Preparation and characterization of a nanostructured lipid carrier for phenylethyl resorcinol

Phenylethyl resorcinol(PR)demonstrates inhibitory effects on multiple targets in the melanin synthesis pathway,resulting in a strong whitening effect.However,challenges such as limited solubility in water and susceptibility to oxidation and discoloration restrict its practical application in the cosmetics industry.In order to enhance stability and performance characteristics,a whitening nanostructured lipid carrier(NLC)was synthesized through high-pressure homogenization.This method entailed the incorporation of solid lipids,a liquid lipid,and a compound emulsifier,with deionized water fulfilling the roles of solid phase,liquid phase,and water phase,respectively.The NLC's particle size,Zeta potential,stability,encapsulation efficiency,and other parameters were assessed using techniques such as particle sizer,stability analyzer,and HPLC.The results showed that the NLC for phenylethyl resorcinol prepared by using the optimal formula(7.50%solid lipids,3.00%ethylhexyl palmitate,and 2.00%Tween 80 and soybean lecithin)has an encapsulation efficiency of 87.11%,a particle size of 157.2±0.70 nm,a kinetic instability of less than 1.2,and a greatly improved stability,thereby successfully solving the problems of unstable storage and poor solubility of phenylethyl resorcinol.

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 for bioactive rice bran gamma-oryzanol

The current work presents the development of a nanostructured lipid carrier(NLC)as a colloidal encapsulation and controlled release system for bioactiveγ-oryzanol(GO)from rice bran oil.GO-loaded NLC(GO-NLC)were prepared using rice bran oil GO via a hot homogenisation method with sunflower oil(liquid lipid)and stearic acid(solid lipid)as the encapsulating lipid matrix,and rice bran phospholipids and Tween 80 as stabilisers.Fabricated GO-NLC had a 95%encapsulation efficiency with a spherical‘yolk–shell’morphology and a 143 nm mean particle diameter.A 60-day storage stability study showed that GO-NLC had high GO retention(>90%)at ambient temperature in light and dark conditions.In vitro release studies demonstrated that GO can be released from GO-NLC via different modes:slow controlled release into simulated intestinal fluid,following the Korsmeyer-Peppas model,and rapidly into a surfactant solution(Tween 80),following first-order release kinetics.Lastly,in vitro studies showed encapsulation of GO in NLCs afforded an 18-fold increase in free radical-scavenging activity,a two-fold increase in hyaluronidase-inhibitory,and a 200-fold improvement in anti-inflammatory activity.These suggest that GO-NLC is a suitable GO delivery system,which can either perform as an oral extended-release formulation or a rapid-release,surfactant triggered system,with improved health-promoting bioactivities.

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.

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.

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.

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.

A notable impact of lipid matrices on cholesterol bioaccessibility from phytosterols-loaded nanostructured lipid carriers during in vitro intestinal digestion

Encapsulation of phytosterols in nanostructured lipid carriers(NLCs)is an effective approach to improve their physicochemical properties,but the interaction of phytosterols in NLCs with cholesterol can be affected by lipid matrices.The objective of this study was to screen a desired phytosterols-loaded NLC(PS-NLC)formulation to reduce the absorption of intestinal cholesterol.A series of formulations were prepared using amphipathic glycerol monostearate(GMS)as the solid lipid fraction to increase lipid compatibity with phytosterols.All formulations showed a lowering effect on cholesterol bioaccessibility through in vitro intestinal digestion.And the PS-NLCs with medium chain triglycerides(MCT)as the liquid lipid showed significantly higher inhibition of cholesterol bioaccessibility(accessible fraction for intestinal absorption)than the formulations with long chain triglycerides(LCT),which could due to the solubilization of cholesterol by hydrolysis products of LCT,suggesting a notable impact of lipid type on cholesterol bioaccessibility.Furthermore,the analysis of distribution of phytosterols and cholesterol revealed a cocrystallization mechanism occurred during in vitro digestion.This study provides a certain reference for designing phytosterol-ingredient agents with a better hypocholesterolemic effect in water-dispersible functional foods.

