Nanostructured Lipid Carriers Formulation Research Articles

Nanostructured Lipid Carrier-Based Delivery of Pioglitazone for Treatment of Type 2 Diabetes.

Pioglitazone (PGZ) is utilized as a therapeutic agent in the management of (type 2) diabetes to control blood glucose levels. The existing research work was intended to make and optimize PGZ-containing NLCs (nanostructured lipid carriers). The fabricated nanostructured lipid carrier preparation was optimized by using different concentrations of the surfactants (Tween 80 and Span 80) and solid lipid (Compritol® 888 ATO) and liquid lipid (Labrasol®) while keeping the concentration of drug (PGZ), and co-surfactants (poloxamer 188) the same. The optimized NLC formulation (PGZ-NLCs) was further assessed for physical and chemical characterization, in vitro PGZ release, and stability studies. The optimized PGZ-NLCs have shown an average diameter of 150.4 nm, EE of 92.53%, PDI value of 0.076, and zeta-potential of −29.1 mV, correspondingly. The DSC thermal analysis and XRD diffractograms had not presented the spectrum of PGZ, confirming the comprehensive encapsulation of PGZ in the lipid core. PGZ-NLCs showed significantly extended release (51% in 24 h) compared to the unformulated PGZ. Our study findings confirmed that PGZ-NLCs can be a promising drug delivery system for the treatment of type 2 diabetes.

Hypolipidemic Activity of Olive Oil-Based Nanostructured Lipid Carrier Containing Atorvastatin.

Currently, hyperlipidemia is a growing health issue that is considered a risk factor for obesity. Controlling body weight and modifying life style in most of cases are not adequate and the condition requires medical treatment. Statin drugs (mainly Atorvastatin (ATO)), have been used broadly and for long time as medications for handling higher levels of lipid, especially bad cholesterol, which accordingly controls the prevalence of obesity. Still, the obstacle that stands in front of any formulation is the poor solubility of the drug. Low solubility of ATO came up with poor absorption as well as poor bioavailability. This paved the way for the present study, which aimed to exploit nanotechnology and develop certain nanolipid carriers that could accommodate hydrophobic drugs, such as ATO. Nanostructured lipid carrier (NLC) containing ATO was fabricated using olive oil. Olive oil is natural plant oil possessing confirmed hypolipidemic activity that would help in improving the efficacy of the formulation. Via applying the Quality by Design (QbD) approach, one NLC formula was selected to be optimized based on appropriate size and higher entrapment. Optimized ATO-NLC was scrutinized for zeta potential, in vitro study and kinetic profile. Moreover, stability testing and in vivo hypolipidemic behavior was conducted. The optimized NLC formulation seemed to show particle size (254.23 nm) with neutral zeta potential (−1.77 mV) and entrapment efficiency (69.56%). The formulation could be prolonged for 12 h and provided higher % of release (97.17%). Stability testing confirmed the role of modifying the surface of the formulation with PEG-DSPE in providing a highly stable formulation that could withstand three months storage in two altered conditions. Ultimately, optimized ATO-NLC could successfully lower total cholesterol level in rats induced with obesity and fed a high-fat diet. Remarkably, ATO-NLC prepared with olive oil, in addition to shielding its surface, would provide a stable formulation that holds up the synergistic action between olive oil and ATO.

Hyaluronic acid coated teriflunomide (A771726) loaded lipid carriers for the oral management of rheumatoid arthritis

Systemic rheumatoid arthritis treatment has been associated with numerous side effects. We attempted to formulate hyaluronic acid (HA)-coated teriflunomide (TER)-loaded nanostructured lipid carriers (NLCs) that can target inflamed rheumatic joints following oral administration. In vitro evaluation including colloidal characteristics, drug release and stability studies were conducted. Also, cytotoxicity studies on THP1 and peripheral blood mononuclear cells besides testing the binding of HA coated TER-NLCs to CD44 receptors were carried out. Furthermore, pharmacokinetics following oral administration, anti-arthritic effects, hepato and nephrotoxicity of NLCs were assessed.Selected NLCs formulation was approximately 284.9 ± 3.8 nm in size with 96.89 ± 0.45% entrapment efficiency and provided a sustained release for 30 days. NLCs showed good stability that was confirmed by TEM examination. Cell culture studies revealed that HA-coated TER- NLCs showed superior cytotoxicity and binding affinity to CD44 receptors compared with TER suspension. In vivo studies demonstrated the superiority of NLCs in increasing TER bioavailability, reducing TNF-α serum levels and improving joint healing that was evidenced in both histopathological and X-ray radiographic examination. This may be attributed to the ability of HA-coated TER-NLCs to target rheumatic joints passively and actively by targeting CD44 receptors that are overexpressed in rheumatic joints.

