Nanostructured Lipid Carriers Formulation Research Articles

Double Optimization of Rivastigmine-Loaded Nanostructured Lipid Carriers (NLC) for Nose-to-Brain Delivery Using the Quality by Design (QbD) Approach: Formulation Variables and Instrumental Parameters.

Rivastigmine is a drug commonly used in the management of Alzheimer’s disease that shows bioavailability problems. To overcome this, the use of nanosystems, such as nanostructured lipid carriers (NLC), administered through alternative routes seems promising. In this work, we performed a double optimization of a rivastigmine-loaded NLC formulation for direct drug delivery from the nose to the brain using the quality by design (QbD) approach, whereby the quality target product profile (QTPP) was the requisite for nose to brain delivery. The experiments started with the optimization of the formulation variables (or critical material attributes—CMAs) using a central composite design. The rivastigmine-loaded NLC formulations with the best critical quality attributes (CQAs) of particle size, polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) were selected for the second optimization, which was related to the production methods (ultrasound technique and high-pressure homogenization). The most suitable instrumental parameters for the production of NLC were analyzed through a Box–Behnken design, with the same CQAs being evaluated for the first optimization. For the second part of the optimization studies, were selected two rivastigmine-loaded NLC formulations: one produced by ultrasound technique and the other by the high-pressure homogenization (HPH) method. Afterwards, the pH and osmolarity of these formulations were adjusted to the physiological nasal mucosa values and in vitro drug release studies were performed. The results of the first part of the optimization showed that the most adequate ratios of lipids and surfactants were 7.49:1.94 and 4.5:0.5 (%, w/w), respectively. From the second part of the optimization, the results for the particle size, PDI, ZP, and EE of the rivastigmine-loaded NLC formulations produced by ultrasound technique and HPH method were, respectively, 114.0 ± 1.9 nm and 109.0 ± 0.9 nm; 0.221 ± 0.003 and 0.196 ± 0.007; −30.6 ± 0.3 mV and −30.5 ± 0.3 mV; 97.0 ± 0.5% and 97.2 ± 0.3%. Herein, the HPH was selected as the most suitable production method, although the ultrasound technique has also shown effectiveness. In addition, no significant changes in CQAs were observed after 90 days of storage of the formulations at different temperatures. In vitro studies showed that the release of rivastigmine followed a non-Fickian mechanism, with an initial fast drug release followed by a prolonged release over 48 h. This study has optimized a rivastigmine-loaded NLC formulation produced by the HPH method for nose-to-brain delivery of rivastigmine. The next step is for in vitro and in vivo experiments to demonstrate preclinical efficacy and safety. QbD was demonstrated to be a useful approach for the optimization of NLC formulations for which specific physicochemical requisites can be identified.

Nose-to-brain delivery of sumatriptan-loaded nanostructured lipid carriers: preparation, optimization, characterization and pharmacokinetic evaluation.

Migraine is a neurological disorder with unilateral pulsatile headache which can affect the functions of sufferers. Migraineurs experience some undesirable symptoms such as pain, nausea, vomiting and in some cases auras which make the oral delivery non-selective. The lipid nanoparticles are considered as good carriers for nose-to-brain drug delivery. The present study aimed to formulate and evaluate a sumatriptan-loaded nanostructured lipid carrier (NLC). A drug-loaded NLC was optimized using D-optimal design of experiment and then the characterization of the formulated NLC including particle size, zeta potential, electron microscopy, thermal analysis, drug loading efficiency and release kinetics were carried out. Pharmacokinetic evaluations were also performed during an in-vivo study on Sprague-Dawley rats and neuropharmacokinetic parameters such as drug targeting efficiency (DTE) and direct transport percentage (DTP) were calculated. The optimization of experiments led to nanoparticles with 101nm mean diameter and polydispersity index (PDI) of 0.27. The drug entrapment efficiency (EE) for optimized nanoparticle was found to be 91.00%. DTE and DTP of intranasal-administered NLC were calculated 258.02% and 61.23%, respectively. Neuropharmacokinetic evaluation of intranasal NLC dispersion represents a suitable brain delivery system. The DTP of NLC formulation suggests the desirable entrance of sumatriptan into the brain.

