Toward a Platform for the Treatment of Burns: An Assessment of Nanoemulsions vs. Nanostructured Lipid Carriers Loaded with Curcumin.

Curcumin is a highly promising substance for treating burns, owing to its anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. However, its therapeutic use is restricted due to its hydrophobic nature and low bioavailability. This study was conducted to address these limitations; it developed and tested two types of lipid nanocarriers, namely nanoemulsions (NE-CUR) and nanostructured lipid carriers (NLC-CUR) loaded with curcumin, and aimed to identify the most suitable nanocarrier for skin burn treatment. The study evaluated various parameters, including physicochemical characteristics, stability, encapsulation efficiency, release, skin permeation, retention, cell viability, and antimicrobial activity. The results showed that both nanocarriers showed adequate size (~200 nm), polydispersity index (~0.25), and zeta potential (~>-20 mV). They also showed good encapsulation efficiency (>90%) and remained stable for 120 days at different temperatures. In the release test, NE-CUR and NCL-CUR released 57.14% and 51.64% of curcumin, respectively, in 72 h. NE-CUR demonstrated better cutaneous permeation/retention in intact or scalded skin epidermis and dermis than NLC-CUR. The cell viability test showed no toxicity after treatment with NE-CUR and NLC-CUR up to 125 µg/mL. Regarding microbial activity assays, free curcumin has activity against P. aeruginosa, reducing bacterial growth by 75% in 3 h. NE-CUR inhibited bacterial growth by 65% after 24 h, and the association with gentamicin had favorable results, while NLC-CUR showed a lower inhibition. The results demonstrated that NE-CUR is probably the most promising nanocarrier for treating burns.

Copaifera langsdorffii Oleoresin-Loaded Nanostructured Lipid Carrier Emulgel Improves Cutaneous Healing by Anti-Inflammatory and Re-Epithelialization Mechanisms.

The skin is essential to the integrity of the organism. The disruption of this organ promotes a wound, and the organism starts the healing to reconstruct the skin. Copaifera langsdorffii is a tree used in folk medicine to treat skin affections, with antioxidant and anti-inflammatory properties. In our study, the oleoresin of the plant was associated with nanostructured lipid carriers, aiming to evaluate the healing potential of this formulation and compare the treatment with reference drugs used in wound healing. Male Wistar rats were used to perform the excision wound model, with the macroscopic analysis of wound retraction. Skin samples were used in histological, immunohistochemical, and biochemical analyses. The results showed the wound retraction in the oleoresin-treated group, mediated by α-smooth muscle actin (α-SMA). Biochemical assays revealed the anti-inflammatory mechanism of the oleoresin-treated group, increasing interleukin-10 (IL-10) concentration and decreasing pro-inflammatory cytokines. Histopathological and immunohistochemical results showed the improvement of re-epithelialization and tissue remodeling in the Copaifera langsdorffii group, with an increase in laminin-γ2, a decrease in desmoglein-3 and an increase in collagen remodeling. These findings indicate the wound healing potential of nanostructured lipid carriers associated with Copaifera langsdorffii oleoresin in skin wounds, which can be helpful as a future alternative treatment for skin wounds.

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

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

Development, optimization, and evaluation of a nanostructured lipid carrier of sesame oil loaded with miconazole for the treatment of oral candidiasis.

