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[Display omitted] Doxorubicin hydrochloride (DOX) is an anticancer agent used in cancer chemotherapy. The purpose of this study was to design nanostructured lipid carriers (NLCs) of DOX as smart chemotherapy to improve its photostability and anticancer efficacy. The characteristics of DOX and DOX-loaded NLCs were investigated using UV–Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, particle size, and zeta potential study. The cytotoxicity of DOX was evaluated against three cancer cell lines (HeLa, A549, and CT-26). The particle size and zeta potential were in the range 58.45-94.08 nm and −5.80 mV - −18.27 mV, respectively. The chemical interactions, particularly hydrogen bonding and van der Waals forces, between DOX and the main components of NLCs was confirmed by FTIR. NLCs showed the sustained release profile of DOX. The photostability results revealed that the NLC system improved the photostability of DOX. Cytotoxicity results using the three cell lines showed that all formulations improved the anticancer efficacy of free DOX, and the efficacy was dependent on cell type and particle size. These results suggest that DOX-loaded NLCs are promising chemotherapeutic agents for cancer treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] In view of the strong anti-inflammatory activity of glucocorticoids (GC) they are used in the treatment of almost all inflammatory lung diseases. In particular, inhaled GC (IGC) allow high drug concentrations to be deposited in the lung and may reduce the incidence of adverse effects associated with systemic administration. However, rapid absorption through the highly absorbent surface of the lung epithelium may limit the success of localized therapy. Therefore, inhalation of GC incorporated into nanocarriers is a possible approach to overcome this drawback. In particular, lipid nanocarriers, which showed high pulmonary biocompatibility and are well known in the pharmaceutical industry, have the best prospects for pulmonary delivery of GC by inhalation. This review provides an overview of the pre-clinical applications of inhaled GC-lipid nanocarriers based on several key factors that will determine the efficiency of local pulmonary GC delivery: 1) stability to nebulization, 2) deposition profile in the lungs, 3) mucociliary clearance, 4) selective accumulation in target cells, 5) residence time in the lung and systemic absorption and 6) biocompatibility. Finally, novel preclinical pulmonary models for inflammatory lung diseases are also discussed. [ABSTRACT FROM AUTHOR]

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

Graphical abstract Abstract Nanostructured lipid carriers (NLC) are biocompatible and biodegradable nanoscale systems with extensive application for controlled drug release. However, the development of optimal nanosystems along with a reproducible manufacturing process is still challenging. In this study, a two-step experimental design was performed and databases were successfully modelled using Artificial Intelligence techniques as an innovative method to get optimal, reproducible and stable NLC. The initial approach, including a wide range of values for the different variables, was followed by a second set of experiments with variable values in a narrower range, more suited to the characteristics of the system. NLC loaded with rifabutin, a hydrophobic drug model, were produced by hot homogenization and fully characterized in terms of particle size, size distribution, zeta potential, encapsulation efficiency and drug loading. The use of Artificial Intelligence tools has allowed to elucidate the key parameters that modulate each formulation property. Stable nanoparticles with low sizes and polydispersions, negative zeta potentials and high drug loadings were obtained when the proportion of lipid components, drug, surfactants and stirring speed were optimized by FormRules® and INForm®. The successful application of Artificial Intelligence tools on NLC formulation optimization constitutes a pioneer approach in the field of lipid nanoparticles. [ABSTRACT FROM AUTHOR]

Voriconazole-loaded nanostructured lipid carriers (VOR-NLC) were developed and drug penetration evaluated in porcine hooves in vitro . Synergistic effect of urea (Ur), selected among other known chemical enhancers according to hoof hydration potential, was also evaluated. VOR-NLC presented a high encapsulation efficiency (74.52 ± 2.13%), approximate mean diameter of 230 nm and were positively charged (+27.32 ± 2.74 mV). Stability studies indicated they were stable under refrigeration (4 ± 2 °C) for up to 150 days. SEM images revealed hooves treated with VOR-NLC and VOR-NLC-Ur suffered a disturbance on the surface depicting high roughness and porosity. Permeation data showed a substantial VOR amount retained in superficial hooves sections independent of the formulation used (2.42 ± 0.26; 2.52 ± 0.36 and 2.41 ± 0.60 μg/cm 2 for unloaded VOR, VOR-NLC and VOR-NLC-Ur, respectively, p > 0.05). Still, successive extractions, revealed the amount of VOR retained in deeper regions was significantly higher when VOR-NLC or VOR-NLC-Ur was used (0.17 ± 0.04, 0.47 ± 0.14 and 0.36 ± 0.07 μg/cm 2 for unloaded VOR, VOR-NLC and VOR-NLC-Ur, respectively, p < 0.05). Such results indicate NLC are promising formulations for the management of onychomycosis. Further studies in diseased nail plates are necessary. [ABSTRACT FROM AUTHOR]

The short time of action and systemic toxicity of local anaesthetics limit their clinical application. Bupivacaine is the most frequently used local anaesthetic in surgical procedures worldwide. The discovery that its S(−) enantiomeric form is less toxic than the R(+) form led to the introduction of products with enantiomeric excess (S75:R25 bupivacaine) in the market. Nevertheless, the time of action of bupivacaine is still short; to overcome that, bupivacaine S75:R25 (BVC S75 ) was encapsulated in nanostructured lipid carriers (NLC). In this work, we present the development of the formulation using chemometric tools of experimental design to study the formulation factors and Raman mapping associated with Classical Least Squares (CLS) to study the miscibility of the solid and the liquid lipids. The selected formulation of the nanostructured lipid carrier containing bupivacaine S75:R25 (NLC BVC ) was observed to be stable for 12 months under room conditions regarding particle size, polydispersion, Zeta potential and encapsulation efficiency. The characterisation by DSC, XDR and TEM confirmed the encapsulation of BVC S75 in the lipid matrix, with no changes in the structure of the nanoparticles. The in vivo analgesic effect elicited by NLC BVC was twice that of free BVC S75 . Besides improving the time of action , no statistical difference in the blockage of the sciatic nerve of rats was found between 0.125% NLC BVC and 0.5% free BVC S75 . Therefore, the formulation allows a reduction in the required anaesthesia dose, decreasing the systemic toxicity of bupivacaine, and opening up new possibilities for different clinical applications. [ABSTRACT FROM AUTHOR]

In this study, five polysaccharides were applied as natural polymeric coating materials to prepare solid lipid nanoparticles (SLN) and nanostructure lipid carriers (NLC), and then the obtained lipid colloidal particles were transformed to solid powders by the innovative nano spray drying technology. The feasibility and suitability of this new technology to generate ultra-fine lipid powder particles were evaluated and the formulation was optimized. The spray dried SLN powder exhibited the aggregated and irregular shape and dimension, but small, uniform, well-separated spherical powder particles of was obtained from NLC. The optimal formulation of NLC was prepared by a 20–30% oleic acid content with carrageenan or pectin as coating material. Therefore, nano spray drying technology has a potential application to produce uniform, spherical, and sub-microscale lipid powder particles when the formulation of lipid delivery system is appropriately designed. [ABSTRACT FROM AUTHOR]