Conjugated linoleic acid loaded nanostructured lipid carrier as a potential antioxidant nanocarrier for food applications.

The encapsulation of fatty acids in nanocarrier systems is a very effective technique in improving their biological efficiency and controlled delivery. Nanostructured lipid carrier (NLC) is a major type of lipid‐based nanoparticle. This study is focused on producing nanolipid carrier containing conjugated linoleic acid and fortifying low‐fat milk using this nanoparticle. Nanostructured lipid carriers were produced by hot high‐shear homogenization containing 1.5% Poloxamer 407, cocoa butter as solid lipid, and conjugated linoleic acid as liquid oil in ratio of 10:1. Results showed that the nanoparticles sized 81 nm with monomodular dispersity and the system was stable at 4 and 22°C for 40 days. Zeta potential and encapsulation efficiency (%EE) were −15.8 mV and 98.2%, respectively. Scanning electron microscopy (SEM) showed that the particles are in spiral form and small size and no significant aggregation was observed because of few changes in the system turbidity after storage time. The result of oxidative stability showed that using Nanostructured lipid carriers system resulted in lower malone dialdehyde production. Conjugated linoleic acid was protected at level of 3.9% of milk fatty acids in Nanostructured lipid carrier formulation during storage time. Based on these findings, Nanostructured lipid carriers system is an appropriate and stable nanocarrier system for delivery of nutraceuticals in foods and can be used in protecting them against oxidation, heating, and other processes in order to fortify foods and beverages.

Oral Bioavailability Enhancement of Raloxifene with Nanostructured Lipid Carriers.

Raloxifene hydrochloride (RLX) shows poor bioavailability (<2%), high inter-patient variability and extensive gut metabolism (>90%). The objective of this study was to develop nanostructured lipid carriers (NLCs) for RLX to enhance its bioavailability. The NLC formulations were produced with glyceryl tribehenate and oleic acid. The particle characteristics, entrapment efficiency (EE), differential scanning calorimetry (DSC), in vitro drug release, oral bioavailability (in rats) and stability studies were performed. The optimized nanoparticles were 120 ± 3 nm in size with positive zeta potential (14.4 ± 0.5 mV); % EE was over 90% with the drug loading of 5%. The RLX exists in an amorphous form in the lipid matrix. The optimized RLX-NLC formulation showed sustained release in vitro. The RLX-NLC significantly (p < 0.05) enhanced oral bioavailability 3.19-fold as compared to RLX-free suspension in female Wistar rats. The RLX-NLC can potentially enhance the oral bioavailability of RLX. It can also improve the storage stability.

Improved anti-arthritic activity of ginger extract, a traditional medicine, using novel drug delivery approach.

Ginger and castor oil, both are used in traditional medicine to treat arthritis, the latter is also commonly used as a vehicle in these systems of medicine. The study was designed to prepare a nanostructured lipid carrier (NLC) of ginger extract using castor oil as a novel liquid lipid and evaluate its safety and efficacy in rheumatoid arthritis in experimental animals. Ginger extract was standardized using High performance liquid chromatography (HPLC). The optimized NLC formulation was characterized and its therapeutic efficacy was evaluated in Chronic Freund's adjuvant (CFA) induced arthritis in experimental animals. Ginger extract contained 38.76±3.01%w/w of 6-gingerol. The optimized NLC formulation showed a particle size of around 205nm, a zeta potential of-33.7 and %entrapment efficiency of 76.59±0.83%. Reduction in primary inflammation was significantly higher with NLC when compared with ginger extract and castor oil alone (p<0.001). The formulation also improved hyperalgesia in rats. Castor oil can be used as a novel lipid in the preparation of NLC. The NLC effectively enhanced the therapeutic value of poorly bioavailable ginger extract.

Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study.