Candida albicans is the fungus responsible for oral candidiasis, a prevalent disease. The development of antifungal-based delivery systems has always been a major challenge for researchers. This study was designed to develop a nanostructured lipid carrier (NLC) of sesame oil (SO) loaded with miconazole (MZ) that could overcome the solubility problems of MZ and enhance its antifungal activity against oral candidiasis. In the formulation of this study, SO was used as a component of a liquid lipid that showed an improved antifungal effect of MZ. An optimized MZ-loaded NLC of SO (MZ-SO NLC) was used, based on a central composite design-based experimental design; the particle size, dissolution efficiency, and inhibition zone against oral candidiasis were chosen as dependent variables. A software analysis provided an optimized MZ-SO NLC with a particle size of 92 nm, dissolution efficiency of 88%, and inhibition zone of 29 mm. Concurrently, the ex vivo permeation rate of the sheep buccal mucosa was shown to be significantly (p < .05) higher for MZ-SO NLC (1472 µg/cm2) as compared with a marketed MZ formulation (1215 µg/cm2) and an aqueous MZ suspension (470 µg/cm2). Additionally, an in vivo efficacy study in terms of the ulcer index against C. albicans found a superior result for the optimized MZ-SO NLC (0.5 ± 0.50) in a treated group of animals. Hence, it can be concluded that MZ, through an optimized NLC of SO, can treat candidiasis effectively by inhibiting the growth of C. albicans.

Assessment of a Novel Vitamin D3 Formulation with Nanostructured Lipid Carriers for Transdermal Delivery.

OBJECTIVE: Develop and assess a transdermal emulsion loaded with nanostructured lipid carriers for vitamin D3 supplementation. METHODS: Vitamin D3 loaded nanostructured lipid carriers, produced via high shear homogenization and ultrasonication, were assessed for their particle size, distribution, morphology, zeta potential, entrapment efficiency, and cytotoxicity. They were incorporated into a transdermal vehicle, and the stability and ex vivo permeation were evaluated. RESULTS: Spherical nanoparticles were developed with a particle size of 192.5 nm, a polydispersity index of 0.13, a zeta potential of -29.0 mV, and an entrapment efficiency of 99.75%. They were stable (particle size and distribution) for 15 days when stored in a refrigerator, and for 30 days at room temperature and 32°C. The nanoparticles decreased the drug cytotoxicity against fibroblasts, as shown by IC50 (nanoparticle: 32.48 µg mL-1 vitamin D3: 16.73 µg mL-1). The emulsion loaded with nanoparticles minimized the degradation of vitamin D3 when compared with the nanoparticle dispersion. Additionally, the emulsion provided the skin permeation of vitamin D3 following the recommended daily allowance. CONCLUSION: To the best of our knowledge, this is the first study to use nanostructured lipid carriers for transdermal delivery of vitamin D. The developed formulation is a promising strategy to overcome the vitamin D3 variable oral bioavailability. It also represents a comfortable route of administration; thus it could be beneficial for patients and clinicians. However, further studies are needed to allow the permeation of larger amounts of vitamin D3, and the combination of these nanoparticles with microneedles would be interesting.

Resveratrol: Isolation, and Its Nanostructured Lipid Carriers, Inhibits Cell Proliferation, Induces Cell Apoptosis in Certain Human Cell Lines Carcinoma and Exerts Protective Effect Against Paraquat-Induced Hepatotoxicity.