Nanostructured lipid carriers (NLCs) are generally recognized as safe (GRAS) to form a controlled nanostructure are a new generation of lipid nanoparticles. In addition to formulation and particle surface properties, particle size had great influence for overcoming gastrointestinal (GI) barriers on the oral drug delivery of lipid based nanoparticles. In the present study, we investigated the effect of size on oral drug delivery for NLCs. The NLCs with different particle sizes (NLCs 100 nm, NLCs 200 nm and NLCs 300 nm) were prepared by using solvent evaporation method and the coumarin-6 (C6) or DiO/DiI was loaded in the nanoparticles as the fluorescence probe. The MTT assay indicated that both blank NLCs and C6-loaded NLCs displayed relatively low toxicity towards Caco-2 cells. Cellular uptake mechanisms of NLCs with different sizes were found to be similar and governed by active endocytosis, clathrin- and caveolae-mediated process. However, the smaller nanoparticle (NLC–100 nm) showed higher uptake efficiency in Caco-2 cell ( P < 0.05) as well as higher permeation ability in Caco-2 cell monolayer ( P < 0.01), compared with NLC–200 nm and NLC–300 nm. The fluorescence resonance energy transfer (FRET) assay indicated that all of three NLCs could maintained the structural integrity in blood circulation after oral administration. NLC–100 nm exhibited the most stability according to the most stable FRET signal. In situ rat intestinal absorption experiments and in vitro ligated rat intestinal loops model demonstrated that all NLCs could rapidly penetrate duodenum versus jejunum, ileum and colon ( P < 0.01). Moreover, pharmacokinetic studies showed that NLC–100 nm exhibited highest C max and AUC compared with the other two NLCs. In conclusion, the size of 100 nm might be the most suitable size for oral drug delivery of lipid based nanoparticles. [ABSTRACT FROM AUTHOR]

[Display omitted] Cancer treatments are always associated with various challenges, and scientists are constantly trying to find new therapies and methods. Erlotinib (ELT) is a well-known medicine against non-small cell lung cancer (NSCLC). However, treatments by ELT disrupt therapy due to drug resistance and pose severe challenges to patients. To achieve high-performance treatment, we gained nanostructured lipid carriers (NLCs) to evaluate synergistic anticancer effects of co-delivery of ELT and resveratrol (RES), a natural herbal derived phenol against NSCLC. NLCs are prepared via the hot homogenization method and characterized. In vitro cytotoxicity of formulations were evaluated on adenocarcinoma human alveolar basal epithelial (A549) cells. Prepared NLCs showed a narrow particle size (97.52 ± 17.14 nm), negative zeta potential (-7.67 ± 4.55 mV), and high encapsulation efficiency (EE%) was measured for the prepared co-delivery system (EE% 89.5 ± 5.16 % for ELT and 90.1 ± 6.61 % for RES). In vitro outcomes from cell viability study (12.63 % after 48 h of treatment), apoptosis assay (85.50%.), cell cycle (40.00% arrest in G2-M), and western blotting investigations (decreasing of protein expression levels of survivin, Bcl-2, P-Caspase 3P-caspase 9, and P-ERK 1/2, and additionally, increasing protein levels of BAX, P53, C-Caspase 3 and 9), DAPI staining, and colony formation assays showed the augment cytotoxic performances for co-delivery of ELT and RES loaded NLCs. Our study introduced the co-delivery of ELT and RES by NLCs as a novel strategy to elevate the efficacy of chemotherapeutics for NSCLC. [ABSTRACT FROM AUTHOR]

Daidzein is one of the most effective candidates for treating cardiovascular and cerebrovascular disease. However, considering its poor oral absorption and limited bioavailability, daidzein-loaded nanostructured lipid carriers-PLGA nanofibers were designed to handle the drawbacks. Daidzein-NLCs were successfully prepared by an emulsification and low-temperature solidification method. The physicochemical characteristics of NLCs were evaluated afterwards. Based on the preparation of daidzein-loaded NLCs, Daidzein-NLCs-nanofibers were optimized by electrospinning and were observed under Scanning Electron Microscope to capture the appearance. The sustained release profile of daidzein from Daidzein-NLCs-nanofibers in vivo was best fitted to the Kormeyer-Peppas equation. The in vitro skin permeable behavior showed the cumulative amount of daidzein from Daidzein-NLCs-nanofibers reached 21.71 μg cm −2 at 60 h, which was 3.78 times higher than pure daidzein solution. It demonstrated that the Daidzein-NLCs-nanofibers could significantly enhance the transported amount of drug. Confocal Laser Scanning Microscopy resulting images revealed a more effective content accumulation of Daidzein-NLCs-nanofibers than Daidzein-NLCs in epidermis. In vivo study indicated that Daidzein-NLCs-nanofibers had better skin retention than Daidzein-NLCs in the long term. The skin irritation experiment showed a positive result with no obvious stimulus observed. These results suggested that Daidzein-NLCs-nanofibers could be a potential candidate for transdermal delivery. [ABSTRACT FROM AUTHOR]

Nanoparticulate delivery systems have recently been under consideration for topical ophthalmic drug delivery. Brimonidine base-loaded solid lipid nanoparticles and nanostructured lipid carrier formulations were prepared using glyceryl monostearate as solid lipid and were evaluated for their physical stability following sterilization by autoclaving at 121 ° C for 15 min. The objective of this work was to evaluate the effect of autoclaving on the physical appearance, particle size, polydispersity index, zeta potential, entrapment efficiency and particle morphology of the prepared formulations, compared to non-autoclaved ones. Results showed that, autoclaving at 121 ° C for 15 min allowed the production of physically stable formulations in nanometric range, below 500 nm suitable for ophthalmic application. Moreover, the autoclaved samples appeared to be superior to non-autoclaved ones, due to their increased zeta potential values, indicating a better physical stability. As well as, increased amount of brimonidine base entrapped in the tested formulations. [ABSTRACT FROM AUTHOR]

[Display omitted] Piperine (PIP) is a herbal drug with well-known anticancer activity against different types of cancer including hepatocellular carcinoma. However, low aqueous solubility and extensive first-pass metabolism limit its clinical use. In this study, positively charged PIP-loaded nanostructured lipid carriers (PIP-NLCs) were prepared via melt-emulsification and ultra-sonication method followed by pectin coating to get novel pectin-coated NLCs (PIP-P-NLCs) targeting hepatocellular carcinoma. Complete in vitro characterization was performed. In addition, cytotoxicity and cellular uptake of nanosystems in HepG2 cells were evaluated. Finally, in vivo anticancer activity was tested in the diethylnitrosamine-induced hepatocellular carcinoma mice model. Successful pectin coating was confirmed by an increased particle size of PIP-NLCs from 150.28 ± 2.51 nm to 205.24 ± 5.13 nm and revered Zeta potential from 33.34 ± 3.52 mV to −27.63 ± 2.05 mV. Nanosystems had high entrapment efficiency, good stability, spherical shape, and sustained drug release over 24 h. Targeted P-NLCs enhanced the cytotoxicity and cellular uptake compared to untargeted NLCs. Furthermore, PIP-P-NLCs improved in vivo anticancer effect of PIP as proved by histological examination of liver tissues, suppression of liver enzymes and oxidative stress environment in the liver, and alteration of cell cycle regulators. To conclude, PIP-P-NLCs can act as a promising approach for targeted delivery of PIP to hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

In past years, nanostructured lipid carriers (NLCs) have emerged as novel topical antioxidant delivery systems because of combined positive features of liposomes and polymeric nanoparticles. Here, we seek to unlock the possibility of idebenone (IDB; an antioxidant)-loaded NLCs (IDB–NLCs) cellular interactions such as, viability and uptake, and its photoprotective effects against Ultraviolet-B (UVB)-mediated oxidative stress in immortal human keratinocyte cell line (HaCaT). The two-step preformulation strategy followed by three-level, three-variable, L 9 (3 3 ) Taguchi robust orthogonal design employed was important in improving IDB–NLCs key physicochemical aspects such as, entrapment efficiency, drug release (sustained), occlusion, skin deposition and physical stability. UV crosslinker, confocal microscopy and flow cytometry techniques were used to (1) mediate oxidative stress in HaCaT cells, (2) study a qualitative cellular uptake, (3) measure intracellular reactive oxygen species (ROS), and mitochondrial membrane potential, respectively. NLCs markedly improved biocompatibility of IDB under normal as well as stress conditions. Quantitative and qualitative cell uptake studies demonstrated a significant uptake of IDB–NLCs (3-fold increase) and nile red-labeled IDB–NLCs (NR–IDB–NLCs) at 2 h, respectively, hence exerted improved photoprotective effects. [ABSTRACT FROM AUTHOR]