The opposing effect of the blood–brain barrier against the delivery of most drugs warrants the need for an efficient brain targeted drug delivery system for the successful management of neurological disorders. Temazepam-loaded nanostructured lipid carriers (NLCs) have shown possibilities for enhancing bioavailability and brain targeting affinity after oral administration. This study aimed to investigate these properties for insomnia treatment. Temazepam-NLCs were prepared by the solvent injection method and optimized using a 42 full factorial design. The optimum formulation (NLC-1) consisted of; Compritol® 888 ATO (75 mg), oleic acid (25 mg), and Poloxamer® 407 (0.3 g), with an entrapment efficiency of 75.2 ± 0.1%. The average size, zeta potential, and polydispersity index were determined to be 306.6 ± 49.6 nm, −10.2 ± 0.3 mV, and 0.09 ± 0.10, respectively. Moreover, an in vitro release study showed that the optimized temazepam NLC-1 formulation had a sustained release profile. Scintigraphy images showed evident improvement in brain uptake for the oral 99mTc-temazepam NLC-1 formulation versus the 99mTc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of 99mTc-temazepam NLC-1 formulation (292.7%), compared to that of oral 99mTc-temazepam suspension. Besides, the NLC formulation exhibited a distinct targeting affinity to rat brain. In conclusion, our results indicate that the developed temazepam NLC formulation can be considered as a potential nanocarrier for brain-mediated drug delivery in the out-patient management of insomnia.

Development of folic acid–loaded nanostructured lipid carriers for topical delivery: preparation, characterisation and ex vivo investigation

The present work is designed to achieve efficient localised skin delivery of folic acid (FA)–loaded nanostructured lipid carriers (NLCs) to infer efficient treatment of skin photoageing conditions induced via excessive exposure to ultraviolet (UV) radiation. FA NLCs were prepared by high-speed homogenisation followed by ultrasonication. The obtained NLCs revealed high encapsulation efficiencies (89.42–99.26%) with nanometric particle sizes (27.06–85.36 nm) of monodisperse distribution (PDI = 0.137–0.442), zeta potential values >|27| mV, pseudoplastic rheological behaviour, good spreadability (2.25–3.30 cm) and promoted occlusive properties throughout 48 h. Optimised NLC formulations appeared as sphere-shaped particles using transmission electron microscopy, showed improved photostability of FA and prolonged in vitro release profile best fitted to Higuchi diffusion model. Ex vivo permeation and deposition of FA, employing Wistar rat skins, depicted enhanced permeability and existence of FA in skin layers after 6 h. Based on the obtained results, FA-loaded NLC formulations demonstrate a promising modality for anti-photoageing therapy.

Prevention of Type 1 Diabetes via a lipid Nanoparticle-Based Oral Immunotherapy that Targets Selective Lymphoid Tissues

Abstract Type 1 diabetes (T1D) is an untreatable autoimmune disease caused by the destruction of pancreatic beta cells by autoreactive T cells. Antigen presenting cells (APCs) malfunctions and aberrant accumulation of type 1 interferons contribute to T1D, and the inhibition of inflammatory cytokines signaling via JAK inhibitors like Tofacitinib (Tofa) has shown promise in the prevention of the disease. However, maintenance of a therapeutic concentration of these drugs is challenging and their prolonged use leads to significant side effects. Our objective was to design a controlled and localized delivery of Tofa via biocompatible lipid nanoparticles, Nanostructured Lipid Carrier (NLC), and assess if, via this strategy, a short-term administration would impact T1D development. We identified a formulation of NLC that had negligible toxicity, could be readily taken up by multiple immune cells, and had a favorable Tofa encapsulation efficiency. Live animal imaging confirmed these particles have the unique property of accumulating in lymphoid tissues, particularly in spleen, pancreatic and mesenteric lymph nodes when administrated via oral gavage. Ex-vivo, Tofa-NLC rapidly delivered Tofa to mouse APCs preventing their maturation and the release of inflammatory cytokines. Importantly, short-term administration of Tofa-NLC via oral gavage at early (3-week-old) or late (10-week-old) stage in disease prone NOD mice promoted a significant delay of T1D onset. Cell profiling and in vivo challenges indicated that this therapeutic effect is likely due to localized inhibition of APCs maturation and promotion of anergy in diabetogenic T cells. These results highlight the versatility of this lipid nanoparticle-based drug delivery strategy.

β-Sitosterol Loaded Nanostructured Lipid Carrier: Physical and Oxidative Stability, In Vitro Simulated Digestion and Hypocholesterolemic Activity.