Sargassum horneri extracts loaded nanostructured lipid carriers:Preparation,physicochemical properties,and in vitro antioxidant activity studies

This study tried to establish optimal conditions for Sargassum horneri extracts loaded nanostructured lipid carriers(SHE-NLCs).Therefore,we observed various physicochemical analyzes,sugar and phenolic contents,and anti-oxidants while storing the SHE-NLCs for 28 days at different SHE addition amounts(0%-0.5%)and storage temperatures(25 and 65℃).All SHE-NLCs stored at 25℃ showed a small hydrodynamic diameter(20.1-25.4 nm)and high encapsulation efficiency(64.1%-89.3%)for 28 days.As the amount of SHE increased,the pH and electrical conductivity of SHE-NLCs significantly decreased and increased,respectively(p<0.05).Also,at 25℃,prevented a sharp decrease in the total phenolic content and antioxidant activity of SHE-NLCs as the storage period increased compared to 65℃.SHE 0.25%loaded NLCs can stably maintain the formulation structure for 28 days at room temperature while being an amount sufficiently containing the functionality of SHE.

Nanostructured lipid carrier as a strategy for encapsulation of formononetin and perilla seed oil:In vitro characterization and stability studies

This study aims to characterize formononetin(FMN)and perilla seed oil(PSO)co-loaded nanostructured lipid carriers(NLC).FMN-PSO-NLC was prepared by melt-emulsification ultrasonic method.The average particle size of FMN-PSO-NLC was 117.5±3.7 nm,with PDI of 0.240±0.017 and zeta potential of-36.7±0.7 mV.Dif-ferential scanning calorimetry(DSC),X-ray diffractometry(XRD),and Fourier transform infrared spectroscopy(FTIR)studies revealed that the formation of FMN-PSO-NLC was accompanied by changes in crystallinity and intermolecular interactions.FMN-PSO-NLC dispersions possessed pseudoplastic flow from the rheological studies.FMN-PSO-NLC possessed sustained-release of FMN for 24 h.FMN-PSO-NLC was more easily digested than that of PSO in vitro digestion.The antioxidant activity and stability of FMN-PSO-NLC were significantly improved.This study provides a formulation design for improving the stability,antioxidant activity of FMN and delaying the oxidation of PSO.

Development of ascorbyl palmitate-loaded nanostructured lipid carriers(NLCs)to increase the stability of Camelina oil

In this study,ascorbyl palmitate(AP)incorporated in nanostructured lipid carriers(NLCs-AP)was fabricated using the hot-homogenization method.The amounts of AP,Tween 80,glyceryl stearate,and oleic acid were optimized by Box-Behnken Design(BBD)to obtain a high percentage of encapsulation efficiency and loading efficiency.Then,the optimum NLCs-AP,free-AP with rosemary essential oil(REO),NLCs-AP with REO,and tert-Butylhydroquinone(TBHQ)at a concentration of 75 ppm were added to camelina oil.Then peroxide value(PV),anisidine value(AV),TOTOX value(TV),oxidative stability using Rancimat,total phenol content(TPC),and antioxidant activity in camelina oil samples were evaluated during 90 days of storage at the ambient temper-ature.The optimum NLCs-AP had a particle size of 133.4 nm and a PDI of 0.29.The transmission electron microscopy(TEM)showed a spherical and smooth surface of the optimum NLCs-AP.The results of differential scanning calorimetry(DSC)and Fourier transfer spectroscopy infrared(FTIR)analyses implied that there was no interaction between AP and NLCs.The Korsmeyer-Peppas model was the best model for the evaluation of the release kinetics.The amounts of PV,AV,and TV of camelina oil containing the optimum NLCs-AP were slightly higher than the oil containing TBHQ.The highest oxidative protection,TPC,and antioxidant activity percentage were achieved in camelina oil containing NLCs-AP with REO.Conclusively,the optimum NLCs-AP had excellent potential for encapsulation of AP,and the mixture of REO and NLCs-AP could be applied for giving suitable oxidative stability in camelina oil.

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.