Nanostructured lipid carriers (NLC) are interesting delivery systems for enhancing the penetration of an active substance through the skin after topical administration. In the present study, lycopene was loaded into NLC, composed of Eumulgin ® SG, orange wax and rice bran oil, using high pressure homogenization (HPH). Photon correlation spectroscopy analysis showed that the lycopene-loaded NLC had a size of 150–160 nm with a relatively small size distribution (PdI < 0.15). The entrapment efficiency of lycopene was found to be 100 ± 0% for all formulations. An in vitro release study of lycopene showed a biphasic release profile: a relatively fast release during the first 6 h followed by a sustained release during the next 18 h. An in vitro occlusion test showed that the occlusive properties of NLC increased with increasing lycopene loading. A free radical scavenging activity test of the NLC loaded with 50 mg% lycopene showed a Trolox equivalent antioxidant capacity value of 36.6 ± 0.4 μM Trolox/mg NLC which is higher than that of the NLC base (26.6 ± 0.1 μM Trolox/mg NLC). The concentration of 50% antioxidant activity (IC 50 ) of the lycopene-loaded NLC was 14.1 ± 0.6 mg/mL, and lower than that of the formulation without lycopene (17.7 ± 0.4 mg/mL). The particle size, size distribution, and zeta potential of lycopene-loaded NLC stored at different temperatures of 4, 30, 40 °C for 120 days did not change in time, demonstrating an excellent colloidal stability of the systems. Chemical stability data indicated that the utilization of NLC increased the stability of lycopene and it was found that the degradation of lycopene was retarded when stored at low temperatures. In conclusion, NLC are attractive systems for the cutaneous delivery of lycopene. [ABSTRACT FROM AUTHOR]

[Display omitted] 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 (D 12 DAB) and oleic acid and used these to co-encapsulate a Pam 2 CS 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. [ABSTRACT FROM AUTHOR]

The present study investigates the screening of the formulation components as well as evaluates the quality issues of the nanostructured lipid carriers (NLCs) for the anticancer agent, CPT-11. The stepwise screening of the components for the preparation of NLCs requires the selection of liquid lipid or oil, based on the relative solubility of CPT-11 in different oils. Maximum solubility of the CPT-11 was found in capmul MCM-C8 (81±0.5mg/ml). Hence, it was selected as the liquid lipid for the development of NLCs. Solid lipids gelucire 39/1, glyceryl mono stearate (GSM) and compritol ATO 888 were observed to have good affinity for the drug on systematic screening of different solid lipids. However, gelucire 39/1 and GSM were found to have lower physical compatibility (miscibility) with capmul MCM C-8. Hence, compritol ATO 888 was selected as the solid lipid phase for the preparation of NLCs. Ratio of liquid lipid (oil) to solid lipid was optimized with the intention of maximizing the oil concentration (as oil was found to have higher solubility of drug) as well as producing a lipid mix with sufficient melting point to maintain solid state. The liquid–solid lipid mixture in the ratio up to 30:70 was observed to have sufficient melting point (52.48±1.2°C). Pluronic F-68 was selected as the main surfactant for the preparation of NLCs because of its good emulsification efficacy for the solid lipid liquid mix. The optimized formulation was also evaluated for the different quality issues. PXRD data revealed that the characteristic peaks of the compritol were present in the NLC samples and there was no appreciable polymorphic change when the formulation was stored for 6 months. Electron microscopic and DLS studies proved the absence of different colloidal species. Thermal analysis by DSC revealed that the lipid particles maintained sufficiently good melting point even after nanosizing. Absence of gelation on multiple syringing and resilience for the stress provided by autoclaving further established the quality of the developed NLCs. [ABSTRACT FROM AUTHOR]

Abstract: Long chain lipid (LCL) based tamoxifen loaded nanostructured lipid carriers (Tmx-NLCs) meant to target intestinal lymphatic systems (ILSs) was developed and characterized previously. The aim of the present work was to evaluate in vitro efficacy of developed Tmx-NLC against breast cancer cell lines and to confirm the hypothesis of targeting ILS after single dose oral administration. In vitro anticancer activity of Tmx-NLC was assessed in human estrogen receptor expressing breast cancer cell lines viz. MCF-7 and ZR-75-1. The study revealed relatively improved activity for Tmx-NLC compared to free Tmx against MCF-7 cells. However, the activity was compromised against ZR-75-1 cells which could be attributed to its up regulation of MUC1 gene. Confocal and flow cytometric analysis revealed remarkable intracellular uptake of Tmx-NLC and its localization in nuclear and perinuclear region of cells. Tmx-NLC exhibited distinctly different pharmacokinetic profile compared to Tamoxifen suspension (Tmx-susp) and exhibited an increment in the bioavailability by 2.71-fold and prolonged the T 1/2 by 7.10-fold. Moreover, detectable drug concentration in mesenteric lymph nodes justifies our hypothesis of targeting ILS and explains the major uptake of Tmx to occur via lymphatic system. [Copyright &y& Elsevier]

The targeting ability of pentapeptide (Thr-Lys-Pro-Pro-Arg) grafted nanostructured lipid carriers (Pen-NLCs) to macrophages was investigated in both in vitro and in vivo studies. The results showed the improvement of the anti-inflammatory effect by using this drug delivery system. Firstly, a pentapeptide-polyethylene glycol2000-stearate was synthesized and formulated into Pen-NLCs. Non-grafted nanostructured lipid carriers (Bare-NLCs) and Pen-NLCs were 190.0±1.0 and 203.0±8.5nm in size, −8.1±2.1 and 2.3±1.2mV in zeta potential respectively. Meanwhile, they had comparable entrapment efficiency and drug loading efficiency. In vitro and in vivo cellular uptake studies showed increased internalization of Pen-NLCs by macrophages when compared to pure drugs and Bare-NLCs. Animal studies in a carrageenan-treated air pouch model were used to further investigate the anti-inflammatory effects of Pen-NLCs. Through intravenous administration, a single dose of DXM loaded Pen-NLCs showed the strongest inhibition of inflammatory indexes of air pouch fluid weight, leukocyte infiltration, granulation tissue weight and nitric oxide concentration in comparison with free drugs and DXM loaded Bare-NLCs. In conclusion, this study demonstrated the potential of Pen-NLCs as promising drug carriers for anti-inflammatory treatments. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of the present investigation was to explore feasibility of nanocarrier based transdermal delivery of Huperzine A (HupA) for the treatment of Alzheimer''s disease. For this investigation, microemulsion (ME), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) were formulated and characterized for physicochemical parameters. The pseudo-ternary phase diagrams for microemulsion region were developed using generally recognized as safe (GRAS) excipients. The SLNs and NLCs were prepared by microemulsion template technique. These nanodispersions were formulated into gels for transdermal application and evaluated for various physicochemical parameters. In vitro permeation profiles in rat skin exhibited zero-order kinetics. HupA loaded ME exhibited superior permeation than NLCs followed by SLNs and cumulative amount permeated after 24h was found to be 147.68±9.42μg/cm2, 129.11±32.76μg/cm2 and 10.74±0.68μg/cm2, respectively. Furthermore, optimized gels were subjected to primary skin irritation testing over a period of 48h and were found to be safe for skin application. In vivo efficacy tested in scopolamine induced amnesia model indicated significant improvement in cognitive function in mice group treated with developed nanocarrier based formulations as compared to the control group. [Copyright &y& Elsevier]

