The main reasons for the difficulty in curing and high recurrence rate of glioblastoma multiforme (GBM) include: 1. The difficulty of chemotherapy drugs in penetrating the blood-brain barrier (BBB) to target tumor cells; 2. The presence of glioma stem cells (GSCs) leading to chemotherapy resistance. Therefore, breaking through the limitations of the BBB and overcoming the drug resistance caused by GSCs are the main strategies to address this problem. This study presents our results on the development of lactoferrin/CD133 antibody conjugated nanostructured lipid carriers (Lf/CD133-NLCS) for simultaneously targeting BBB and GSCs. Temozolomide (TMZ) loaded Lf/CD133-NLCS (Lf/CD133-NLCS-TMZ) exhibited high-efficiency in vitro anti-tumor effects toward malignant glioma cells (U87-MG) and GSCs, while demonstrating no significant toxicity to human normal macrophages and L929 cells at concentrations lower than 200 μg/mL. The results of the in vitro targeting GBM study revealed a notably higher cellular uptake of Lf/CD133-NLCS-TMZ in U87-MG cells and GSCs in comparison to NLCS-TMZ. This suggests that the active targeting of GBM was enhanced following Lf/CD133 modification. In addition, increased BBB permeability were confirmed for Lf/CD133-NLCS-TMZ compared to NLCS-TMZ both in vitro and in vivo. Taking the results together, Lf/CD133-NLCS-TMZ show great potential for dual targeting of BBB and GSCs, as well as GBM therapy based on this strategy. .

UNASSIGNED: Oral drug administration is the most common and convenient route, offering good patient compliance but drug solubility limits oral applications. Celecoxib, an insoluble drug, requires continuous high-dose oral administration, which may increase cardiovascular risk. The nanostructured lipid carriers prepared from drugs and lipid excipients can effectively improve drug bioavailability, reduce drug dosage, and lower the risk of adverse reactions.
UNASSIGNED: In this study, we prepared hyaluronic acid-modified celecoxib nanostructured lipid carriers (HA-NLCs) to improve the bioavailability of celecoxib and reduce or prevent adverse drug reactions. Meanwhile, we successfully constructed a set of FDA-compliant biological sample test methods to investigate the pharmacokinetics of HA-NLCs in rats.
UNASSIGNED: The pharmacokinetic analysis confirmed that HA-NLCs significantly enhanced drug absorption, resulting in an AUC0-t 1.54 times higher than the reference formulation (Celebrex®). Moreover, compared with unmodified nanostructured lipid carriers (CXB-NLCs), HA-NLCs enhance the retention time and improve the drug\'s half-life in vivo.
UNASSIGNED: HA-NLCs significantly increased the bioavailability of celecoxib. The addition of hyaluronic acid prolonged the drug\'s in vivo duration of action and reduced the risk of cardiovascular adverse effects associated with the frequent administration of oral celecoxib.

Chronic obstructive pulmonary disease (COPD) is a prevalent lung condition characterized by airflow obstruction, disability, and high mortality rates. Magnolol (MA), known for its anti-inflammatory and antioxidant properties, holds the potential for alleviating COPD symptoms. However, MA faces challenges like poor aqueous solubility and low bioavailability. Herein MA-loaded nanostructured lipid carriers (MA-NLC) were prepared using emulsification and solvent evaporation. These carriers exhibited a particle size of (19.67 ± 0.36) nm, a polydispersity index of (0.21 ± 0.01), and a zeta potential of (-5.18 ± 0.69) mV. The fine particle fraction of MA-NLC was (68.90 ± 0.07)%, indicating minimal lung irritation and enhanced safety. Pulmonary delivery of MA-NLC via nebulizer actively targeted the diseased lung tissues, facilitated slow release, and overcame the challenges of low oral absorption and bioavailability associated with MA. This formulation prolonged the residence time of MA and optimized its therapeutic effect in pulmonary tissues. Upon pulmonary administration, MA-NLC effectively regulated inflammatory and oxidative stress markers in COPD models, demonstrating its potential as a promising therapeutic platform for COPD management.