Nanoformulations with synthetic and plant-derived compounds for cattle tick control

Nanocarriers of acaricidal compounds improve the bioavailability, absorption, and tissue distribution of active ingredients, releasing them in a slow, targeted way and protecting them against premature degradation. Thus, this study aimed to develop formulations from solid lipid nanoparticles (SLN), or nanostructured lipid carriers (NLC) associated with cypermethrin (cip) + chlorpyrifos (chlo) and vegetable compounds (citral, menthol, or limonene). Particles were then characterised, and their efficacy was verified on R. microplus in comparison to nanoformulations without the plant-based compounds. Six different formulations were developed and characterised by dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Formulations 1 (SLN+cyp+chlo+citral), 2 (SLN+cyp+chlo+menthol), 3 (SLN+cyp+chlo+limonene), 4 (NLC+cyp+chlo+citral), 5 (NLC+cyp+chlo+menthol) and 6 (NLC+cyp+chlo+limonene) had mean diameters from 286 to 304 nm; polydispersion from 0.16 to 0.18; zeta potential from –15.8 to −20 mV, concentration from 3.37 ± 0.24 × 1013 to 5.44 ± 0.18 × 1013 particles/mL and encapsulation efficiency (EE) > 98.01 % for all active ingredients. All formulations were evaluated for their acaricidal potential by the larval packet test (LPT) and compared with nanoformulations without the plant-based compounds. Formulations were also compared with positive (Colosso® at 512 µg/mL) and negative controls (distilled water and nanoparticles without active ingredients). The SLN (1, 2 and 3) and NLC (4, 5 and 6) formulations, at 7 µg/mL, resulted in 90.4 % , 75.9 % , 93.8 % , 100 % , 95.1 % and 72.7 % mortality. The data demonstrated that the addition of citral, menthol or limonene in the formulations improved their acaricide action against tick larvae. Except for formulation 4, for which it was not possible to determine lethal concentrations (LC). Formulations, 1, 2, 3, 5 and 6 reached LC50 and LC90 values of 3.3 and 7.2, 5.4 and 9.2, 4.0 and 8.1, 2.3 and 5.4 as well as 5.5 and 9.4 µg/mL, respectively. It was possible to encapsulate the active ingredients and characterise the lipid carrier systems. SLN and NLC protected the active ingredients against degradation in solution and increased the overall stability. A stabile solution is necessary for synthesizing commercial acaricidal products. It is hoped that these findings may contribute to new studies focused on the use of nanocarriers in tick formulations. By reducing the amount or concentration of active ingredients within commercial products, the risk of residues presents in food of animal origin or remaining in the environment is reduced. Nanocarriers help prevent these challenges, while still maintaining effective parasitic control. Utilizing a combination of natural and synthetic products can be part of integrated management solutions and can help overcome widespread acaricide resistance in populations of cattle ticks.

Design of Besifloxacin HCl-Loaded Nanostructured Lipid Carriers: In Vitro and Ex Vivo Evaluation.

Objective: In the treatment of severe cases of bacterial keratitis, conventional eye drops containing antibiotics should be applied daily and very frequently. The aim of this study is to develop low-dose high-effect formulations with the prepared nanostructured lipid carrier (NLC) formulations to reduce antibiotic resistance and increase patient compliance. Methods: NLC formulations were loaded with besifloxacin HCl (BHL) and the besifloxacin HCl: sulfobutyl ether beta-cyclodextrin (SBE-CD) complex. Positive charge was gained with chitosan, and corneal permeation and resolubility were increased with SBE-CD. In vitro characterization studies, permeability studies, and cytotoxicity and ex vivo transport studies were carried out. Results: In this study, it was found that SBE-CD increased BHL's solubility by 8-fold based on phase solubility studies. The optimized NLCs were small in size (13.63-16.09 nm) with a low polydispersity index (0.107-0.181) and adequate BHL drug loading efficiency. In vitro release studies showed that formulations were released approximately for 8 h and at levels over the minimum inhibitory concentration of Pseudomonas aeruginosa and Staphylococcus aureus. NLC formulations had a better corneal permeation rate than the marketed product during 6 h of ex vivo studies. Conclusions: According to in vitro and ex vivo data, it was determined that the most favorable NLC formulation was the formulation containing BHL/SBE-CD that was covered with chitosan. It has the highest drug loading capacity and one of the highest ex vivo corneal passage levels, along with desired drug release. The formulation containing BHL/SBE-CD and chitosan can be a potential alternative for the treatment of bacterial keratitis.

Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties.

A series of novel Schiff bases-based TMP moieties have been designed and synthesized as potential anticancer agents. The target Schiff bases were screened for their cytotoxic activity against the MDA-MB-231 breast cancer cell line. Most of the tested molecules revealed good cytotoxic activity, especially compounds 4h, 4j and 5d. Being the most potent, compound 4h showed good tubulin polymerization inhibition activity as revealed by immunofluorescence analysis and ELISA assay. Additionally, compound 4h was screened for cell cycle disturbance and apoptosis induction. Pre-G1 apoptosis and cell growth halt at the G2/M phase were discovered to be caused by it. Moreover, compound 4h induced apoptosis via p53 and Bax activation, as well as reduced the level of Bcl-2. Additionally, the most potent compound 4h was lodged on nanostructured lipid carriers (NLCs). 23 full factorial design was involved to govern the influence of the fabrication variables on the in vitro characters of the casted NLCs. F3 was picked as the optimum formula exhibiting dominant desirability value 0.805, EE% 95.6 ± 2.4, PS 222.4 ±18.7, PDI 0.23 ± 0.05 and ZP −39.2 ± 3.9 Mv. Furthermore, F3 affirmed improved solubility and release over the drug suspension. In the comparative cytotoxic activity, F3 was capable of diminishing the IC50 by around 2.15 times for pure 4h, while nearly close to the IC50 of the reference drug. Thus, NLCs could be a potential platform for boosted antitumor activity.

Development of lipid nanoparticles for transdermal loteprednol etabonate delivery

Aim Loteprednol etabonate (LE) is a new generation corticosteroid that is used for the treatment of inflammatory and allergic conditions of the eye. Therefore, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were attempted to improve transdermal LE delivery for the first time. Methods SLN and NLC were produced by hot homogenisation and ultrasonication technique. Their physical stability was monitored for 3 months of storage. Drug release and permeation of SLN and NLC through the porcine skin were investigated. Results It was determined that SLN and NLC mean particle size of 139.1 nm had a homogeneous particle size distribution (∼0.169 PI) and the mean charge was −23.6. They were found to be stable both physically and chemically at room temperature. Conclusion SLN and NLC formulations of LE can be stated among the systems that can be an alternative to conventional systems with fewer side-effects in the treatment of inflammatory problems.

Physicochemical Characteristics, Stability, and Irritability of Nanostructured Lipid Carrier System Stabilized with Different Surfactant Ratios

Background: One of the vital variables affecting the stability and the characteristics of the Nanostructured Lipid Carrier (NLC) is the surfactant concentration. Using the two combinations of surfactants can cause higher stability and a better characteristic of NLC. Tween 80 and Span 20 are anionic surfactants whose combination has not been studied for use in NLC systems. Objective: Determine the effect of different surfactant ratios of Tween 80 and Span 20 on the physicochemical characteristics, stability, and irritability of NLC using the High Shear Homogenization (HSH) method. Methods: Four different surfactant ratios were used in the NLC formulation, in which the ratio of Tween 80:Span 20 were 5:5, 6:6, 7:7, and 8:8, respectively. In this NLC system, cetyl palmitate served as solid lipid, medium-chain triglyceride (CrodamolTM) as liquid lipid, Tween 80, and Span 20 as surfactant components. NLC was characterized for organoleptic, viscosity, pH, zeta potential, particle morphology, particle size, and polydispersity index (PDI), then evaluated for stability using the real-time and freeze-thaw method, and irritability effect. Results: The different ratios of Tween 80 and Span 20 had no significant effect on the particle size, PI, and irritation score of the NLC system. On the other hand, it influenced all formulas' pH value, viscosity, zeta potential, and stability. Conclusions: The different ratios of surfactant combination affect the characteristics and stability of the NLC system.