Abstract: Nanostructured lipid carriers (NLC)-based gel was developed as potential topical system for flurbiprofen (FP) topical delivery. The characterizations of the prepared semisolid formulation for topical application on skin were assessed by means of particle size distribution, zeta potential analysis, X-ray analysis, in vitro percutaneous penetration, rheological study, skin irritation test, in vivo pharmacodynamic evaluation and in vivo pharmacokinetic study. The NLC remained within the colloidal range and it was uniformly dispersed after suitably gelled by carbopol preparation. It was indicated in vitro permeation studies through rat skin that FP-NLC-gel had a more pronounced permeation profile compared with that of FP-loaded common gel. Pseudoplastic flows with thixotropy were obtained for all NLC-gels after storage at three different temperatures. No oedema and erythema were observed after administration of FP-NLC-gel on the rabbit skin, and the ovalbumin induced rat paw edema could be inhibited by the gel. The maximum concentration in plasma was 29.44μg/ml and 2.49μg/ml after oral and topical administration, respectively. While the amount of drug accumulated in skin after topical application was much higher than oral application. In conclusion, NLC-based gel could be a promising vehicle for topical delivery of FP. [Copyright &y& Elsevier]

Abstract: The main objective of this study was to evaluate the potential of Quercetin-loaded nanostructured lipid carriers (QT-NLCs) as a topical delivery system. QT-NLCs were prepared by the method of emulsion evaporation–solidification at low temperature. The average entrapment efficiency and drug loading of the optimized QT-NLCs were 89.95±0.16% and 3.05±0.01%, respectively. Under the transmission electron microscope, the nanoparticles were spherically shaped. The average particle size was 215.2nm, the zeta potential was −20.10±1.22mV and pH value of QT-NLCs system was 4.65. Topical delivery of QT in the form of NLCs was investigated in vitro and in vivo. The results showed that QT-NLCs could promote the permeation of QT, increase the amount of QT retention in epidermis and dermis, and enhance the effect of anti-oxidation and anti-inflammation exerted by QT. Then the mechanism of NLCs for facilitating drug penetration was further investigated through histological sections. In conclusion, NLCs could be a promising vehicle for topical delivery of QT. [Copyright &y& Elsevier]

Abstract: Itraconazole-loaded NLC for pulmonary application were developed. In Precirol ATO 5 and oleic acid Itraconazole had the highest solubility. The solid lipid and the oil were mixable in a ratio 9:1 possessing a melting point above body temperature. 0.4% Itraconazole was dissolved in this lipid blend. Eumulgin SLM 20 was the stabilizer with the highest affinity to the lipid blend used as particle matrix. 2.5% Eumulgin SLM 20 was sufficient to obtain NLC with a narrow particle size distribution and sufficient stability. The tonicity of the formulation was adjusted with glycerol. Sterility was obtained by autoclaving. Neither the addition of glycerol nor autoclaving had an influence on the particle size and the zeta potential of Itraconazole-loaded NLC. SEM images showed spherical particles confirming the particle size measured by light scattering techniques. An entrapment efficiency of 98.78% was achieved. Burst release of Itraconazole from the developed carrier system was found. Itraconazole-loaded NLC possessed good storage stability. Nebulizing Itraconazole-loaded NLC with a jet stream and an ultrasonic nebulizer had no influence on the particle size and the entrapment efficiency of Itraconazole in the particle matrix, being a precondition for pulmonary application. [Copyright &y& Elsevier]

Abstract: Nanostructured lipid carrier (NLC) system of simvastatin was investigated for improvement in release, pharmacokinetics and biodistribution over its solid lipid nanoparticles (SLN). The NLC formulations prepared by solvent injection technique were optimized by 23 full factorial design. Optimized NLC was deduced on the basis of dependent variables that were analyzed using Design expert 8.0.2® software (Stat Ease, Inc., USA). Pareto charts and response surface plots were utilized to study the effect of variables on the response parameters. The optimized NLC was a suspension of nanosized homogeneous particles with significantly higher entrapment efficiency (>90%) and lower recrystallization properties (p <0.01) than SLNs. The pharmacokinetic parameters of Tc99 labeled optimized NLC in mice, obtained using Quickcal software (Plexus, India) revealed 4.8 folds increase in bioavailability as compared to simvastatin suspension and 2.29 folds as compared to SLNs. Biodistribution study revealed preferential accumulation of NLC in the liver and this is advantageous because liver is the target organ for simvastatin. IVIVC studies demonstrated level A correlation between in vitro release and percent drug absorbed. This investigation demonstrated the superiority of NLC over SLN for improved oral delivery and it was deduced that the liquid lipid, oleic acid was the principal formulation factor responsible for the improvement in characteristics, pharmacokinetics and biodistribution of NLCs. [Copyright &y& Elsevier]

Abstract: Topical application of lutein as an innovative antioxidant, anti-stress and blue light filter, which is able to protect skin from photo damage, has got a special cosmetic and pharmaceutical interest in the last decade. Lutein is poorly soluble, and was therefore incorporated into nanocarriers for dermal delivery: solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and a nanoemulsion (NE). Nanocarriers were produced by high pressure homogenization. The mean particle size was in the range of about 150nm to maximum 350nm, it decreased with increasing oil content of the carriers. The zeta potential in water was in the range −40 to −63mV, being in agreement with the good short term stability at room temperature monitored for one month. In vitro release was studied using a membrane free model. Highest release in 24h was observed for the nanoemulsion (19.5%), lowest release (0.4%) for the SLN. Release profiles were biphasic (lipid nanoparticles) or triphasic (NE). In vitro penetration study with a cellulose membrane showed in agreement highest values for the NE (60% in 24h), distinctly lower values for the solid nanocarriers SLN and NLC (8–19%), lowest values for lutein powder (5%). Permeation studies with fresh pig ear skin showed that no (SLN, NLC) or very little lutein (0.4% after 24h) permeated, that means the active remains in the skin and is not systemically absorbed. The nanocarriers were able to protect lutein against UV degradation. In SLN, only 0.06% degradation was observed after irradiation with 10 MED (Minimal Erythema Dose), in NLC 6–8%, compared to 14% in the NE, and to 50% as lutein powder suspended in corn oil. Based on size, stability and release/permeation data, and considering the chemical protection of the lutein prior to its absorption into the skin, the lipid nanoparticles are potential dermal nanocarriers for lutein. [Copyright &y& Elsevier]

Abstract: The two polyhydroxy surfactants polyglycerol 6-distearate (Plurol®Stearique WL1009 – (PS)) and caprylyl/capryl glucoside (Plantacare® 810 – (PL)) are a class of PEG-free stabilizers, made from renewable resources. They were investigated for stabilization of aqueous solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) dispersions. Production was performed by high pressure homogenization, analysis by photon correlation spectroscopy (PCS), laser diffraction (LD), zeta potential measurements and differential scanning calorimetry (DSC). Particles were made from Cutina CP as solid lipid only (SLN) and its blends with Miglyol 812 (NLC, the blends containing increasing amounts of oil from 20% to 60%). The obtained particle sizes were identical for both surfactants, about 200nm with polydispersity indices below 0.20 (PCS), and unimodal size distribution (LD). All dispersions with both surfactants were physically stable for 3 months at room temperature, but Plantacare (PL) showing a superior stability. The melting behaviour and crystallinity of bulk lipids/lipid blends were compared to the nanoparticles. Both were lower for the nanoparticles. The crystallinity of dispersions stabilized with PS was higher, the zeta potential decreased with storage time associated with this higher crystallinity, and leading to a few, but negligible larger particles. The lower crystallinity particles stabilized with PL remained unchanged in zeta potential (about −50mV) and in size. These data show that surfactants have a distinct influence on the particle matrix struture (and related stability and drug loading), to which too little attention was given by now. Despite being from the same surfactant class, the differences on the structure are pronounced. They are attributed to the hydrophobic–lipophilic tail structure with one-point anchoring in the interface (PL), and the loop conformation of PS with two hydrophobic anchor points, i.e. their molecular structure and its interaction with the matrix surface and matrix bulk. Analysis of the effects of the surfactants on the particle matrix structure could potentially be used to further optimization of stability, drug loading and may be drug release. [Copyright &y& Elsevier]

