An Innovative Formulation Based on Nanostructured Lipid Carriers for Imatinib Delivery: Pre-Formulation, Cellular Uptake and Cytotoxicity Studies

Imatinib (IMT) is a tyrosine kinase enzyme inhibitor and extensively used for the treatment of gastrointestinal stromal tumors (GISTs). A nanostructured lipid carrier system (NLCS) containing IMT was developed by using emulsification–sonication methods. The characterization of the developed formulation was performed in terms of its particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, loading capacity, sterility, syringeability, stability, in vitro release kinetics with mathematical models, cellular uptake studies with flow cytometry, fluorescence microscopy and cytotoxicity for CRL-1739 cells. The particle size, PDI, loading capacity and zeta potential of selected NLCS (F16-IMT) were found to be 96.63 ± 1.87 nm, 0.27 ± 0.15, 96.49 ± 1.46% and −32.7 ± 2.48 mV, respectively. F16-IMT was found to be stable, thermodynamic, sterile and syringeable through an 18 gauze needle. The formulation revealed a Korsmeyer–Peppas drug release model of 53% at 8 h, above 90% of cell viability, 23.61 µM of IC50 and induction of apoptosis in CRL-1739 cell lines. In the future, F16-IMT can be employed to treat GISTs. A small amount of IMT loaded into the NLCSs will be better than IMT alone for therapy for GISTs. Consequently, F16-IMT could prove to be useful for effective GIST treatment.

Application of Box Behnken Design and Response Surface Methodology for Optimization Sonication Conditions of Nanostructured Lipid Carrier from Mixtures of Palm Stearin and Palm Olein

The study aimed to determine the optimum conditions of the sonication in the manufacture of nanostructured lipid carriers (NLC). Nanostructured lipid carriers were developed using a mixture of palm stearin and palm olein, water, and tween as surfactants. Optimization was carried out to obtain nanostructured lipid carriers with a size below 200nm, zeta potential + 30 mV, and polydispersity index below 0.5. Optimization of NLC using response surface methodology and Box-Behnken experimental design. The independent variables were amplitude (A, kHz), pulse on pulse off (B, minute), and time of sonication (C, minute) each at three levels, while dependent variables were zeta potential (Y1, mV), particle size (Y2, nm), and polydispersity index (Y3). Measurement for dependent variables using the Zetasizer Nano ZS particle size analyzer utilized with Malvern software (Malvern, UK). The optimum formulation was obtained at a combination of amplitude (35 kHz), pulse on pulse off (pulse on 9 pulses off 3), and time of sonication (3 minutes 25 seconds ). This resulted in NLC having particle size 127.9 nm, polydispersity index 0.191, the zeta potential of -27.3 mV.

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

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

Nano-Structured Lipid Carrier-Based Oral Glutathione Formulation Mediates Renoprotection against Cyclophosphamide-Induced Nephrotoxicity, and Improves Oral Bioavailability of Glutathione Confirmed through RP-HPLC Micellar Liquid Chromatography

The study aimed to develop a new glutathione (GSH) oral formulation to enhance the delivery of GSH and counter the nephrotoxicity of the anticancer drug, cyclophosphamide (CP). A nanostructured lipid carrier glutathione formulation (GSH-NLCs) composed of glutathione (500 mg), stearic and oleic acid (300 mg, each), and Tween® 80 (2%, w/v) was prepared through the emulsification-solvent-evaporation technique, which exhibited a 452.4 ± 33.19 nm spheroidal-sized particulate material with narrow particle size distributions, −38.5 ± 1.4 mV zeta potential, and an entrapment efficiency of 79.8 ± 1.9%. The GSH formulation was orally delivered, and biologically tested to ameliorate the CP-induced renal toxicity in a rat model. Detailed renal morphology, before and after the GSH-NLCs administration, including the histopathological examinations, confirmed the ameliorating effects of the prepared glutathione formulation together with its safe oral delivery. CP-induced oxidative stress, superoxide dismutase depletion, elevation of malondialdehyde levels, depletion of Bcl-2 concentration levels, and upregulated NF-KB levels were observed and were controlled within the recommended and near normal/control levels. Additionally, the inflammatory mediator marker, IL-1β, serum levels were marginally normalized by delivery of the GHS-NLCs formulation. Oral administration of the pure glutathione did not exhibit any ameliorating effects on the renal tissues, which suggested that the pure glutathione is reactive and is chemically transformed during the oral delivery, which affected its pharmacological action at the renal site. The protective effects of the GSH-NLCs formulation through its antioxidant and anti-inflammatory effects suggested its prominent role in containing CP-induced renal toxicity and renal tissue damage, together with the possibility of administrating higher doses of the anticancer drug, cyclophosphamide, to achieve higher and effective anticancer action in combination with the GSH-NLCs formulation.