Co-administration of tariquidar using functionalized nanostructured lipid carriers overcomes resistance to docetaxel in multidrug resistant MCF7/ADR cells

To overcome multidrug resistance (MDR) and to enhance the efficacy of docetaxel (DTX), tariquidar (TRQ) was co-administered with DTX using nanostructured lipid carriers (NLC) functionalized with polyethylene glycol (PEG) and RIPL peptide (P/R). DTX- and TRQ-loaded plain NLC and P/R-NLC (P/R–N) were prepared using the solvent emulsification evaporation technique. All NLC samples showed a homogeneous spherical morphology and nano-sized dispersion (<210 nm) (zeta potential, −19 to −6 mV). DTX or TRQ was successfully encapsulated in NLC formulations (encapsulation efficiency >95%; drug loading 73–90 μg/mg). All NLC formulations were stable for 4 weeks when stored at 4 °C. Drug release was diffusion-controlled. DTX/TRQ combination at a 1:1 w/w ratio showed the highest synergism with a combination index value of 0.285 and was selected as the optimum combination. TRQ-P/R–N significantly enhanced the intracellular accumulation of Rhodamine 123 in MCF7/ADR cells. The co-administration of drug-loaded P/R-Ns led to potent and dose-dependent cytotoxicity and high MDR reversal efficiency. Co-treatment with DTX-P/R–N and TRQ-P/R–N increased apoptosis and enhanced G2/M cell cycle phase distribution in MCF7/ADR cells. These results indicate that the co-administration of DTX and TRQ using P/R-Ns may be a promising strategy to overcome MDR by P-gp inhibition in tumor treatments.

Nanostructured Lipid Carriers System Solid Lipid Poloxamer and Stearic Acid with Liquid Lipid Soybean Oil

Nanostructured Lipid Carriers (NLC) are lipid-based carrier system that use a matrix combination in the form of solid and liquid which are stabilized with the addition of surfactant. This NLC was developed to facilitate the dispersion of hydrophobic bioactive compound in a hydrophilic system. This research aims to get the right formulation and can develop stable characterization, using solid lipids Poloxamer and Stearic Acid with liquid lipids Soybeans Oil using surfactant Tween 80 and co-surfactant Propyleneglycol.. The to make the formulation of NLC with a ratio of poloxamer and stearic acid as solid lipid: soybeans oil asliquid lipid is 3:3, 4:2, 5:1 ,surfactant tween 80 and co surfactant propyleneglycol. Test the NLC characterization including PH value, viscosity, particle size, and polydispersity index. Data analysis used to evaluate the characteristics of the obtained NLC using descriptive. The result of the research showed that NLC had good characteistics at a solid lipid poloxamer and stearic acid with Soybean oil liquid lipid ,pH in the range 4-6; good viscosity; good particles have a range of 1000nm; and polydispersity index which shows the results of monodispersion. Nanostructured Llipid Carriers with solid lipid poloxamer and stearic acid and liquid lipid soybean oil obtained good characteristics.

Development of topical gel containing Capsicum oleoresin encapsulated Tamanu nanocarrier and its analgesic and anti-inflammatory activities

Capsicum oleoresin (CO), which consists capsaicin as the most effective component, has been used as a topical treatment of neuropathic pain. However, topical formulations with adequate concentrations of capsaicin, which are required to achieve effective pain relief, cause several local adverse skin reactions such as burning sensation, itching, skin redness, and pain. Tamanu oil (TO), a fatty oil containing both liquid lipids and solid lipids derived from Calophyllum inophyllum seeds, has emerged as a potential ingredient for the preparation of a nanostructured lipid carrier (NLC)-based gel formulation in order to reduce the local adverse skin reactions as well as enhance the analgesic effect of capsaicin topical. In this study, Tamanu oil-based NLC encapsulating Capsicum oleoresin (CO@TO) Gel was prepared using emulsification followed by homogenization methods. The results suggested the best formulation of the CO@TO was prepared from 20% Tamanu oil, 12% tween 80, 1% lecithin and 1.5% Capsicum oleoresin with homogenization at 20,000 rpm for 10 min. The CO@TO particles was sphere and unique with diameter of ~147 nm and zeta potential of − 76 mV. The capsaicin EE and LC of the CO@TO was ~99% and 0.15%, respectively. The CO@TO performed sustainable capsaicin release during 48 h, which fitted with Korsmeyer-Peppas kinetic model. The skin irritation test on rabbits demonstrated that the CO@TO Gel bearing 0.1% capsaicin caused no skin irritation. Meanwhile in vivo studies on mice illustrated that the CO@TO Gel performed similar analgesic and anti-inflammation effects as the commercial drugs Paracetamol/Codeine and diclofenac, respectively. The CO@TO Gel in this study would be a potential Tamanu oil-based nanostructured lipid carrier formulations for capsaicin topical products.

