Folate and cell penetrating peptide modification effects on penetration behavior of nanostructured lipid carriers using multicellular tumor spheroids

Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect penetration abilities of nanostructured lipid carriers（NLC）. Real--time penetration of folate--or cell penetrating peptide（CPP）-modified NLC was evaluated using a multicellular tumor spheroid（MTS） established by stacking culture method as an in vitro testing platform. The results suggested that CPP modification had a better penetration behavior both on penetration depth and intensity compared with folate-modified NLC at the early stage of penetration process.

Preparation of the nanostructured lipid carriers of artemisinin and its pharmacokinetic evaluation

Artemisinin（ART） is a widely used active drug for malaria, including severe and cerebral malaria. However, its therapeutic efficacy is affected by its lower bioavailability. In the present study, nanostructured lipid carriers（NLCs） were proposed as carrier of ART to improve pharmacokinetic properties of the drug. ART-NLC was prepared by high-pressure homogenization based on orthogonal design. The particle size, zeta potential, encapsulation efficiency（EE） and percentage of drug loading（DL） of ART-NLC were（53.06±2.11） nm,（–28.7±3.59） m V, 73.9%±0.5% and 11.23%±0.37%, respectively. ART-NLC showed the sustained release characteristics and scarcely the hemolysis effect on human red blood cells. The pharmacokinetics of ART-NLC for rats after tail intravenous injection（i.v） or intraperitoneal injection（i.p） were investigated by liquid chromatography-tandem mass spectroscopy（LC-MS/MS）. And ART solution was designed as control preparation. For rats of i.v groups, the AUC0–∞（（707.45±145.65） ng·h/m L） of ART-NLC were significantly bigger than that of ART（（368.98±139.58） ng·h/m L）. The MRT（（3.38±0.46） h） of ART-NLC was longer than that of ART（（1.39±0.61） h）. And similar results were observed for rats of i.p groups. The AUC0–∞（（1233.06±235.57） ng·h/m L） and MRT（（4.97±0.69） h） of ART-NLC were both bigger than those of ART, which were（871.17±234.03） ng·h/m L） and（1.75±0.31） h）, respectively. Compared with ART, ART-NLC showed a significant increase in AUC0–∞（P〈0.05） and MRT（P〈0.001） for both i.p and tail i.v administrations.

Intranasal delivery of nanostructured lipid carriers,solid lipid nanoparticles and nanoemulsions:A current overview of in vivo studies

The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results.In addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc delivery.This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain delivery.Based on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration.The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out.Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the brain.These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.

Sustained-release genistein from nanostructured lipid carrier suppresses human lens epithelial cell growth

AIM： To design and investigate the efficacy of a modified nanostructured lipid carrier loaded with genistein（Gen-NLC） to inhibit human lens epithelial cells（HLECs） proliferation.·METHODS： Gen-NLC was made by melt emulsification method. The morphology, particle size（PS）, zeta potentials（ZP）, encapsulation efficiency（EE） and in vitro release were characterized. The inhibition effect of nanostructured lipid carrier（NLC）, genistein（Gen） and Gen-NLC on HLECs proliferation was evaluated by cell counting kit-8（CCK-8） assay, gene and protein expression of the proliferation marker Ki67 were evaluated with real-time quantitative polymerase chain reaction（RT-q PCR） and immunofluorescence analyses.·RESULTS： The mean PS of Gen-NLC was 80.12±1.55 nm with a mean polydispersity index of 0.11±0.02. The mean ZP was-7.14 ±0.38 m V and the EE of Gen in the nanoparticles was 92.3% ±0.73%. Transmission electron microscopy showed that Gen-NLC displayed spherical-shaped particles covered by an outer-layer structure. In vitro release experiments demonstrated a prolonged drug release for 72 h. The CCK-8 assay results showed the NLC had no inhibitory effect on HLECs and Gen-NLC displayed a much more prominent inhibitory effect on cellular growth compared to Gen of the same concentration. The m RNA and protein expression of Ki67 in LECs decreased significantly in Gen-NLC group.·CONCLUSION： Sustained drug release by Gen-NLCs may impede HLEC growth.

Capillary electrophoresis to determine entrapment efficiency of a nanostructured lipid carrier loaded with piroxicam

A simple and fast capillary electrophoresis method has been developed to determine the amount of piroxicam loaded in a drug delivery system based on nanostructured lipid carriers（NLCs）.The entrapment efficiency of the nanostructured lipid carrier was estimated by measuring the concentration of drug not entrapped in a suspension of NLC.The influence of different parameters on migration times,peak symmetry,efficiency and resolution was studied;these parameters included the pH of the electrophoretic buffer solution and the applied voltage.The piroxicam peak was obtained with a satisfactory resolution.The separation was carried out using a running buffer composed of 50 mM ammonium acetate and 13.75 mM ammonia at pH 9.The optimal voltage was 20 kV and the cartridge temperature was 20 ℃.The corresponding calibration curve was linear over the range of 2.7-5.4 μg/mL of NLC suspension.The reproducibility of migration time and peak area were investigated,and the obtained RSD%values（n = 5） were 0.99 and 2.13.respectively.

Nanostructured lipid carrier based topical gel of Ganoderma Triterpenoids for frostbite treatment

The objective of this study was to prepare nanostructured lipid carrier(NLC)-based topical gel of Ganoderma Triterpenoids(GTs) and evaluate their effects on frostbite treatment. GT-NLCs was prepared by the high pressure homogenization method and then characterized by morphology and analyses of particle size, zeta potential, entrapment efficiency(EE), and drug loading(DL). The NLCs was suitably gelled for skin permeation studies in vitro and pharmacodynamic evaluation in vivo, compared with the GT emulgel. The GT-NLC remained within the colloidal range and was uniformly dispersed after suitably gelled by carbopol preparation. Transmission electron microscopy(TEM) study showed GT-NLCs was spherical in shape. The EE(%) and DL(%) could reach up to(81.84 ± 0.60)% and(2.13 ± 0.12)%, respectively. The result of X-ray diffractograms(XRD) showed that GTs were in an amorphous state in the NLC-gel. In vitro permeation studies through rat skin indicated that the amount of GTs permeated through skin of GT-NLCs after 24 h was higher than that of GT emulsion, and GT-NLCs increased the accumulative amounts of GTs in epidermis 7.76 times greater than GT emulsion. GT-NLC-gel was found to possess superior therapeutic effect for frostbite, compared with the GT emulgel. The NLC based topical gel of GTs could improve-their therapeutic effect for frostbite.

Antitumor activity and biodistribution of DHA-NLC formulation in sarcoma 180-bearing mice

Lipid nanoparticles have become attractive for its prominent properties recent years. In this paper, in vivo anti-tumor efficacy of nanostructured lipid carrier of dihydroartemisinin （DHA-NLC） were evaluated in sarcoma 180-bearing mice model through intraperitoneal （i.p.） administration. In vivo biodistribution was also investigated in Kunming mice bearing S180. Results demonstrated that the intraperitoneally injected DHA-NLC could significantly inhibit tumor growth at the dose levels of 20, 40 and 80 mg/kg, and their inhibition rates were 71.24%, 79.20% and 85.74%, respectively. The biodistribution of DHA after intraperitoneal injection of DHA-NLC in S180-bearing mice is remarkably different from the DHA solution. Therefore, DHA encapsulated in NLC does demonstrate superior anticancer effect to DHA suspension on S 180-bearing mice at the same dose and displayed a dose-dependent antitumor efficacy.