The objective of the present study was to explore the potential of nanostructured lipid carriers (NLCs) for improving the oral delivery of β-sitosterol, a poorly water-soluble bioactive component with hypocholesterolemic activity. Two β-sitosterol formulations with different solid lipid compositions were prepared by melt emulsification, followed by the sonication technique, and the effect of storage conditions and simulated digestion on the physical, chemical and oxidative stability, bioaccessibility and release were extensively studied. Both NLC preparations remained relatively stable during the four weeks of storage at different conditions (4, 25 and 40 °C), with more superior stability at lower temperatures. The in vitro digestion experiment indicated a high physical stability after exposure to the simulated mouth and stomach stages and an improved overall β-sitosterol bioaccessibility at the end of the digestion. The NLCs presented an increased solubility and gradual release which could be justified by the remarkable affinity of β-sitosterol to the complex lipid mixture. An in vivo study demonstrated an improved reduction in the total cholesterol and low-density lipoprotein cholesterol plasma levels in mice compared with the drug suspension. These investigations evidenced the potential of the developed NLC formulations for the enhancement of solubility and in vivo performance of β-sitosterol.

Carvacrol loaded nanostructured lipid carriers as a promising parenteral formulation for leishmaniasis treatment

Leishmaniasis are a group of neglected infectious diseases caused by protozoa of the genus Leishmania with distinct presentations. The available leishmaniasis treatment options are either expensive and/or; cause adverse effects and some are ineffective for resistant Leishmania strains. Therefore, molecules derived from natural products as the monoterpene carvacrol, have attracted interest as promising anti-leishmania agents. However, the therapeutic use of carvacrol is limited due to its low aqueous solubility, rapid oxidation and volatilization. Thus, the development of nanostructured lipid carriers (NLCs) was proposed in the present study as a promising nanotechnology strategy to overcome these limitations and enable the use of carvacrol in leishmaniasis therapy. Carvacrol NLCs were obtained using a warm microemulsion method, and evaluated regarding the influence of lipid matrix and components concentration on the NLCs formation. NLCs were characterized by DSC and XRD as well. In addition, to the in vitro carvacrol release from NLCs, the in vitro cytotoxicity and leishmanicidal activity assays, and the in vivo pharmacokinetics evaluation of free and encapsulated carvacrol were performed. NLCs containing carvacrol were obtained successfully using a warm microemulsion dilution method. The NLCs formulation with the lowest particle size (98.42 ± 0.80 nm), narrowest size distribution (suitable for intravenous administration), and the highest encapsulation efficiency was produced by using beeswax as solid lipid (HLB=9) and 5% of lipids and surfactant. The in vitro release of carvacrol from NLCs was fitted to the Korsmeyer and Peppas, and Weibull models, demonstrating that the release mechanism is probably the Fickian diffusion type. Moreover, carvacrol encapsulation in NLCs provided a lower cytotoxicity in comparison to free carvacrol (p<0.05), increasing its in vitro leishmanicidal efficacy in the amastigote form. Finally, the in vivo pharmacokinetics of carvacrol after IV bolus administration suggests that this phenolic monoterpene undergoes enterohepatic circulation and therefore presented a long half-life (t1/2) and low clearance (Cl). In addition, C0, mean residence time (MRT) and Vdss of encapsulated carvacrol were higher than free carvacrol (p < 0.05), favoring a higher distribution of carvacrol in the target tissues. Thus, it is possible to conclude that the developed NLCs are a promising delivery system for leishmaniasis treatment.