Nanostructured lipid carrier-embedded polyacrylic acid transdermal patches for improved transdermal delivery of capsaicin

Capsaicin has been used as a topical treatment for skeletomuscular and neuropathic pain. However, it has some side effects when it is applied to the skin such as burning, erythema, and skin irritation resulting in poor patient compliance. These adverse effects are caused by the rapid penetration of capsaicin into the outer layer of the epidermis and low permeation to the dermis layer. This study aimed to develop nanostructured lipid carriers (NLCs) embedded transdermal patches for improved transdermal delivery of capsaicin. An optimum formulation of NLCs (0.3% capsaicin) with a particulate size smaller than 200 nm, narrow size distribution, and acceptable colloidal stability was used for preparing transdermal patches. Polyacrylic acid (7%) was employed as the polymer base of the transdermal patches as it provided high adhesive performance and a sustained release of capsaicin. Moreover, the patches containing capsaicin-loaded NLCs could offer a higher deposition of capsaicin in the deeper layer of the skin compared to the conventional capsaicin patches. In vivo skin irritation studies indicated that the conventional capsaicin patches can cause skin irritation and redness, whereas capsaicin NLCs-loaded patches exhibited lower skin side effects. Therefore, the capsaicin NLCs-loaded patches could be a potential delivery system of capsaicin through the skin with possibly reduced skin irritation.

Hybrid Nanobeads for Oral Indomethacin Delivery.

The oral administration of the anti-inflammatory indomethacin (INDO) causes severe gastrointestinal side effects, which are intensified in chronic inflammatory conditions when a continuous treatment is mandatory. The development of hybrid delivery systems associates the benefits of different (nano) carriers in a single system, designed to improve the efficacy and/or minimize the toxicity of drugs. This work describes the preparation of hybrid nanobeads composed of nanostructured lipid carriers (NLC) loading INDO (2%; w/v) and chitosan, coated by xanthan. NLC formulations were monitored in a long-term stability study (25 °C). After one year, they showed suitable physicochemical properties (size < 250 nm, polydispersity < 0.2, zeta potential of −30 mV and spherical morphology) and an INDO encapsulation efficiency of 99%. The hybrid (lipid-biopolymers) nanobeads exhibited excellent compatibility between the biomaterials, as revealed by structural and thermodynamic properties, monodisperse size distribution, desirable in vitro water uptake and prolonged in vitro INDO release (26 h). The in vivo safety of hybrid nanobeads was confirmed by the chicken embryo (CE) toxicity test, considering the embryos viability, weights of CE and annexes and changes in the biochemical markers. The results point out a safe gastro-resistant pharmaceutical form for further efficacy assays.

Development of heat-stable gelatin-coated nanostructured lipid carriers (NLC): Colloidal and stability properties

Heat stable vitamin D3 loaded nanostructured lipid carriers (NLCs) were developed by edible solid lipids with high melting points (beeswax and margarine) and alpha-tocopherol as liquid oil. These NLCs were coated by gelatin to be spray dried and easily portable. The effect of solid lipid type (beeswax or margarine), solid-to-liquid lipid ratio, and surfactant composition (Tween-80/polyglycerol ester) on mean particle size, polydispersity index (PDI), and encapsulation efficiency (EE) of NLCs were studied. Results showed that the beeswax-based NLC had higher mean size and EE (%) than the margarine-based ones. The morphology and polymorphic structures of selected formulations of NLCs were studied and compared with their solid lipid nanoparticles (SLNs). Gelatin was used for coating NLC particles during spray drying of NLC suspensions. Vitamin D3 was stable in both beeswax and margarine-based NLCs during two months' storage at ambient temperature. However, the stability of vitamin D3 in the beeswax-based NLCs was higher than in margarine-based ones during cooking and frying of oil.