Resveratrol (RES) (trans-3, 5,-4'-trihydroxystilebene) is a multi-biofunctional compound found in a variety of plants such as grapes and mulberries. Studies of nanoencapsulated resveratrol have indicated that this compound can inhibit the growth of cancer cells and free radicals. The aim of this study was to isolate resveratrol from Vitis vinifera, develop and evaluate resveratrol nanostructured lipid carriers (NLCs) and/or resveratrol encapsulated chitosan-coated nanostructured lipid carriers (CSNLCs) using low-viscous chitosan for anticancer therapy. In addition, our study was carried out to examine the prophylactic potential of RES, NLC, and CSNLC on paraquat-induced injury in rat hepatocytes. In this study we isolated resveratrol and encapsulated NLCs in phosphate-buffered saline solution using a phase inversion method. In addition, CSNLCs were prepared by ionic gelation method of NLCs using chitosan. NLCs and CSNLCs were then characterized for their particle size, zeta potential, morphology, and entrapment efficiency. Furthermore, NLCs and CSNLCs were evaluated for their cytotoxic effect on Hep-G2, human HCT-116 (colorectal cancer cell line), lymphoblastic leukemia (1301), and human MCF-7 (Michigan Cancer Foundation-7) cells as well as their effect on caspase-3 and death receptor (DR-4). In addition, incubation of hepatocytes with paraquat resulted in increased formation of TBARS (thiobarbituric acid reactive substances) with a parallel increase in lactate dehydrogenase (LDH) leakage at 1 h after incubation. Time-dependent depletion of cellular glutathione (GSH) was observed starting 2 h after incubation with paraquat. The mean particle size of NLC and CSNLC were 67.0 and 98.41 nm, zeta potential were (-) 24.8 and (+) 31.6 mV, entrapment efficiency were 74.15% and 85.46%, respectively, with the observed shapes of nanoparticle being spherical. The treatment of Hep-G2, human HCT-116, lymphoblastic leukemia (1301), and human MCF-7 cells with NLC led to high inhibition in the cell proliferation as concluded by the low IC50 values 27.7, 17.43, 35.39, and 47.66 µg/mL, respectively, whereas CSNLC had high cytotoxic effect on Hep-G2, human HCT-116, lymphoblastic leukemia (1301), and human MCF-7 cells with low IC50 values 13.29, 10.56, 16.79 and 22.60 µg/mL, respectively. Both NLC and CSNLC possess apoptotic properties through activation of the caspase-3 and death receptor (DR-4). In addition, incubation of hepatocytes with RES, NLC, and CSNLC markedly protected against paraquat-induced formation of TBARS, increase in LDH leakage, and prevented GSH depletion. The most effective doses for ethyl acetate, ethanolic, and aqueous extracts were 7.5, 10, and 12.5 µg, respectively. The results presented here may suggest that nanoencapsulated resveratrol isolated from the stems of V. vinifera to obtain NLC and CSNLC possess anticancer and apoptotic effects on cell proliferation, and therefore, can be used as new approach of pharmaceutical drugs. In addition, the results clearly suggest that the RES, NLC, and CSNLC exerted protective effect against cytotoxicity induced by paraquat. On the contrary, the effect decreased in order of CSNLC, NLC, and RES.

Nanostructured lipid carrier-based smart gel: a delivery platform for intra-articular therapeutics.

The promising potential of nano-structured lipid carrier (NLC) polymeric gel of CUR as an effective treatment for rheumatoid arthritis by intra-articular route of administration was investigated. NLC composed of cetylpalmitate, Labrafac PG & Captex 200, Tween 80 and Labrasol. The hot homogenization method employed by melt ultrasonication was used. The formulated NLC dispersions were characterized and were suitably dispersed into the matrix of pluronic F-127(PLF-127) and pluronic F-68 (PLF-68). A two-factor three-level full factorial design was employed to deduce the optimal concentrations of PLF-127 and PLF-68. The optimized formulations were sterilized by gamma radiation. The formulated NLC smart gels were characterized and evaluated for various parameters. The efficacy evaluation by antigen-induced monoarthritis model and biocompatibility testing by histopathological studies was performed. Formulated NLCs exhibited an average particle size of 165.12 nm, entrapment efficiency of 72.15%, and zeta potential of -21.67 mV. The optimized CUR-NLC smart gel was demonstrated to have a sol-gel transformation at 33.21 °C and 94.32% drug release at 84 h. NLC's which were sterile and easily syringeable, continued to remain within the colloidal range. CUR-NLC smart gels were found to be biocompatible and showed a significant reduction in rat knee joint inflammation compared to free drug.

[Effect of ginsenoside Rg_3 nanostructured lipid carrier modified by pullulan on promoting absorption and its anti-tumor evaluation in vitro].