Synergic pro-apoptotic effects of Ferulic Acid and nanostructured lipid carrier in glioblastoma cells assessed through molecular and Delayed Luminescence studies

Herein, we assessed the effect of Ferulic Acid (FA), a natural antioxidant with anti-cancer effect, on the human glioblastoma cells through molecular and Delayed Luminescence (DL) studies. DL, a phenomenon of ultra-week emission of optical photons, was used to monitor mitochondrial assessment. The effect of FA loaded in nanostructured lipid carriers (NLCs) was also assessed. To validate NLCs as a drug delivery system for glioblastoma treatment, particular attention was focused on their effect. We found that free FA induced a significant decrease in c-Myc and Bcl-2 expression levels accompanied by the apoptotic pathway activation. Blank NLCs, even if they did not induce cytotoxicity and caspase-3 cleavage, decreased Bcl-2, ERK1/2, c-Myc expression levels activating PARP-1 cleavage. The changes in DL intensity and kinetics highlighted a possible effect of nanoparticle matrix on mitochondria, through the involvement of the NADH pool and ROS production that, in turn, activates ERK1/2 pathways. All the effects on protein expression levels and on the activation of apoptotic pathway appeared more evident when the cells were exposed to FA loaded in NLCs. We demonstrated that the observed effects are due to a synergic pro-apoptotic influence exerted by FA, whose bio-availability increases in the glioblastoma cells, and NLCs formulation.

Moisturizing effects of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) using deionized and magnetized water by in vivo and in vitro methods.

Objective(s):The present study aimed to determine and compare moisturizing and occlusion effects of different solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) using magnetized water and deionized water.Materials and Methods:SLN formulations were prepared using various lipids, including Tripalmitin, Compritol®, Precirol®, and emulsifiers including Poloxamer and Tween 80. NLC formulations were also prepared with oleic acid and the same solid lipids. Two types of formulations were prepared; first with deionized water and then with magnetized water. Formulations were prepared using high shear homogenization and ultrasound methods. The products were analyzed by PSA (particle size analyzer), DSC (differential scanning calorimetry), and TEM (transmission electron microscopy). The moisturizing effect of formulations was determined by in vivo and in vitro methods. Results:Findings of the assessments demonstrated that in products prepared with magnetized water, 5% SLN Precirol® had the most moisturizing effect in vivo and 5% SLN Compritol® had the most moisturizing effect in vitro. The use of magnetized water in formulations can improve the effectiveness and increase the stability of moisturizing products.Conclusion:In this study, all products prepared with magnetized water showed more stability, smaller size, and more moisturizing effects compared with products prepared with deionized water.

Formulation and Characterization of Novel Nanostructured Lipid Carriers with Photoprotective Properties Made from Carnauba Wax, Beeswax, Pumpkin Seed Oil, and UV Filters

AbstractPumpkin seed oil (PSO) with carnauba wax and beeswax was used to develop nanostructured lipid carriers (NLC) loaded with a UV filter, Uvinul® A Plus B. The aims of the study were to optimize the concentration of PSO to develop a stable NLC formulation, determine storage stability of the NLC with and without PSO, and the synergistic effect of PSO‐NLC with UV filter for photoprotective properties. The physical properties of NLC were optimized based on the mean particle size, polydispersity index, and storage stability. The optimized NLC consisted 10% lipid phase (3.5% carnauba wax, 3.5% beeswax, and 3.0% PSO) and 90% aqueous phase. After optimization, Uvinul® A Plus B was added in the optimized PSO‐NLC to produce a photoprotective formulation. Uvinul® A Plus B consisted of both UVA (Diethylamino Hydroxybenzoyl Hexyl Benzoate) and UVB (Ethylhexyl Methoxycinnamate) filters. The NLC produced with PSO and Uvinul® A Plus B had mean particle size of 135 ± 2 nm and showed good physical stability under storage time. Besides that, the NLC produced also proven to have positive effect in enhancing the entrapment efficiency and drug loading, which were 82.86 ± 0.15% and 55.41 ± 0.04%, respectively, and showed sun protection factor value of 16.61 ± 3.45. The results indicated the presence of synergistic effect among the PSO‐NLC with Uvinul® A Plus B.

