TQ and NS. The main objective of the review was to include an intensive patent literature, available on TQ and NS, for its usefulness in different therapeutic conditions. We embarked an organized search of bibliographic databases for peer-reviewed research literature and patent databases. The characteristics of screened papers were described, and a rational qualitative content analysis approach was applied to analyze the interventions and findings of included studies using a theoretical framework. In the past, various studies have carried out which undoubtedly vouch for the multifarious therapeutic roles of TQ in an array of different diseases. More than 670 research papers and around 50 review articles are available on TQ and NS in PubMed database until now, suggesting its high significance. Around 12 review articles published only on the anticancer potential, while the others on its anti- inflammatory and anti-oxidant potential. Around 120 papers included in the review revealed the therapeutic benefits of TQ. In addition to this, an intensive patent literature is also available on TQ and NS, for its usefulness in different therapeutic conditions. The findings of this review confirm the effectiveness of TQ in various pathologies viz. inflammation, cancer, diabetes, gastric, hepatic, microbial and allergies. However, the complete clinical benefit of TQ has not yet been realized, owing to its poor biopharmaceutical properties. Nevertheless, colloidal drug delivery carrier systems, could be impending in bringing forth this potential molecule to reality.

Therapeutic potential of drug delivery by means of lipid nanoparticles: reality or illusion?

Solid lipid nanoparticles (SLN) are colloidal drug carrier systems that contribute several properties required from a sophisticated drug delivery system for increasing drug bioavailability and providing effective therapy. Many advantages of SLN have been reported over traditional dosage forms and their colloidal counterparts in the studies since the early 1990s. They were optimized for oral drug delivery for the first time. The first SLN formulations were produced by reducing the particle size of solid lipid microparticles by spray congealing technique in the late 1980s. Then, studies have been continued investigating for their different administration routes else including parenteral, transdermal, ocular, nasal, respiratory etc. Their foremost qualifications such as their biocompatible nature and high drug entrapment efficiency make them promising colloidal drug carrier systems for the effective treatment of serious disasters like genetic disorders and cancer. In this review, therapeutic potential of drug delivery of SLN and nanostructured lipid carriers (NLC, the second generation of SLN) are summarized considering researches and patents on their administration via different routes and their preparations in the pharmaceutical market.

Optically monitored segmented flow for controlled ultra-fast mixing and nanoparticle precipitation

Nanoparticles of drugs or colloidal carrier systems are capable of providing substantial advantages for drug bioavailability, but manufacturing nanoparticulate drugs or drug carriers remains a challenge because traditional mechanical or chemical batch mode processes might lack precise control of nanoparticle sizes. Microfluidic approaches are believed to give advantages but often do not provide chemically inert environments and lack controllable operation. Here, segmented flow devices with symmetrical design for centered organic phase injection and for nanoparticle precipitation in transparent and chemically inert glass microchannels are presented. Femtosecond laser fabrication was used to structure borosilicate glass wafers with hydrophilic microchannels of nearly circular cross section. They allow for ultra-fast mixing of solvents with aqueous fluids and subsequent precipitation of poorly water soluble drug nanoparticles or colloidal carrier particles. The best results for mixing and controlled precipitation were obtained with flow focusing and gas segmentation occurring at the same channel intersection point. In such systems, early interdiffusion of the solvent and aqueous solution before ultra-fast convective mixing in the plug is suppressed. A novel optical analysis technique revealed that the speed of mixing can be well controlled by simply adjusting the volume flow rate of the gas phase where changes in the liquid flow rate have practically no influence. In a controlled and stable Taylor flow, smallest plug volumes of 3.8 nl can be generated, which allows complete mixing in 9 ms. The production of lipid nanoparticles down to a diameter of 74 nm could already be demonstrated.

Carrier characteristics influence the kinetics of passive drug loading into lipid nanoemulsions