In vivo Evaluation of Nanostructured Lipid Carrier System in Rats Bearing Breast Tumor

The aim of this work is to study the anti-proliferative potential of two anticancer drugs loaded in nanostructured lipid carriers (NLCs).The maximal inhibition of cell growth by Raloxifene (RLX) & Curcumin (CUM) nanostructured lipid carriers (RLX-CUM-NLCs) was determined by assessing the viability of MDA-MB 231 cells. As far as we know, this is the first research to look at the effects of RLX-CUM-NLCs on DMBA-induced breast carcinogenesis in a rat model. RLX-CUM-NLCs reduced the number of tumors in an in-vivo investigation. After 14 weeks of induction, we discovered a tumor with a 100% incidence rate. The incidence of experimental breast cancer was decreased to 83.33% in the RLX-treated group. In contrast, RLX-CUM-NLCs demonstrated a significant anticancer effect with a 50% incidence in the RLX-CUM-NLCs group. Compared to controls, the RLX-CUM-NLCs therapy did not cause any toxicity in the animals in terms of food intake, body weight, or activity levels until 300 mg/kg BW. The current research shows that the RLX-CUM-NLCs has a chemopreventive impact on DMBA-induced breast cancer in rats by decreasing tumor burden and restoring marker enzymes activity.

Comparison of the Release rate, Penetration and Physical stability of p-Methoxycinamic acid (PMCA) in Nanostructured Lipid Carriers (NLC), Solid Lipid Nanoparticle (SLN) and Nanoemulsion (NE) systems

Objective: The p-methoxycinnamic acid (PMCA) was known has antiinflamatory effect which is difficult to dissolve in water, to increase the penetration to the skin it’s was loaded in the nanostructured lipid carrier (NLC) delivery system used the combination of beeswax-cacao oleum and virgin coconut oil (VCO), compared with solid lipid nanoparticle (SLN) and nanoemulsion (NE) delivery systems. Material and Method: PMCA concentrations of 1% in each system were prepared by the high shear homogenization method, namely NLC-PMCA and SLN-PMCA; and was prepared by emulsification method namely NE-PMCA. Then all systems are characterized and tested for release rate, penetration into the rat skin, also were tested for physical stability. The results of this research: All systems have a pH value in the range of 4.2 - 4.5 which falls into the skin's pH range (4-6.5). The viscosity of the NLC-PMCA, SLN-PMCA and NE-PMCA systems are 30.03±6.29; 93.77± 6.11 and 3.43±0.16 cPs, respectively. The particle size of NLC-PMCA, SLN-PMCA and NE-PMCA are 423.6± 33.6; 830.7±71.3 and 57.1±1.6nm, respectively. The release rate of PMCA in the NLC-PMCA, SLN-PMCA and NE-PMCA system are 0.2210±0.0089; 0.1972±0.0145 and 0.4690±0.0228µg/cm2/minute, respectively. The depth of PMCA penetration in the NLC-PMCA, SLN-PMCA and NE-PMCA system at 30 minutes after application are 1173.0±37.8; 703.3±117.2; 1414.3±106.4µm, respectively and at 2 hours after application are 1268.8±111.9; 945.6±140.4; 1832.5±92.8μm, respectively. The NLC-PMCA has no physical changes in 14 days’ storage, whereas the SLN-PMCA consistency becomes thicker and the NE-PMCA becomes turbid. Conclusion: NLC-PMCA has better release rate and deeper penetration than SLN-PMCA, even though it is lower and shallower than NE-PMCA, but NLC-PMCA has better physical stability than SLN-PMCA and NE-PMCA.