Ginsenoside Rg_3 is widely used in clinical practice as an anti-tumor adjuvant drug, but its application is limited due to its poor oral absorption. In this study, we intended to construct a ginsenoside Rg_3 nanostructured lipid carrier modified by the pullulan(PUL-Rg_3-NLC) to improve the adhesion properties of ginsenoside Rg_3, promote the drug uptake and improve the anti-tumor efficacy. PUL-Rg_3-NLC was characterized by morphology, particle size and Zeta potential. In vivo adhesion characteristics were evaluated by oral gavage tests, and the results were verified from multiple perspectives in combination with in vitro uptake behavior and in vitro pharmacodynamics. The results showed that PUL-Rg_3-NLC, with a particle size of(102±1.89) nm, was characterized by gastric adhesion and could be retained in gastric tissues for a long time, and its uptake by BGC-823 cells was promoted mainly through the pathway mediated by the caveolin-mediated endocytosis. In vitro MTT, cell apoptosis, wound-healing assay and invasion assay all showed some anti-tumor effects. Therefore, PUL-Rg_3-NLC can significantly promote the adhesion of Rg_3 in the stomach, promote the uptake of drugs by gastric cancer cells, and improve the anti-tumor effect. This study can provide some reference for the adjuvant treatment of gastric cancer.

Quality by Design Approach for Preparation of Zolmitriptan/Chitosan Nanostructured Lipid Carrier Particles - Formulation and Pharmacodynamic Assessment.

PURPOSE: Zolmitriptan (ZT) is a selective serotonin agonist that is used for the treatment of migraine. It belongs to BCS class III with high solubility and low permeability. Besides, the drug is subjected to pre-systemic metabolism. Accordingly, new Zolmitriptan/chitosan nanostructured lipid carriers (ZT/CT NLCs) coated with Tween 80 (stealthy layer) have been developed to overcome such demerits. METHODS: The NLCs were developed by combining ultrasonication and double emulsion (w/o/w) techniques. The lipids were Gelucire and Labrasol. Herein, the quality by design (23 full factorial design) was scrupulously followed, where critical process parameters and critical quality attributes were predefined. The optimized formulation (F8) was fully characterized with respect to entrapment efficiency (%EE), percentage yield (% yield), particle size, size distribution (PDI), zeta potential (ZP), morphological appearance (TEM). In vitro release, stability study and pharmacodynamic evaluations were also assessed. The optimized freeze dried formula was dispensed in in situ gelling hard gelatin capsule encompassing pectin and guar gum for further in vitro and pharmacodynamic evaluations. RESULTS: The optimized spherical nanoparticles experienced high percentage EE and yield (78.14% and 60.19%, respectively), low particle size and PDI (343.87 nm and 0.209, respectively), as well as high negative ZP (-25.5 mV). It showed good physical stability at refrigerated conditions. The NLCs dispensed in in situ gelling hard gelatin capsule comprising pectin and guar gum experienced sustained release for 30 h and significantly maintained the pharmacological effect in mice up to 8 h (p < 0.001). CONCLUSION: ZT, a BCS class III drug that suffers from poor permeability and pre-systemic metabolism, was successfully maneuvered as nanostructured lipid carrier particles (NLCs). The incorporation of the NLCs in in situ gelling hard gelatin capsules fulfilled a dual function in increasing permeability, as well as sustaining the pharmacodynamic effect. This result would open new vistas in improving the efficacy of other class III drugs.

Natural, Synthetic and their Combinatorial Nanocarriers Based Drug Delivery System in the Treatment Paradigm for Wound Healing Via Dermal Targeting.

A wound refers to the epithelial loss, accompanied by loss of muscle fibers collagen, nerves and bone instigated by surgery, trauma, frictions or by heat. Process of wound healing is a compounded activity of recovering the functional integrity of the damaged tissues. This process is mediated by various cytokines and growth factors usually liberated at the wound site. A plethora of herbal and synthetic drugs, as well as photodynamic therapy, is available to facilitate the process of wound healing. Generally, the systems used for the management of wounds tend to act through covering the ruptured site, reduce pain, inflammation, and prevent the invasion and growth of microorganisms. The available systems are, though, enough to meet these requirements, but the involvement of nanotechnology can ameliorate the performance of these protective coverings. In recent years, nano-based formulations have gained immense popularity among researchers for the wound healing process due to the enhanced benefits they offer over the conventional preparations. Hereupon, this review aims to cover the entire roadmap of wound healing, beginning from the molecular factors involved in the process, the various synthetic and herbal agents, and combination therapy available for the treatment and the current nano-based systems available for delivery through the topical route for wound healing.