SCREENING STUDY FOR FORMULATION VARIABLES IN PREPARATION AND CHARACTERIZATION OF CANDESARTAN CILEXETIL LOADED NANOSTRUCTURED LIPID CARRIERS

The current study inspects the screening of the formulation components further, evaluates the physicochemical properties of the nanostructured lipid carriers (NLCs) for the antihypertensive drug as Candesartan Cilexetil (CC). The sequence screening of all excipients required for the preparation of NLCs should be performed. Firstly, the solubility of CC in different solid and liquid lipids is the major parameter for the selection of the best one. Precirol® ATO 5, Compritol ® 888 ATO and Glyceryl Monostearate (GMS) were showed the maximum solubility of the CC (1000±4.12 mg, 1500±4.15 mg and 1750±3.16 mg), respectively. Hence, they were selected as the solid lipids for the development of NLCs. Liquid lipids Transcutol® HP (30±2.21 mg/ml), Labrasol® ALF (25±1.32 mg/ml) and CapryolTM 90 (18±1.34 mg/ml) were observed to have good affinity for the drug on systematic screening of different liquid lipids. However, Precirol® ATO 5 was found to has good physical compatibility with Transcutol® HP, Compritol ATO 888 was found to has high physical miscibility with Labrasol® ALF and last GMS was appeared in good affinity and compatibly with CapryolTM 90. Hence, the following binary lipid mixtures (Precirol® ATO 5 - Labrasol® ALF), (Compritol® 888 ATO-Transcutol® HP) and (GMS - CapryolTM 90) were selected for the preparation of NLCs. The liquid–solid lipid mixture in the ratio up to 30:70 was observed to have sufficient melting point (55-59 0C). Lutrol F-68, Lutrol F-127, Cremophore EL and Cremophore® RH. In addition to, the combination of (Lutrol® F68:Cremophore® EL) and (Lutrol® F127: Cremophore® RH) were selected as the main surfactants for the preparation of NLCs formulations because of its good emulsification efficacy and homogeneity for the solid-liquid lipid mix. The prepared formulations were investigated for the different quality issues. All designed formulations observed in nanometer size of particles ranged from (408.9±11.5 to 114.6±8.3 nm) with high encapsulation efficiency around 99%. Also, the obtained results revealed that the ZP of the various formulations was consistently negative surface charge in between ((-13 ±2.3 to27.3±3.7 mV). Finally, formula number nine of CC (CC-NLC9) which composed of GMS (solid lipid), CapryolTM 90 (liquid lipid) and Lutrol® F127: Cremophore® RH (surfactants combination) was selected as the best formulation after the rank order for further investigations in the next work. &#x0D; Peer Review History: &#x0D; UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.&#x0D; Received file &#x0D; &#x0D; Average Peer review marks at initial stage: 5.0/10&#x0D; Average Peer review marks at publication stage: 7.5/10&#x0D; Reviewer(s) detail:&#x0D; Name: Dr. Mohammed Abdel-Wahab Sayed Abourehab&#x0D; Affiliation: Umm Al-Qura University; Makkah Al-Mukarramah, Saudi Arabia&#x0D; E-mail: maabourehab@uqu.edu.sa&#x0D; &#x0D; Name: Dr. Maha Khalifa Ahmed Khalifa &#x0D; Affiliation: Al-Azhar Universit - Cairo, Egypt&#x0D; E-mail: mahakhalifa.ahmed@hotmail.com&#x0D; &#x0D; Name: Dr. Evren Alğin Yapar&#x0D; Affiliation: Turkish Medicines and Medical Devices Agency, Turkiye&#x0D; E-mail: evren.yapar@yahoo.com&#x0D; Comments of reviewer(s): &#x0D; &#x0D; Similar Articles:&#x0D; FORMULATION AND CHARACTERIZATION OF TOPICAL NANO EMULGEL OF TERBINAFINE &#x0D; A REVIEW ON GOLD NANOPRTICLES SYNTHESIS AND CHARACTERIZATION &#x0D; FORMULATION AND EVALUATION OF ELASTIC LIPOSOMES OF DECITABINE PREPARED BY ROTARY EVAPORATION METHOD

Nanostructured Lipid Carriers Loaded with 17-α-Estradiol Accumulate into Hair Follicles

To improve 17-α-estradiol targeting in alopecia treatment, a formulation of nanostructured lipid carrier (NLC) prepared by the sonication method was developed. The physicochemical characterization showed an average diameter of 96 ± 15 nm and the average zeta potential of -17 ± 6 mV. In addition, the encapsulation efficiency (EE) of 17-α-estradiol, assessed by ultra-performance liquid chromatography (UPLC) fluorescence, was 99.6 ± 0.3%. Physical stability of NLC stored at room temperature was followed for 42 days through several physicochemical parameters, such as diameter, zeta potential, pH and EE. No changes were observed in the physicochemical parameters during this period, demonstrating the potential of NLC as a delivery system of 17-α-estradiol. NLC dermal penetration, investigated by Franz diffusion cell and confocal microscopy using rhodamine-labeled NLCs, showed an accumulation of NLC in the outer portions of the epidermis, precisely in the hair follicle. The NLCs distribution in the skin suggests that 17-α-estradiol targeting was improved.