Nanostructured lipid carrier for transdermal gliclazide delivery: development and optimization by Box-Behnken design

The aim of current study was to prepare and optimize the nanostructured lipid carrier (NLC) for transdermal gliclazide (GCZ) delivery. The melt emulsification followed by ultrasonication technique was utilized to prepare GCZ–loaded-NLC. The optimization of NLC was achieved by Box-Behnken design. The surfactant (Tween 20) % (X1), total lipid (glyceryl monostearate + Lauroglycol™ 90) % (X2), and sonication time (min) (X3) were chosen as independent variables, while particles size (Y1), polydispersity index (Y2), and entrapment efficiency (Y3) were selected as response. Further, the prepared NLC was estimated for in vitro drug release study, ex vivo skin permeation and confocal laser scanning microscopy (CLSM) studies. Results of present study demonstrated that the optimized GCZ loaded NLC formulation presented the particles size, polydispersity index, zeta potential, and entrapment efficiency of 120.4 nm, 0.316, −5.58 mV, and 87.32% respectively. The in vitro drug release study indicated drug release of 68.27 ± 2.98% and 45.87 ± 2.85% for GCZ-NLC and conventional GCZ dispersion respectively. The GCZ-NLC-Gel formulation exhibited transdermal drug permeation of 76.89 ± 2.52% as compared to conventional gel (45.65 ± 2.79%). The CLSM of rat skin treated with NLC gel exhibited a deeper permeation (35 μm) in comparison to the conventional gel (15 μm). In conclusion, GCZ loaded NLC was successfully optimized using Box-Behnken design that contributed many advantages over conventional formulation and thus demonstrating NLC as propitious carriers for the transdermal GCZ delivery.

Development and validation of a reversed-phase HPLC method for quantification of 1’-acetoxychavicol acetate content in a nanostructured lipid carrier formulation

Development and validation of a reversed-phase HPLC method for quantification of 1’-acetoxychavicol acetate content in a nanostructured lipid carrier formulation

Optimization and Evaluation of Ketoconazole Loaded Nanostructured Lipid Carriers Employing Microwave-Assisted Technique

The present research work is designed to formulate, optimize and evaluate the ketoconazole loaded nanostructured lipid carriers for the topical delivery. Ketoconazole loaded nanostructured lipid carriers were prepared by one pot single-step microwave assisted technique using Compritol® 888 ATO, Labrafac PG and soya lecithin employing 2-factors 3-level experimental design. The p-size of the optimized batch of microwave assisted ketoconazole loaded nanostructured lipid carriers was found to be 60.15 nm. The in vitro drug release in 24 h study showed the biphasic release pattern, initial burst release for 5 h followed by slower release upto 24 h. Furthermore, ex vivo skin permeation study revealed that 3670.99 μg/cm2 and 4644.78 μg/cm2 of drug permeated from ketoconazole loaded nanostructured lipid carriers hydrogel and marketed formulation with the flux rate of 305.91 μg/cm2/h and 387.06 μg/cm2/h, respectively at the end of 24 h. Confocal laser scanning microscope images demonstrated appreciable cell uptake of 5(6)-Carboxyfluorescein loaded nanostructured lipid carriers hydrogel compared to 5(6)-Carboxyfluorescein-loaded plain hydrogel. Optimized batch of nanostructured lipid carrier formulation produced by microwave assisted technique produced particles in nm range with narrow polydispersity index and high entrapment efficiency. X-ray study confirmed that the crystalline nature of ketoconazole changed to amorphous form in the process of nanostructured lipid carrier formulation and thermal behavior analyzed by differential scanning calorimetry confirmed inclusion of drug into lipid matrix in its amorphous form. After performing the optimization and evaluations of nanostructured lipid carriers it can be concluded that nanostructured lipid carriers bear the potential to be explored further for the topical and other pharmaceutical applications.