Formulation, Preparation and Evaluation of Nanostructured Lipid Carrier Containing Naringin and Coix Seed Oil for Anti-Tumor Application Based on "Unification of Medicines and Excipients".

BACKGROUND: "Unification of medicines and excipients" is the special principle which means fatty oil with pharmacodynamic activity derived from traditional Chinese medicine are taken as liquid lipids in perparation for dual-drug delivery,  which improve the treatment effect and reduce unnecessary excipients. PURPOSE: The aim of this study was to prepare a nanostructured lipid carrier (NLC) with naringin (NG) containing coix seed oil (CSO) as liquid lipid based on the theory (NCNLC) in order to achieve synergistic antitumor activity against hepatocellular carcinoma. METHODS: We developed NCNLCs using ultrasonic melt-emulsification method. The antitumor effect in vivo/in vitro and drug release ability were compared to NLC prepared with conventional liquid lipids: neodecanoate triglycerides (NDNLC) and oleic acid (NONLC). RESULTS: Transmission electron microscopy showed that NCNLCs had a well-defined spherical shape, small size, and narrow polydispersity index. Importantly, the release of drugs from NDNLCs and NONLCs was slower than NCNLCs. In the cell study, the result showed a significantly greater antiproliferative effect towards HepG2 cells, and the half-maximal inhibitory concentration of NCNLCs was 3.24-fold, 1.70-fold and 1.52-fold lower to that of free drug, NDNLCs and NONLCs, respectively. Moreover, NCNLCs significantly induced HepG2 cells apoptosis by being 2.12-fold and 9.28-fold higher to that of NDNLCs and NONLCs, respectively. In the study of antitumor efficacy in vivo, the synergistic effect of NCNLCs formulation showed markedly enhanced antitumor efficacy in a xenograft model of liver cancer. CONCLUSION: The advantages of "unification of medicines and excipients" in formulation characters, drug release and synergistic antitumor effect provide a new idea for the application of the fatty oil of traditional Chinese medicine in the nano-drug delivery for cancer therapy.

A new medium-throughput screening design approach for the development of hydroxymethylnitrofurazone (NFOH) nanostructured lipid carrier for treating leishmaniasis.

Hydroxymethilnitrofurazone (NFOH) is a nitrofurazone derivative and has potential use in treating leishmaniasis. However, due to low water solubility and bioavailability, NFOH has failed in in vivo tests. Nanostructured lipid carrier (NLC) is an alternative to overcome these limitations by improving pharmacokinetics and modifying drug delivery. This work is focused on developing a novel NFOH-loaded NLC (NLC-NFOH) using a D-optimal mixture statistical design and high-pressure homogenization, for oral administration to treat leishmaniasis. The optimized NLC-NFOH consisted of Mygliol® 840, Gelucire® 50/13, and Precirol® ATO 5 as lipids. These lipids were selected using a rapid methodology Technobis Crystal 16 T M, microscopy, and DSC. Different tools for selecting lipids provided relevant scientific knowledge for the development of the NLC. NLC-NFOH presented a z-average of 198.6 ±â€¯5.4 nm, PDI of 0.11 ±â€¯0.01, and zeta potential of -13.7 ±â€¯0.7 mV. A preliminary in vivo assay was performed by oral administration of NLC-NFOH (2.8 mg/kg) in one healthy male Wistar rat (341 g) by gavage. Blood from the carotid vein was collected, and the sample was analyzed by HPLC. The plasma concentration of NFOH after 5 h of oral administration was 0.22 µg/mL. This same concentration was previously found using free NFOH in the DMSO solution (200 mg/kg), which is an almost 100-fold higher dose. This study allowed a design space development approach of the first NLC-NFOH with the potential to treat leishmaniasis orally.