Mifepristone, a progesterone receptor antagonist, was initially used to terminate early pregnancy. As scientific research advanced, it emerged to be effective in the treatment of various tumors and tumor-like conditions such as endometriosis. Despite the therapeutic potential of mifepristone, its therapeutic effect is still far from ideal because the drug is difficult to dissolve and to accumulate in the target tissue sites. To address this issue, mifepristone-loaded nanostructured lipid carriers (Mif-NLC) were prepared by a simple solvent diffusion method and their anti-endometriosis performance and mechanisms were initially investigated. By optimizing the preparation protocol, we obtained uniform and spheroidal Mif-NLC with an average particle size of 280 nm. The encapsulation rate and drug loading capacity were 64.67% ± 0.15% and 2.7% ± 0.014%, respectively, as measured by UV spectrophotometry. The in vitro release kinetics indicated that mifepristone was released from NLC in a sustained-release manner. Compared with free mifepristone, Mif-NLC exhibited enhanced cellular uptake and inhibition of invasion activity in primary mesenchymal cells of endometriosis. A certain reduction in the size of endometriotic cysts was observed in animals compared to controls. The induction of autophagy via Mif-NLC may serve as the molecular mechanism underlying this effect. Furthermore, observation of uterine structures showed negligible toxic effects. This suggested that mifepristone encapsulated in NLC can improve its bioavailability and anti-endometriosis efficacy, which provided a new strategy for the treatment of endometriosis.

Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8+NKG2D+T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.

Porcine epidemic diarrhea virus (PEDV) is an acute enteric coronavirus, inducing watery diarrhea and high mortality in piglets, leading to huge economic losses in global pig industry. Ivermectin (IVM), an FDA-approved antiparasitic agent, is characterized by high efficacy and wide applicability. However, the poor bioavailability limits its application. Since the virus is parasitized inside the host cells, increasing the intracellular drug uptake can improve antiviral efficacy. Hence, we aimed to develop nanostructured lipid carriers (NLCs) to enhance the antiviral efficacy of IVM. The findings first revealed the capacity of IVM to inhibit the infectivity of PEDV by reducing viral replication with a certain direct inactivation effect. The as-prepared IVM-NLCs possessed hydrodynamic diameter of 153.5 nm with a zeta potential of -31.5 mV and high encapsulation efficiency (95.72%) and drug loading (11.17%). IVM interacted with lipids and was enveloped in lipid carriers with an amorphous state. Furthermore, its encapsulation in NLCs could enhance drug internalization. Meanwhile, IVM-NLCs inhibited PEDV proliferation by up to three orders of magnitude in terms of viral RNA copies, impeding the accumulation of reactive oxygen species and mitigating the mitochondrial dysfunction caused by PEDV infection. Moreover, IVM-NLCs markedly decreased the apoptosis rate of PEDV-induced Vero cells. Hence, IVM-NLCs showed superior inhibitory effect against PEDV compared to free IVM. Together, these results implied that NLCs is an efficient delivery system for IVM to improve its antiviral efficacy against PEDV via enhanced intracellular uptake.

Morellic acid (MA), a typical compound found in Garcinia plants, is known for its anticancer properties. In present study, we isolated MA from resin of Garcinia hanburyi Hook. f. using preparative chromatography. We have successfully prepared MA-loaded nanostructured lipid carriers (MA-NLCs) and refined the production process via orthogonal testing. Optimization of the preparation process resulted in an average particle size of 165.50±1.70 nm with a PDI of 0.19±0.01. The EE% and DL% of MA-NLCs were 78.17±0.34% and 7.25±0.38%, respectively. The zeta potential of MA-NLCs was -21.85±0.67 mV. Comparatively, MA-NLCs showed a greater area under the curve (AUC) and an extended half-life (t1/2) than free MA. Pharmacokinetics analysis revealed that the AUC0-t increased from 4.91±0.65 μg/mL∙min (free MA) to 18.91±3.40 μg/mL∙min (MA-NLCs) and the t1/2 value for MA-NLCs was 7.93-fold longer than that of free MA. In vitro cytotoxic assessments indicated that MA formulations curtailed the proliferation of cancer cells. In vivo, MA-NLCs significantly inhibited the tumor growth in tumor-bearing mouse model. Molecular mechanism studies revealed that up-regulation of apaf-1 and activation of caspase-3, caspase-9 and GSDME by MA-NLCs may trigger to apoptosis and pyroptosis in cancer cells. Consequently, our findings support the potential of NLCs as an effective MA delivery system for the clinical management of cancer.