Abstract: The objective of the present study was to formulate and characterize Acitretin loaded Nanostructured Lipid Carriers (ActNLCs), to understand in vitro drug release and clinically evaluate the role of the developed gel in the topical treatment of psoriasis. ActNLCs were prepared by solvent diffusion technique using 32 full factorial design. The mean diameter and surface morphology of ActNLC was evaluated. ActNLCs were lyophilized and crystallinity of NLC was characterized by Differential Scanning Calorimtery (DSC) and powder X-Ray Diffraction (XRD). The NLCs were incorporated in 1% w/w Carbopol 934 P gel base and in vitro skin deposition studies in Human Cadaver Skin and double-blind clinical studies in psoriatic patients were conducted. The optimized ActNLCs were spherical in shape, with average particle size of 223(±8.92)nm, zeta potential of −26.4 (±0.86) mV and EE of 63.0(±1.54)%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of Acitretin was found in human cadaver skin from ActNLC gel (81.38 ±1.23%) as compared to Act plain gel (47.28±1.02%). Clinical studies demonstrated significant improvement in therapeutic response and reduction in local side effects with ActNLCs loaded gel indicated its effectiveness in the topical treatment of Psoriasis. [ABSTRACT FROM AUTHOR]

Abstract: Enhancement of the chemical stability of ascorbyl palmitate (AP) after incorporation into nanostructured lipid carriers (NLC) has been reported. However, the formulation parameters of AP-loaded NLC have not been completely investigated. Moreover, the long-term chemical stability of AP in any colloidal systems has not been yet achieved. Therefore, in this study the formulation parameters affecting the stability of AP after incorporation into NLC were evaluated including types of lipids, types of surfactants, storage conditions, i.e. temperature and nitrogen gas flushing, the effects of drug loading as well as types of antioxidants. After storage for 90 days, the mean particle size analyzed by photon correlation spectroscopy (PCS) was lower than 350nm. The zeta potential measured by the Zetasizer IV was higher than −30mV in all developed AP-loaded NLC formulations which varied according to the types of lipid and surfactant. Concerning the chemical stability of AP, it was found that AP-loaded NLC prepared and stored in non-degassing conditions, a higher percentage of AP loading in NLC, lower storage temperature (4°C), addition of antioxidants as well as selection of suitable surfactants and solid lipids improved the chemical stability of AP. Moreover, an improvement of long-term chemical stability of AP was achieved by addition of antioxidants with nitrogen gas flushing as compared to those without antioxidant. The percentage of drug remaining at both 4°C and room temperature (25°C) was higher than 85% during 90 days of storage. [Copyright &y& Elsevier]

[Display omitted] The rate of infections caused by resistant bacteria to the antimicrobials available for human use grows exponentially every year, which generates major impacts on human health and the world economy. In the last two decades, human beings can witness the expressive increase in the Science and Technology worldwide, and areas such as Health Sciences have benefited from these advances in favor of human health, such as the advent of Pharmaceutical Nanotechnology as an important approach applied for bacterial infections treatment with resistance profile to available antibiotics. This review of the scientific literature brings the applicability of nanotechnology-based lipid systems as an innovative tool in the improvement of bacterial infections treatment. Important studies involving the use of liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, microemulsions and lipid nanocapsules were verified in the period from 2000 to 2020, where important scientific results were found and will serve as a basis for the use of these systems to remain in constant updating. This manuscript shows the use of these drug delivery systems as potential vehicles for antibacterial compounds, which opens a new hope in the complement of the antibacterial therapeutic arsenal. Important studies developed in the last 20 years are present in this review, and thus guarantees an update on the use of these drug delivery systems for researchers from different areas of Health Sciences. [ABSTRACT FROM AUTHOR]

[Display omitted] The present study aims to develop curcumin-loaded nanostructured lipid carriers (CUR-NLCs) and investigate their neuroprotective effects in lipopolysaccharide (LPS)-induced depression and anxiety model. Nanotemplate engineering technique was used to prepare CUR-NLCs with Compritol 888 ATO and oleic acid as solid and liquid lipid, respectively. Poloxamer 188, Tween 80 and Span 80 were used as stabilizing agents for solid–liquid lipid core. The physicochemical parameters of CUR-NLCs were determined followed by in vitro drug release and in vivo neuroprotective activity in rats. The optimized CUR-NLCs demonstrated nanometric particle size of 147.8 nm, surface charge of –32.8 mV and incorporation efficiency of 91.0%. CUR-NLCs showed initial rapid followed by a sustained drug release reaching up to 73% after 24 h. CUR-NLCs significantly elevated struggling time and decreased immobility time in forced swim and tail suspension tests. A substantial increase in time spent and number of entries into the light and open compartments was observed in light–dark box and elevated plus maze models. CUR-NLCs improved the tissue architecture and suppressed the expression of p -NF-κB, TNF-α and COX-2 in brain tissues from histological and immunohistochemical analysis. CUR-NLCs improved the neuroprotective effect of curcumin and can be used as a potential therapeutics for depression and anxiety. [ABSTRACT FROM AUTHOR]

[Display omitted] This study aims to design and characterize Nanostructured lipid carriers (NLC) and Nanostructured lipid carrier-based hydrogels with Passiflora edulis seeds oil, a by-product from Madeira Island food industry. NLC were prepared by the ultrasonication technique, using passion fruit seeds oil as a liquid lipid and glyceryl distearate as a solid lipid. These NLC were then gelled with Poly (acrylic acid). Long-term stability studies were conducted with NLC and NLC-based hydrogels stored for 12 months. The following tests were performed: morphology, encapsulation efficiency, particle size analysis, polydispersity index analysis, zeta potential, pH measurement, color analysis, viscosity studies, texture analysis, in vitro occlusion test, ex vivo skin penetration study, tyrosinase inhibition activity, in vitro skin permeation experiments and in vitro cytotoxicity studies. The developed NLC had spherical shape and narrow particle sizes distribution with mean sizes in the range of 150 nm and PDI below 0.3, Zeta potential values around −30 mV and high Encapsulation efficiency. The tyrosinase inhibitory activity and skin retention of the nanoparticles was superior to that of the non-encapsulated oil. The developed formulations did not show cytotoxicity towards HaCat cells and presented suitable viscosity and texture properties for skin application, proving to be good candidates as depigmenting agent. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nanostructured Lipid Carriers (NLC) were investigated in vivo to promote β-carotene skin permeation. • Unlike β-carotene and microparticles, the penetration depth of nanoparticles was sizedependent. • The smallest size (about 200 nm) penetrated more deeply into the stratum corneum (SC) barrier. • The goal of providing β-carotene actions against oxidative damages beyond the SC could be envisaged. Nanostructured Lipid Carriers (NLC) were investigated with the purpose of promoting skin permeation of the highly lipophilic β-carotene (BC) across the stratum corneum (SC) barrier so that it may perform its antioxidant properties in photo-aging and epithelial skin cancer prevention. Two differently sized NLC samples were developed using stearic acid and squalene as lipid matrix and evaluated in comparison with Microstructured Lipid Carriers (MLC). The carriers were characterized for morphology, size, Z-potential, BC loading and release as well as physical state by means of DSC and XRPD analyses. In vivo penetration of the carriers was assessed on humans by determining BC concentrations within the SC stratum disjunctum and stratum compactum layers removed by means of the tape stripping test in comparison with pure BC. Unlike MLC and pure BC that were mostly retained within the outermost layers of the SC, the NLC sample having the smallest size (about 200 nm) has proved to penetrate more deeply into the SC barrier. Accordingly, the goal of providing β-carotene actions against oxidative damages within the looser skin viable tissues could be envisaged. [ABSTRACT FROM AUTHOR]