Fabrication and characterization of nanostructured lipid carrier system for effective delivery of poorly water-soluble drug quetiapine fumarate

The aim of present study is to investigate the potential of nanostructured lipid carriers (NLCs) in improving the oral bioavailability of quetiapine fumarate, a second-generation antipsychotic drug. Quetiapine Fumarate (QF) loaded NLC were prepared by hot homogenization followed by an ultrasonication method. Response surface methodology - central composite design (CCD) was used to systemically examine the influence of concentration of capmul MCM EP, concentration of poloxamer 188 and concentration of egg lecithin on particle size (PS) and % entrapment efficiency (% EE) and to optimize the NLC formulation. The CCD consists of three factored design with five levels, plus and minus alpha (axial points), plus and minus 1 (factorial points) and the centre point. A mathematical relationship between variables was created by using Design Expert software Version 12. The statistical evaluations revealed that three independent variables were the important factors that affected the PS and % EE of QF loaded NLC. The best fitted mathematical model was linear and quadratic for PS and % EE respectively. The optimized formulations found with 218.1±0.14nm of PS and 93±0.16% of % EE. Results illustrated the superiority of developed QF loaded NLC formulation as a stable drug delivery system, providing better bioavailability with the possibility of better treatment for psychological disorders.

A green chemistry approach towards synthesizing hydrogel for sustained ocular delivery of brinzolamide: In vitro and ex vivo evaluation

Brinzolamide is a carbonic anhydrase inhibitor used in the eye drop form for the treatment of glaucoma. It requires frequent dosing to attain therapeutic concentration. Therefore, this study aimed to prepare sustained ocular drug delivery of brinzolamide. The objective of the study was to prepare a hydrogel loaded with a nanostructured lipid carrier (NLC) of brinzolamide. The hydrogel was prepared by a green synthesis approach using genipin as a natural crosslinking agent and polymers such as carboxymethyl chitosan and poloxamer 407. The melt emulsification-ultra sonication method was used to prepare a nanostructured lipid carrier of brinzolamide, which was loaded into a hydrogel using a swelling and loading method. The NLC formulation has shown small particle sizes of 111.20 ​± ​2.15 ​nm, polydispersity index of 0.280 ​± ​0.005 and % entrapment efficiency of 82.16% ​± ​0.14%. The NLC-loaded hydrogels of brinzolamide formulations were studied for swelling properties and showed temperature and pH-responsive swelling behavior. The optimized hydrogel formulation has been studied for in vitro drug release and showed drug release for a longer duration (24 ​h) than marketed eye drops (8 ​h). In an ex vivo study, hydrogel formulations showed transcorneal permeability 4.54 times greater than marketed eye drops. The hydrogel formulation of brinzolamide produced by the green synthesis method has shown sustained-release properties with no sign of ocular irritation. Hence, the hydrogel of brinzolamide-loaded NLC would be the potential drug delivery approach in the near future for sustained ocular drug delivery in glaucoma management.

Combined delivery of TLR2 and TLR7 agonists by Nanostructured lipid carriers induces potent vaccine adjuvant activity in mice

Toll-like receptor (TLR) agonists are promising adjuvants and the combination of TLR agonists enhance immune responses by providing synergistic immune activity via triggering different signalling pathways. However, systematic cytotoxicity due to the immediate release of such immune potentiators from the site of injection hampers its clinical performance. Nanostructured lipid carriers (NLCs) offer a possibility to incorporate multiple TLR agonists with high encapsulation efficiency and slow drug release. Herein, we synthesized NLCs from didodecyldimethylammonium bromide (D12DAB) and oleic acid and used these to co-encapsulate a Pam2CS derivative (T-2, TLR2 agonist) with an imidazoquinoline derivative (T-7, TLR7 agonist) as a combination vaccine adjuvant. Hydrodynamic diameter and zeta potential of the prepared NLCs were found to be in the range of 200–500 nm and 23–27 mV, respectively. Spherical shape and size of prepared NLCs were also assessed through Field Emission Scanning Electron Microscopy (FE-SEM) and Transmission Electron Microscopy (TEM) analysis. In-vitro release studies of T-7 demonstrated sustained release and the addition of lipopeptide T-2 augmented encapsulation efficiency (from 84 to 92.9%) with a slight trigger in the release percentage. All NLC formulations were screened in TLR2/1, TLR2/6, TLR7 and TLR8 reporter cell lines and loaded NLC formulation showed high TLR2 and TLR7 agonistic activity. Adjuvant potency was evaluated through intramuscular immunization of female C57BL/6 mice with recombinant hepatitis B surface antigen and influenza hemagglutinin protein. T-2 and T-7 loaded NLCs induced good protective efficacy in mice challenged with a lethal dose of influenza virus.