Further Development of Near-Infrared Mediated Quantum Dots and Paclitaxel Co-loaded Nanostructured Lipid Carrier System for Cancer Theragnostic.

Of colloidal systems, ceteris paribus, nanostructured lipid carriers are second to none in offering a single-unit platform for multifunctional benefits. Quantum dots are known to possess unique properties that make them ideal for imaging purpose and that they may be used for cancer detection. For several decades, paclitaxel has been the most effective drug against a wide range of solid tumours. Theragnostic nanomedicine provides a platform to monitor, evaluate, and individualize treatment in real time. Evaluation of cancer treatment outcome at an early stage therapy is key to increase survival prospects of a patient. Previously, a novel co-loaded nanostructured lipid carriers’ theragnostic system for parenteral administration was developed. The aim of this study was to further investigate the co-loaded nanostructured lipid carriers in order to provide interpretation necessary for preclinical elucidation of the formulation, in part. The co-loaded nanostructured lipid carriers were prepared by oil/water emulsification-solvent evaporation technique. In this study, stability and co-loaded nanostructured lipid carriers’ internalization by MCF 7 and HepG2 cells were investigated. The co-loaded nanostructured lipid carriers was stable at 4°C for 1 month. The formulation was successfully internalized by MCF-7 and HepG2 cells. Nevertheless, the co-loaded nanostructured lipid carrier was more apt for MCF-7 cells. This finding affirms the formulation to be the most appropriate for breast cancer treatment. In addition, if taken correctly by a patient for a month, the formulation would give true reflection of the contents’ amounts, the factor paramount to appropriate changes in treatment protocol. It can therefore safely be concluded that the co-loaded nanostructured lipid carrier formulation may be potentially an effective theragnostic translational system.

Nanostructured lipid carriers: A novel hair protective product preventing hair damage and discoloration from UV radiation and thermal treatment

The goal of this study was to investigate the protective effects of nanostructured lipid carriers (NLCs) and vitamin E loaded NLCs (Vit E-NLCs) on preventing hair damages and discoloration against UV radiation and thermal treatment. The NLCs and Vit E-NLCs were prepared using a high-pressure homogenization technique. At optimal conditions, they showed spherical particles with a mean particle size of ~140 nm and a polydispersity index of < 0.3. Up to 90% (w/w) vitamin E acetate incorporation efficacy was achieved. The protective efficacy of the model cream containing blank-NLCs (NLCs cream) or Vit E-NLCs (Vit E-NLCs cream) was investigated. Upon exposure to UV-light and heat, the FE-SEM images revealed that the hair treated with both NLCs creams showed a smoothness of hair surface similar to the virgin hair. In accordance with protein loss, they exhibited the least protein loss as compared to the hair treated with Vit-E cream, cream base and commercial products. The same trend was observed for the discoloration test, the hair treated with both NLCs creams demonstrated the lowest total color loss, as compared to other products. Comparing between two NLCs formulations, antioxidant Vit E-NLCs showed to promote the photoprotective effect against hair damage and discoloration slightly greater than blank NLCs, but it has no extra benefit for heat protection. Considered overall, the developed NLCs and Vit E-NLCs is a novel alternative for preventing hair damage and discoloration from daily UV and heat exposure.