• Lipid nanoparticles as promising drug delivery carriers for antituberculosis therapy. • Sustained drug release patterns are characteristic of antiTB-lipid nanoparticles. • Pharmacokinetic behaviors of lipid carriers are attractive for the treatment of TB. Tuberculosis is a topic of relevance worldwide because of the social and biological factors that triggered the disease and the economic burden on the health-care systems that imply its therapeutic treatment. Challenges to handle these issues include, among others, research on technological breakthroughs modifying the drug regimens to facilitate therapy adherence, avoid mycobacterium drug resistance, and minimize toxic side-effects. Lipid nanoparticles arise as a promising strategy in this respect as deduced from the reported scientific data. They are prepared from biodegradable and biocompatible starting materials and compared to the use of the free drugs, the entrapment of active molecules into the carriers might lead to both dose reduction and controlled delivery. Moreover, the target to the lung, the organ mainly affected by the disease, could be possible if the particle surface is modified. Although conclusive statements cannot be made considering the limited number of available research works, looking into what has been achieved up to now definitively encourages to continue investigations in this regard. [ABSTRACT FROM AUTHOR]

The purpose of this study was to enhance the anti-leishmanial efficacy of miltefosine (MTF) and reduce its toxic effects by loading it into nanostructured lipid carriers (NLCs). Micro-emulsion technique was used to prepare MTF-loaded NLCs. The optimized NLCs were characterized in terms of various physicochemical parameters including particle size, poly dispersity index (PDI), zeta potential, transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) technique. In vitro and in vivo assays were performed to evaluate the potential of NLCs as an effective nanocarrier system for oral delivery of MTF in Cutaneous Leishmaniasis. The optimized MTF-loaded NLCs exhibited mean particle size of 160.8 ± 5.3 nm with narrow PDI and high incorporation efficiency (IE%) of 96.17 ± 1.3%. MTF-loaded NLCs demonstrated slow release of the incorporated drug as compared to the drug solution. The optimized formulation showed significant decrease in hemolytic potential, 2.5~folds increase in anti-leishmanial efficacy and 6~fold decrease in macrophage cytotoxicity as compared to MTF solution, in vitro. Macrophage uptake study confirmed passive targeting ability of MTF-loaded NLCs. In-vivo analysis demonstrated enhanced anti-leishmanial effect of the MTF-loaded NLCs and better pharmacokinetic profiles with no gastrointestinal (GI) toxicity. NLCs are potential nanocarriers for the oral delivery of MTF with enhanced anti-leishmanial activity, better safety profile and reduced hemolytic potential. [ABSTRACT FROM AUTHOR]

• Formation of HIP enables high encapsulation efficiency of peptide in SLN and NLC. • Lipid-based nanocarriers were highly internalized by Caco-2 cell monolayers. • SLN and NLC were able to cross the mucus barrier (Caco-2/HT29-MTX cell model). • Peptide intestinal transport was limited by an extensive release from the carriers. Peptides are therapeutic molecules with high potential to treat a wide variety of diseases. They are large hydrophilic compounds for which absorption is limited by the intestinal epithelial border covered by mucus. This study aimed to evaluate the potential of Hydrophobic Ion Pairing combined with Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) to improve peptide transport across the intestinal border using Caco-2 cell monolayers (enterocyte-like model) and Caco-2/HT29-MTX co-cultured monolayers (mucin-secreting model). A Hydrophobic Ion Pair (HIP) was formed between Leuprolide (LEU), a model peptide, and sodium docusate. The marked increase in peptide lipophilicity enabled high encapsulation efficiencies in both NLC (84%) and SLN (85%). After co-incubation with the nanoparticles, confocal microscopy images of the cell monolayers demonstrated particles internalization and ability to cross mucus. Flow cytometry measurements confirmed that 82% of incubated SLN and 99% of NLC were internalized by Caco-2 cells. However, LEU transport across cell monolayers was not improved by the nanocarriers. Indeed, combination of particles platelet-shape and HIP low stability in the transport medium led to LEU burst release in this environment. Improvement of peptide lipidization should maintain encapsulation and enable benefit from nanocarriers enhanced intestinal transport. [ABSTRACT FROM AUTHOR]

The aim of this study was to fabricate nanostructured lipid carriers, NLCs, of nintedanib (BIBF) to improve its oral bioavailability. Two types of NLCs loaded with BIBF (BIBF-NLCs-1 and BIBF-NLCs-2) were prepared by the melt-emulsification technique. BIBF-NLCs-1 and BIBF-NLCs-2 showed nanoscale particle sizes of 142.70 ± 0.85 nm and 7.99 ± 0.06 nm, and both were positive zeta potential. Study on Caco-2 cells showed that BIBF-NLCs-1 exhibited distinct advantages at the cytological level. The oral bioavailability of BIBF-NLCs-1 and BIBF-NLCs-2 was extremely improved 3.13-fold and 2.39-fold respectively compared with BIBF solution (BIBF-Sol). And in vivo anti-tumor efficiency study in mice bearing LLC lung tumor indicated that BIBF-NLCs-1 and BIBF-NLCs-2 had excellent tumor inhibition. Besides, the two NLCs did not increase the risk of liver damage and can even reduce the incidence of gastrointestinal irritation of BIBF to some extent. In summary, NLCs are a potential oral delivery system to improve the bioavailability of BIBF by promoting intestinal absorption. [ABSTRACT FROM AUTHOR]

Excessive exposure to solar radiation induces injurious effects on human skin. Our previous study evidenced that protocatechuic acid (P0) and ethyl protocatechuate (P2) act against photodamage and photoaging. The present study aimed to develop solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for topical delivery of P0 or P2, as a strategy for photoprotection. Lipid nanoparticles exhibited mean particle size, polydispersity index, zeta potential and association efficiency between 200 and 400 nm, 0.160 to 0.460, −2.2 to −5.2 mV, and 60% to 80%, respectively. The formulations were stable for 3 months when stored at 4○C and 25○C/60% RH. SLNs/NLCs-P0 showed minor cytotoxicity effects compared with SLNs/NLCs-P2, in HaCat (keratinocytes) and HFF-1 (fibroblasts) cell lines. Additionally, bare NLCs exhibited less cytotoxicity effect, compared with bare SLNs. NLCs exhibited a controlled in vitro release of P0 and P2, and were able to protect the compounds against UVB degradation. Ex vivo permeability study showed that NLCs modulated P0 and P2 retention profiles on human skin layers. Furthermore, histological analysis of skin showed that NLCs-P0 did not cause morphological alterations, while NLCs-P2 showed a potential irritation effect in the skin structure. Based on these results, NLCs were considered a potential dermatological nanocarrier for P0 delivery. [ABSTRACT FROM AUTHOR]