Passive loading as a novel screening approach is a material-saving tool for the efficient selection of a suitable colloidal lipid carrier system for poorly water soluble drug candidates. This method comprises incubation of preformed carrier systems with drug powder and subsequent determination of the resulting drug load of the carrier particles after removal of excess drug. For reliable routine use and to obtain meaningful loading results, information on the kinetics of the process is required. Passive loading proceeds via a dissolution-diffusion-based mechanism, where drug surface area and drug water solubility are key parameters for fast passive loading. While the influence of the drug characteristics is mostly understood, the influence of the carrier characteristics remains unknown. The aim of this study was to examine how the lipid nanocarriers’ characteristics, i.e. the type of lipid, the lipid content and the particle size, influence the kinetics of passive loading. Fenofibrate was used as model drug and the loading progress was analyzed by UV spectroscopy. The saturation solubility in the nanocarrier particles, i.e. the lipid type, did not influence the passive loading rate constant. Low lipid content in the nanocarrier and a small nanocarrier particle size both increased passive loading speed. Both variations increase the diffusivity of the nanocarrier particles, which is the primary cause for fast loading at these conditions: The quicker the carrier particles diffuse, the higher is the speed of passive loading. The influence of the diffusivity of the lipid nanocarriers and the effect of drug dissolution rate were included in an overall mechanistic model developed for similar processes (A. Balakrishnan, B.D. Rege, G.L. Amidon, J.E. Polli, Surfactant-mediated dissolution: contributions of solubility enhancement and relatively low micelle diffusivity, J. Pharm. Sci. 93 (2004) 2064–2075). The resulting mechanistic model gave a good estimate of the speed of passive loading in nanoemulsions. Whilst the drug’s characteristics – apart from drug surface area – are basically fixed, the lipid nanocarriers can be customized to improve passive loading speed, e.g. by using small nanocarrier particles. The knowledge of the loading mechanism now allows the use of passive loading for the straightforward, material-saving selection of suitable lipid drug nanocarriers.

Retarder action of isosorbide in a microemulsion for a targeted delivery of ceramide NP into the stratum corneum.

Ceramide [NP] is an integral component of the stratum corneum (SC) lipid matrix and is capable of forming tough and stable lamellar structures. It was proven, that in skin diseases as psoriasis or atopic dermatitis different ceramide (CER) classes, including [NP], are degraded. It is obvious that topically application of CER on impaired skin is useful for repairing the skin barrier but a tendency for low penetration due to its poor solubility in conventional dosage forms was observed. Therefore, a stable and physiologic compatible colloidal carrier system, a microemulsion (ME), was developed and characterized. The increasing knowledge of the new colloidal systems in this last decade shows their benefits in dermal application. Isosorbide (Polysorb P) was incorporated into the ME developed. It was expected that Polysorb P has a retarder potential in order to accumulate the CER in the SC, the outermost layer of the skin. Thereby the CER [NP] would be able to interact with the affected skin layers to strengthen the skin barrier. The release and penetration behavior of the CER [NP] from the ME was assessed ex vivo in a Franz diffusion cell. The results of the study showed that CER [NP] penetrate largely in the upper layers of the skin (from SC to stratum basale), which was the desired region. A recovery in the acceptor could not be detected that underlines an accumulation in upper layers. Furthermore, significantly increased values for the SC for the ME with retarder were not received. No differences in the concentrations of CER [NP] were observed. However, the toxicity of MEs was investigated using heńs egg test chorioallantoic membrane (HET-CAM). For the isosorbide-containing ME no difference was obtained in comparison to the non-containing. The results showed that both MEs are safe to be used on the skin for the controlled penetration of CER [NP] into the skin. The isosorbide had no effect on the irritating effect as well as on the penetration of the used CER.

Enhanced Anti Arthritic Potential of Tacrolimus by Transdermal Nanocarrier System

Current work entails the development and assessment of a well-tolerated colloidal carrier system containing immunosuppressant drug tacrolimus (TL) for transdermal delivery to study its efficacy against arthritis. TL-NEs of different composition from phase diagram were prepared by high sheer homogenization and a comprehensive physico-chemical characterization of the novel NEs were performed using different techniques in order to get most optimum NE. Optimized NE was incorporated in to carbopol-934 gel and subjected to ex vivo skin permeation studies, droplet size analysis, zeta potential measurement, TEM examination, Rheology, and stability study. Moreover, we have evaluated the in vivo anti arthritic potential of same formulation and compared it with a marketed ointment (Protopic®, 0.03%) for the first time. Optimized TL-NG formulation composed of Capryol 90 (5.0% w/w), tween-20 (15.0% w/w), Transcutol HP (7.5% w/w), water (72.5%) w/w, carbopol-934 (1.0%) and found to have permeation flux (68.88 μg/cm2/h), release (1621.46 μg/24 h), small droplet size (12.72 nm), and viscosity of 1.07 Pa-s. The results of ZP indicated that formulation was stable and shelf life at room temperature was calculated as 1.59 years. The in vivo investigation demonstrated direct evidence on significant reduction (41.80%) in inflammation over a period of 24 h. On the basis of these preliminary finding, we conclude that developed TL-NG has good anti-inflammatory action and may provide promising perspective for treatment of Arthritis.