Fabrication and characterization of nanostructured lipid carriers (NLC) using a plant-based emulsifier: Quillaja saponin.

Nanostructured lipid carriers (NLCs) are a type of colloidal delivery system that was developed in the pharmaceutical industry to combine the advantages and eliminate the shortcomings of oil-in-water (O/W) nanoemulsions and solid lipid nanoparticles (SLNs). The hydrophobic core of the particles within NLCs consists of a solidified fat phase with a partially disorganized structure, which inhibits morphological changes and bioactive expulsion. In the present study, we formulated NLCs using a hot-homogenization approach using fully hydrogenated soybean oil (HSO) as the lipid phase and quillaja saponins as a natural surfactant. The NLCs formed had a low viscosity and milky white appearance similar to that of O/W nanoemulsions. The fabrication conditions were optimized, including the number of passes through the microfluidizer, stirring conditions, cooling rate, and emulsifier level. Unlike bulk HSO, the emulsified form had to be supercooled substantially to promote crystallization of the lipid droplets, which was attributed to differences in nucleation behavior. The crystallization temperature decreased with increasing saponin concentration, which was probably because smaller droplets were formed at higher emulsifier levels. For instance, at 3, 6, 9, and 12 wt% saponin, the degree of supercooling was 10, 15, 18, and 18 °C, while the mean particle diameter was 0.82, 0.53, 0.41, and 0.44 µm, respectively. The melting and crystallization behavior of the NLCs was characterized using an optical microscope and differential scanning calorimetry (DSC), while the morphology of the NLCs was characterized using transmission electron microscopy (TEM). This analysis showed that the NLCs contained spherical particles with a crystallization temperature around 31 °C. This information may be useful for formulating NLC from natural ingredients for application in the food and beverage industry.

Curcumin-Loaded Nanostructured Lipid Carrier Modified with Partially Hydrolyzed Ginsenoside.

The objective of the present study was to investigate the effect of partially hydrolyzed ginsenoside on the physicochemical properties and in vitro release of curcumin from phospholipid-based nanostructured lipid carrier (NLC). NLC formulas modified with partially hydrolyzed ginsenoside (NLC-PG) were prepared with different amounts of ginsenoside using the conventional hot-melt method. The average particle size of curcumin-loaded NLC-PG ranged from 150 to 200 nm, and polydispersity index was in the range of 0.101-0.177, indicating monodispersed particle size distribution. Optical microscopy showed no sedimentation or recrystallization of curcumin even at 10,000 µg/ml concentration as NLC-PG in distilled water, indicating significantly enhanced solubility. TEM image showed that the nanoparticles were monodispersed with a multilayered core/shell structure. X-ray diffraction and FTIR spectroscopy showed that curcumin was amorphous in the NLC-PG, and there was no interaction between curcumin and the excipients. In vitro release study using simulated gastric/intestinal fluid media revealed that the release rate (Jss) of curcumin from the NLC-PG increased as a function of the ginsenoside content in the lipid carrier. Moreover, the Jss of curcumin kept gradually increasing in the presence of lipase, whereas in the presence of viscozyme, it sharply increased until the ginsenoside content reached 9.09% and subsequently plateaued. Partially hydrolyzed ginsenoside increased the Jss of curcumin from curcumin-loaded NLC-PG and therefore may be useful for improving the bioavailability of curcumin.

Silymarin-loaded nanostructured lipid carrier gel for the treatment of skin cancer.

Aim: The present study was aimed at determining the antiproliferative, antioxidant, anti-inflammatory and antitumor activity of developed silymarin-nanostructured lipid carrier (NLC) gel. Materials & methods: B16 melanoma cell line and albino mice were used as ex vivo and in vivo models, respectively, to evaluate the aforementioned pharmacological activities. Results: The volume of large tumors significantly (p < 0.05) reduced from 5.02 to 3.05 mm3, levels of IL-1α and TNF-α were significantly (p < 0.001) lower and levels of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) significantly (p < 0.0001) increased in the group treated with silymarin-NLC gel. Furthermore, in skin treated with placebo and conventional gels, a basosquamous carcinoma and squamous cell carcinoma were noticed, respectively. Conclusion: Silymarin-NLC gel presented better treatment outcomes compared with silymarin-conventional gel.