The objective of the study was to assess the effect of enhanced mucoadhesion of a cationic mucoadhesive nanostructured lipid carrier (NLC) on its ocular disposition after topical administration. The NLC was made mucoadhesive by surface coating with chitosan oligosaccharide (COS), a low molecular weight derivate of chitosan which is more suitable for drug delivery applications as compared to the native chitosan. The NLC was characterised by surface evaluating techniques like SANS and XPS for confirming coating of COS over the surface of NLC. In order to assess the effect of COS coating on in vivo ocular mucoadhesion, coumarin loaded NLC were topically administered to rats and the sagittal sections of the eyes were imaged using confocal microscopy. The COS coated NLC were seen to adhere more around the ocular surface than the uncoated NLC during the 4-h study. The improved ocular retention for COS-NLC reflected on the content of Etoposide within the eye, which showed a higher concentration of Etoposide, as compared to the uncoated NLC. The NLC was also assessed for any ocular irritancy in rabbits and repeat dose toxicity in rats and found to be relatively non-irritant and non-toxic as compared to appropriate controls. Thus, the study asserts that to achieve higher concentration of therapeutics within the eye, the formulations like NLC are not just required to be permeating but also retentive on the surface of the eye to achieve appreciable concentrations. [ABSTRACT FROM AUTHOR]

The limited brain delivery of carbamezapine (CBZ) presents a major hurdle in the successful epilepsy treatment. The potential of carbamezapine-loaded nanostructured lipid carriers (CBZ-NLCs) for improved brain delivery is investigated in the current study. CBZ-NLCs were prepared by using binary mixture of trilaurin and oleic acid as a lipid core stabilized with Poloxamer 188, Tween 80 and Span 80. CBZ-NLCs were evaluated for physicochemical properties, in vitro release, in vivo brain kinetics, anticonvulsant and anxiolytic activities. The optimized CBZ-NLCs demonstrated nanometric particle size (97.7 nm), surface charge of −22 mV and high drug incorporation (85%). CBZ-NLCs displayed biphasic release pattern with initial fast followed by sustained drug release. CBZ-NLCs significantly enhanced the AUC of CBZ (520.4 µg·h/mL) in brain compared with CBZ dispersion (244.9 µg·h/mL). In vivo anticonvulsant activity of CBZ-NLCs in PTZ-induced seizure model showed a significant increase in the onset time (143.0 sec) and reduction in duration (17.2 sec) of tonic-clonic seizures compared with CBZ dispersion (75.4 and 37.2 sec). The anxiolytic activity in light-dark box and elevated-plus maze models also demonstrated superiority of CBZ-NLCs to CBZ dispersion. From the results, CBZ-NLCs presents a promising strategy to improve brain delivery and therapeutic outcomes of CBZ in epilepsy. [ABSTRACT FROM AUTHOR]

Silymarin (SLM) is a mixture of flavonolignans extracted from the fruit of Silybum marianum L. Gaertn. which has been used for decades as a hepatoprotector. Silymarin has recently been proposed to be beneficial in type 2 diabetic patients. Constituents of SLM are poorly water-soluble and low permeable compounds, with consequently limited oral bioavailability. This study aimed to investigate the possibility of delivery of SLM via nanostructured lipid carriers (NLCs) to overcome these issues and for preparation of an oral dosage form. NLCs were prepared through an emulsion/evaporation/solidifying method. Cetyl palmitate:Lauroglycol 90 was selected as the lipid mixture and Brij S20 as surfactant. NLCs were chemically and physically characterized. Encapsulation efficiency was more than 92%. The storage stability of the NLC suspension was also investigated and the freeze-drying process was taken into consideration. After assessing the stability of the formulation in a simulated gastrointestinal environment, the release of SLM was monitored in different pH conditions. In vitro experiments with artificial membranes (PAMPA) and Caco-2 cells revealed that the NLCs enhanced the permeation of SLM. Active processes are involved in the internalization of NLCs, as evidenced by cellular uptake studies. After preliminary toxicological studies, the formulation was studied in vivo in a streptozotocin (STZ)-induced diabetic mouse model in the presence of metabolic syndrome. The formulation was also compared to an NLC containing stearic acid:Capryol 90, to evaluate the effect of the lipid matrix on the in vivo performance of nanocarriers. Finally, hepatic histopathological analyses were also conducted. Both SLM-loaded NLCs exhibited in vivo a significant down-regulation of blood glucose and triglyceride levels better than free SLM, with a liver-protective effect. Furthermore, both formulations showed a significant anti-hyperalgesic effect on STZ-induced neuropathy. [ABSTRACT FROM AUTHOR]

The current study sought to formulate, optimize, and stabilize amphotericin B (AmB) loaded PEGylated nanostructured lipid carriers (NLC) and to study its ocular biodistribution following topical instillation. AmB loaded PEGylated NLC (AmB-PEG-NLC) were fabricated by hot-melt emulsification followed by high-pressure homogenization (HPH) technique. 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (mPEG-2K-DSPE) was used for surface PEGylation. mPEG-DSPE with different PEG molecular weight, 1 K, 2 K, 5 K, 10 K, and 20 K, were screened for formulation stability. Furthermore, the AmB loaded PEGylated (2K) NLC (AmB-PEG2K-NLC) was optimized using Box-Behnken design with respect to the amount of AmB, castor oil, mPEG-2K-DSPE, and number of high-pressure homogenization cycles as the factors; particle size, zeta potential, PDI, entrapment efficiency, and loading efficiency as responses. Stability of the optimized AmB-PEG2K-NLC was assessed over 4 weeks, at 4 °C as well as 25 °C and effect of autoclaving was also evaluated. AmB-PEG2K-NLC were tested for their in vitro antifungal activity against Candida albicans (ATCC 90028), AmB resistant Candida albicans (ATCC 200955) and Aspergillus fumigatus (ATCC 204305). Cytotoxicity of AmB-PEG2K-NLC was studied in human retinal pigmented epithelium cells. In vivo ocular biodistribution of AmB was evaluated in rabbits, following topical application of PEGylated NLCs or marketed AmB preparations. PEGylation with mPEG-2K-DSPE prevented leaching of AmB and increased the drug load significantly. The optimized formulation was prepared with a particle size of 218 ± 5 nm; 0.3 ± 0.02 PDI, 4.6 ± 0.1% w/w drug loading, and 92.7 ± 2.5% w/w entrapment efficiency. The optimized colloidal dispersions were stable for over a month, at both 4 °C and 25 °C. AmB-PEG2K-NLCs showed significantly (p < 0.05) better antifungal activity in both wild-type and AmB resistant Candida strains and, was comparable to, or better than, commercially available parenteral AmB formulations like Fungizone™ and AmBisome®. AmB-PEG2K-NLC did not show any toxicity up to a highest concentration of 1% (v/v) (percent formulation in medium). Following topical instillation, AmB was detected in all the ocular tissues tested and statistically significant (p > 0.05) difference was not observed between the formulations tested. An optimized autoclavable and effective AmB-PEG2K-NLC ophthalmic formulation with at least one-month stability, in the reconstituted state, has been developed. [ABSTRACT FROM AUTHOR]

In order to deliver Salvianolic acid B (Sal B) and Baicalin (BA) to the brain tissue to repair neuron damage and improve cerebral ischemia-reperfusion injury (IRI), in our previous study, a nanostructured lipid carrier (NLC) containing BA and Sal B, and modified by the transferrin receptor monoclonal antibody OX26 (OX26-BA/Sal B-NLC) was constructed. The present study is to evaluate its in vitro release behavior, in vitro and in vivo targeting ability, in vitro pharmacodynamics and brain pharmacokinetics. The results showed that the release mechanism of the formulation was in line with the Weibull model release equation. The in-vitro and in-vivo targeting ability study exhibited that OX26 modified formulations was obviously higher than that of non-modified and solution groups. The results of in vitro preliminary study to investigate the protective effect of OX26-BA/Sal B-NLC on oxygen-glucose deprivation/reperfusion injured cells showed that it could decrease the injury. Furthermore, the results of brain microdialysis study showed that the OX26-modified preparation group could significantly increase the content of BA in the brain. In the solution group and the unmodified group, Sal B can only be detected at few time points, while OX26-modified BA/Sal B-NLC could be detected within 4 h. These results indicating that OX26-modified NLC can promote the brain delivery of Sal B and BA combination. [ABSTRACT FROM AUTHOR]