Design and optimization of febuxostat loaded nano lipid carriers using full factorial design

Objectives This work aims to develop nanostructured lipid carriers (NLCs) to improve the oral bioavailability of febuxostat (FEB). Materials and Methods High shear homogenization, a well-known technique, followed by bath sonication with slight modifications was used to prepare FEB-loaded NLCs using oleic acid as liquid lipid and stearic acid as solid lipid. A total of 3² full factorial design was utilized to examine the effect of 2 independent variables, namely, X1 (liquid to solid lipid ratio) and X2 (surfactant concentration) on the Y1 (particle size) and Y2 (% entrapment efficiency) of the drug. The prepared NLCs were evaluated for particle size, polydispersity index, zeta potential, and (%) entrapment efficiency. Results The drug's highest solubility was found in the stearic (solid lipid) and oleic acid (liquid lipid), which were further chosen for NLC preparation. Result of the present study showed an increase in entrapment efficiency and a decrease in particle size with the increase in liquid lipid to solid lipid ratio. With increased surfactant concentration, a small particle size is observed. The optimized formulation's particle size and (%) entrapment efficiency was found to be 99 nm and 80%, respectively. The formulations' zeta potential and polydispersity index were found within the range. Compared to plain drug suspension, the optimized formulation showed higher drug release, which may be due to the presence of the higher amount of liquid lipid. The particles shown in the transmission electron microscopy were round in shape and have smooth surface. Stability studies showed that the NLC formulation can be stored for a longer time period under room condition. Conclusion FEB-loaded NLC were successfully prepared using full 3² factorial design, and can be further used for oral delivery of FEB for gout treatment.

Design and Optimization of Nanostructured Lipid Carrier Containing Dexamethasone for Ophthalmic Use.

The aim of this study was to perform a preformulation study of dexamethasone (DXM)-loaded nanostructured lipid carriers (NLCs) for ocular use. Lipid screening was applied to find the most suitable solid and liquid lipids and surfactant for the NLC formulation. The visual observation was proved with XRD measurements for the establishment of the soluble state of DXM. Thermoanalytical measurements indicated that the most relevant depression of the crystallinity index could be ensured when using a 7:3 solid lipid:oil ratio. In order to optimize the NLC composition, a 23 full factorial experimental design was used. It was established that each independent factor (lipid, DXM, and surfactant concentration) had a significant effect on the particle size while in the case of entrapment efficiency, the DXM and surfactant concentrations were significant. Lower surfactant and lipid concentrations could be beneficial because the stability and the entrapment efficacy of NLCs were more favorable. The toxicity tests on human cornea cells indicated good ophthalmic tolerability of NLCs. The in vitro drug release study predicted a higher concentration of the solute DXM on the eye surface while the Raman mapping penetration study on the porcine cornea showed a high concentration of nanocarriers in the hydrophylic stroma layer.

Optimization and in vitro/in vivo performance of paclitaxel-loaded nanostructured lipid carriers for breast cancer treatment

Despite the wide use of paclitaxel (PTX) as antitumor drug, its intravenous administration is still limited by the low aqueous solubility (<1.0 μg/mL; log P = 3.96). Taxol® is the main commercial PTX-based product, but the high concentration of surfactant and ethanol necessary for PTX solubilization is usually associated with severe toxic effects. The incorporation of PTX into lipid nanocarriers has been considered an interesting nontoxic alternative to Taxol®, however, the drug loading is usually low. Thus, our main goal was to incorporate PTX in nanostructured lipid carriers (NLC) with high encapsulation efficiency and suitable characteristics for the evaluation of in vitro and in vivo biological responses. The optimized NLC formulation presented average size of 213 ± 9 nm, negative zeta potential (−18 ± 3 mV) and high encapsulation (0.9 mg/mL), as confirmed by FTIR and XRD analyses. The in vitro cytotoxic and anti-clonogenic effects of NLC-PTX against MDA-MB-231 cells were significantly higher than free PTX, and no significant cytotoxicity was found against L929 fibroblast cells. Radiolabeling of NLC-PTX with 99mTc was successfully attained (over 90% radiopurity) and stable in saline and mice plasma. The 99mTc-NLC-PTX showed a tumor accumulation 1.5- and 1.7-fold higher than the 99mTc-PTX dispersion in tumor-bearing mice after 30 and 120 min of post-administration, respectively. Therefore, PTX was successfully incorporated into NLC, with physicochemical characteristics suitable for intravenous administration, and with suggestive collaborative use in new strategies for the treatment of breast cancer.