Nanostructured Lipid Carrier of Propofol: a Promising Alternative to Marketed Soybean Oil-Based Nanoemulsion.

Nanostructured lipid carrier (NLC) of propofol was formulated using hot emulsification-probe sonication method for improvising its parenteral delivery by reducing pain on injection and risk of microbial contamination. The formulated NLC was optimized using central composite design and evaluated for particle size, zeta potential, morphology, free propofol concentration, hemocompatibility, stability, pain on injection, in vivo anesthetic activity, pharmacokinetics, and antimicrobial effectiveness in comparison to the marketed formulation. Optimized NLCs exhibited globule size, less than 200 nm, and zeta potential - 24.1 mV, indicating its stability. TEM images confirmed the spherical shape and nanosize (200 nm) of optimized NLCs. Free propofol concentration was also found to be 40% lesser than marketed formulation. Optimized NLC was found to be non-hemolytic. Rat paw-lick study showed that propofol NLC was significantly less painful compared to the marketed formulation. Anesthetic potential and pharmacokinetics of optimized NLCs were found to be similar to that of the marketed formulation. NLC was found stable in long-term storage under room temperature. Antimicrobial effectiveness study showed that propofol NLC suppressed microbial growth to a greater extent as compared to the marketed formulation. Hence, the developed propofol NLCs appeared to be clinically useful as a potential carrier for propofol delivery.

Improved Stability of Polyglycerol Polyricinoleate-Substituted Nanostructured Lipid Carrier Cholecalciferol Emulsions with Different Carrier Oils.

Cholecalciferol, also known as vitamin D3 , is a recognized therapeutic agent for treatment of bone diseases and cancer. However, instability and poor bioavailability have been major challenges for delivering Vitamin D3 . The objective of this study was to formulate improved nanostructured lipid carrier (NLC) vitamin D3 emulsions. We tested the effect of different carrier oils and the use of a solid lipid nanoparticle emulsifier, polyglycerol polyricinoleate (PGPR) on the stability of the vitamin D3 emulsions. In contrast to the control that used glyceryl monostearate (GMS) the PGPR substitution resulted in relatively small particle sizes (0.30 to 0.43 µm), with high absolute value of zeta potentials (39.5 to 67.8 mV) and high encapsulation efficiency (85.2% to 90.4%). The stability of the NLC emulsions against environmental stresses was evaluated under varying conditions of ionic strength, pH, freeze-thaw cycles, and storage at different temperatures. Although NLC emulsions were stable at high ionic strengths, they were found to be unstable at low pH (<3), which led to aggregation and coalescence of emulsion droplets. In case of freeze-thaw stress, although relatively stable compared to control NLC, the PGPR substituted groups exhibited a slight increase in particle size and a decrease in zeta potential when the cycle was repeated five times. Additionally, we found that PGPR-substituted emulsions showed higher liquid dispersion stability than controls at 25 and 65 °C. Thus, we have formulated a modified NLC vitamin D3 emulsion that can be widely used in the food industry. PRACTICAL APPLICATION: Vitamin D3 , an essential micronutrient, is often added as supplements in food products and beverages for added health benefits. However, the stability of vitamin D3 emulsions that are used in the preparation of such products has been a major concern. We have developed a modified emulsion that has improved stability against environmental stresses. We believe, in future, this formulation can be efficiently used in the food industry.

[Construction of artesunate nanoparticles modified by hyaluronic acid and cell-penetrating peptides and its inhibitory effect on cancer cells in vitro].