Mupirocin is a promising broad-spectrum antibiotic that is effective in treating MRSA infections. However, due to its rapid elimination and hydrolysis following injection and high protein binding, current therapeutic use is limited to topical administration. Nanotechnology-driven innovations provide hope for patients and practitioners in overcoming the problem of drug degradation by encapsulation. The objective of this research is to develop and characterize Mupirocin-Loaded Nanostructured Lipid Carriers (M-NLC) for intravascular administration. The MNLC was produced by a combination of high shear homogenization and high pressure homogenization of solid (cetyl palmitate) and liquid (caprylic/caprylic acid) biocompatible lipids in 5 different ratios. The mean particle size, polydispersity index (PDI) and the zeta potential (ZP) of the MNLC formulations were between 99.8 and 235 nm, PDI lower than 0.164, ZP from −25.96 to −19.53 and pH ranging from 6.28–6.49. The MNLC formulation also enhances the anti-bacterial activity of mupirocin. All formulation showed sustained drug release and good physical characteristics for three months storage under 25 °C. It also revealed that the MNLC 1 is safe at 250 mg/kg dose in rats. The MNLC 1 also showed a significant increase in plasma concentration in rabbits following IV administration thus, demonstrating an enhancement on its pharmacokinetic profile as compared to free mupirocin. Unlabelled Image [ABSTRACT FROM AUTHOR]

Schematic representation of the processes for preparing PTX@FA-NLC-PEG-Ce6 and its application for tumor-targeted and light-triggered photodynamic therapy combined with chemotherapy for breast cancer. (1) PTX@FA-NLC-PEG-Ce6 accumulates in tumor site through the EPR effect. (2) PTX@FA-NLC-PEG-Ce6 is recognized by FR and then internalized into tumor cells. (3) Accompanying the disintegration of the drug-loading system in the acidic intracellular microenvironment, PTX acts on the cell cycle to exert chemotherapy and Ce6 induces the production of reactive oxygen species to exert PDT under the illumination of red light at a specific wavelength. Breast cancer remains a major threat to women's health, and the incidence of breast cancer continues to increase each year. Paclitaxel (PTX) is commonly used to treat breast cancer, but shows limited solubility and is associated with major side effects, limiting its clinical applications. Photodynamic therapy (PDT) is a promising treatment for breast cancer but is limited by the poor solubility of photosensitizers and difficulties in targeting and enriching the tumor tissue with photosensitizers. Here, we prepared a new nanocarrier system using nanostructured lipid carriers (PTX@FA-NLC-PEG-Ce6) harboring PTX, chlorin e6 (Ce6), and folic acid-targeted head to overcome the limitations of PTX and Ce6 in hydrophobicity and increase the target efficiency of chemotherapy drugs and photosensitizers at the tumor. The results showed that the drug-loading system met the requirements for intravenous injection, had tumor targeting ability, and could be easily taken up by MDA-MB-231 cells. Moreover, Ce6 could be dissociated from the surface of the drug-loading system and evenly distributed in cells after a period of time when the nanostructured lipid carriers had entered lysosomes through endocytosis. Additionally, reactive oxygen species were then produced to induce PDT at a specific wavelength of illumination. In vitro pharmacodynamic experiments showed that combined PDT and chemotherapy had synergistic effects (combination index: 0.647). Furthermore, pharmacodynamic experiments in nude mice showed that the drug-loading system had ideal antitumor effects without obvious side effects. Thus, PTX@FA-NLC-PEG-Ce6 may have applications as a promising drug-loading system for PDT combined with chemotherapy in patients with breast cancer. [ABSTRACT FROM AUTHOR]

This study compared the in vitro and in vivo effects of different aliphatic acid grafted N -trimethyl chitosan (TMC) surface-modified nanostructured lipid carriers (NLC) by oral delivery. Medium-chain fatty acids, decylic acids (DA), and long-chain fatty acids, palmitic acids (PA) were selected as contrasting objects. TMC, DA grafted TMC (DA-TMC), and PA grafted TMC (PA-TMC) were successively synthesized. Kaempferol loaded NLC (KNLC), KNLC coated with DA-TMC (DA-TMC-KNLC) and PA-TMC (PA-TMC-KNLC) were fabricated, respectively. KNLC were subspherical in shape at nano-size limits. The particle size increased from 93.6 to 125.5 nm and the zeta potential changed from negative to positive due to surface-modification. The KNLC surface-modified with different aliphatic acid grafted TMC displayed a diverse release profiles at the simulative physiological environment, which contrasted that of KNLC. Pharmacokinetic studies demonstrated that the nanoparticles all could improve the AUC values and prolong blood retention times compared to that of kaempferol suspensions. Cell uptake and in situ intestinal perfusion experiments revealed that DA-TMC-KNLC and PA-TMC-KNLC could remarkably enhance cellular uptake of kaempferol into Caco-2 cells and drug absorption in each intestinal segment in comparison with KNLC, repectively. Wherein, DA-TMC-KNLC exhibits the greatest uptake and absorption efficiency as compared to kaempferol suspensions, KNLC and PA-TMC-KNLC. Collectively, DA-TMC surface-modified NLC might serve as a potential drug carrier for oral delivery of water-insoluble flavonoid ingredients. [ABSTRACT FROM AUTHOR]

Fucoxanthin (FUCO) is a marine carotenoid characterized by antiproliferative properties against hyperproliferative cells. The aim of this work was to design and develop nanostructured lipidic carriers (NLCs) based on bacuri butter and tucumã oil and loaded with FUCO, intended for skin application to prevent skin hyperproliferative diseases and in particular psoriasis. The presence of FUCO should control the hyperproliferation of skin diseased cells and the lipids forming the NLC core, rich in antioxidants and characterized by wound healing properties, should favor the restoring of skin integrity. NLCs were coated with chitosan (CS) to improve their biopharmaceutical properties (bio/mucoadhesion and wound healing) and to combine the advantages of lipidic nanoparticles with the biological properties of CS. Chitosan coated and non-coated NLC were prepared by means of high shear homogenization and characterized for chemico-physical and biopharmaceutical properties (in vitro biocompatibility and cell uptake towards normal dermal human fibroblasts). Moreover, the pharmacological activity of FUCO loaded in NLCs was assessed in psoriatic-like cellular model. NLCs were characterized by dimensions ranging from about 250 to 400 nm. Moreover, the CS coating and FUCO loading determined an increase of size. Moreover, TEM and zeta potential analysis confirmed the presence of CS coating on nanoparticle surface, thus conferring to nanoparticle good bioadhesion properties. NLCs uptake in fibroblasts was observed and NLC-FUCO-CS caused a reduction of cell viability with a less marked effect in fibroblasts rather than in psoriatic cells, highlighting the capability of this system to control skin hyperproliferation and inflammation. The loading of NLC-FUCO-CS in pullulan film should render NLCs application easy, without impair prompt interaction of the drug with the skin. Considering the overall results skin application of CS coated NLCs loaded with FUCO seems a promising approach to control skin hyperproliferation and to preserve skin integrity in psoriatic skin. [ABSTRACT FROM AUTHOR]