The objective of the present study was to develop and evaluate NLC-chitosan hydrogel beads for topical administration. The feasibility of the preparation technology was verified by investigating various formulation factors and the impact of chitosan hydrogel beads on the NLC. The encapsulation efficiency of NLC-chitosan hydrogel beads was above 95% in optimized process conditions. The physical characterization of the NLC-chitosan hydrogel beads showed that the NLC was distributed within the network of the chitosan hydrogel beads. Furthermore, the incorporation of NLC into the chitosan hydrogel beads was related to the electrostatic interaction between the surface of the NLC and chitosan, which influenced the lipid ordering degree of the NLC and contributed to the stability. The stability studies showed that the retention rate of quercetin in the NLC-chitosan hydrogel beads was 88.63 ± 2.57% after 10 months of storage under natural daylight. An in vitro permeation study showed that NLC-chitosan hydrogel beads exhibited superior ability in enhancing skin permeation by hydrophobic active ingredients compared to the NLC and significantly increased skin accumulation. These studies demonstrated that the use of NLC-chitosan hydrogel beads might be a promising strategy for the delivery of hydrophobic active ingredients in topical administration.

In this current study, the internal structure of nanostructured lipid carriers was modulated by phospholipids (lecithin PC, hydrogenated soybean phospholipid HPC) and solid lipids to achieve stable encapsulation of citral. The presence of high melting point HPC could construct α-crystalline type with more lattice defects and effectively inhibit β-ization. The HPC group could maintain the particle size at 155.9-186.9 nm, the polydispersity index (PDI) at 0.182-0.321, the Zeta potential at -57.58 mV to -49.35 mV and the retention rate of citral at 91.33-98.49 % in the acidic environments of 2 mM and 20 mM hydrochloric acid solutions. The recrystallization index (RI) of NLC increased with the number of solid lipid ester bonds (from 3.57 % to 16.58 % in the PC group and from 0.82 % to 12.47 % in the HPC group). The results illustrated that the number of solid lipid ester bonds and the melting point of phospholipids affected crystallinity of the lipid matrix and thus the stability of encapsulated citral. Hydrogenated phospholipid with high melting points was more beneficial in stabilizing citral. The present study improved the acidic stability of citral and provided a new thought for the application of citral in acidic beverages.

Surface modification of nanostructured lipid carriers (NLCs) can be an effective way to improve their oral delivery for active ingredients. In this study, four type of guar gum series modified NLCs for the delivery of phytosterols (PS) were constructed and the effects of the polysaccharides on their structure and physicochemical properties were studied. DLS and AFM results revealed that positively charged polysaccharides could bind to PS-NLCs through electrostatic attraction and made the complexes finally take positive charges, while negatively charged polysaccharides were more likely to fill in the gaps of NLC systems to achieve a balance between electrostatic repulsion and intermolecular forces. Although all four polysaccharides exhibited good storage stability and controlled release of PS in simulated intestinal digestion, PS-NLCs modified with partially hydrolyzed cationic guar gum (PHCG) at medium or high concentrations exhibited better gastric stability, mucoadhesion, and cellular uptake, which had considerable significance for improving the oral bioavailability of PS. This might be related to the coating structure of PHCG-PS-NLCs confirmed by AFM, FTIR, and Raman characterization. This study provide a reference value for designing suitable PS-NLC complexes without synthetic surfactants.