Hyaluronic acid (HA) and cell-penetrating peptide (CPP) R6H4-SA modified artesunate nanostructured lipid carrier (HA-R6H4-NLC/ART) for anti-tumor therapy was prepared. The physicochemical properties and in vitro drug release of HA-R6H4-NLC/ART were evaluated, and the uptake and cytotoxicity of liver cancer HepG2 cells were studied. The results showed that HA-R6H4-NLC/ART was spherical like in appearance, and the average particle size was about 160 nm. In vitro release experiments showed that the drug delivery system had sustained release characteristics. Cell results showed that, in slightly acidic environment, pH sensitive CPP R6H4-SA mediated cellular uptake of nanoparticles was significantly higher than that of non-sensitive peptide R8-SA. Meanwhile, HA-R6H4-NLC/ART had a targeting effect on HepG2 cells, and the HA receptor saturation experiment showed that the endocytosis of HA-R6H4-NLC/ART was mediated by the HA receptor on the cell surface. As compared with the unmodified or R6H4-SA single modified group, HA and R6H4-SA co-modified HA-R6H4-NLC/ART significantly improved the cell uptake and had a stronger anti-tumor effect under the conditions of the slightly acid environment and hyaluronidase degradation. The above results showed that hyaluronic acid and CPP R6H4-SA co-modified artesunate nanostructured lipid carrier, which can effectively identify and penetrate the tumor cell membrane into the cell, is a potentially efficient targeting delivery system for anti-tumor drugs.

Therapeutic effect of vitamin D3-containing nanostructured lipid carriers on inflammatory bowel disease.

The active form of vitamin D3, 1,25(OH)2D3 has been found to exert multiple effects on the suppression of progression of inflammatory bowel disease (IBD). Vitamin D3 has been gathering attention as a therapy for IBD. However, the clinical trials conducted to date revealed that a relatively high dosage of vitamin D3 was required to see a significant therapeutic effect. Thus, effective formulation and delivery of vitamin D3 to colonic inflammatory lesions will be required. Herein we describe the preparation of a nanostructured lipid carrier (NLC) for the encapsulation of 1,25(OH)2D3 for colonic delivery via oral administration. The optimized fabrication procedure enabled the incorporation of 1,25(OH)2D3 in the NLC by minimizing the destruction of chemically unstable 1,25(OH)2D3. The obtained NLCs orally delivered 1,25(OH)2D3 to the colon in mice and maintained a high concentration of 1,25(OH)2D3 in the colonic tissue for at least 12 h. The NLC showed multiple effects on the suppression of symptoms of colitis induced by dextran sodium sulfate, namely maintaining crypt structure, reducing the tissue concentration of inflammatory cytokines, suppressing the infiltration of polymorphonuclear leukocytes, and augmenting anti-inflammatory CX3CR1high macrophages. Our NLCs containing 1,25(OH)2D3 may be an alternative treatment for IBD therapy.

Enhanced oral bioavailability of an antipsychotic drug through nanostructured lipid carriers.

Olanzapine is an atypical antipsychotic, undergoes extensive first pass metabolism, also has poor aqueous solubility and belongs to BCS (Biopharmaceutical Classification System) Class II drug) exhibit low oral bioavailability. To overcome this and to enhance the bioavailability, intestinal lymphatic transport of drugs can be exploited through Nano structured lipid carriers (NLCs). The NLCs were formulated by solvent diffusion method using solid lipid (glyceryl tripalmitate), liquid lipid (castor oil) and surfactants (Pluronic F-68, Soylecithin). The formulated NLCs were characterized for physico-chemical properties, in-vitro release studies and in-vivo oral bioavailability. F6 has shown average particle size of 158.5 nm with PI of 0.115 indicating narrow particle size distribution and follows uni modal distribution. It was found that the batch with stearyl amine has a zeta potential of 28.39 mV which confers stability to the dispersion. Bioavailability studies indicate that there was more than 5½-fold increase in oral bioavailability in case of NLCs (F6) compared to olanzapine suspension which indicates that NLCs provided sustained release of the drugs, and these systems can be the preferred as drug carriers for lipophilic drugs in long term disease conditions such as schizophrenia for enhanced bioavailability.