Journal of Liposome Research最新文献

Chemotherapy remains a cornerstone of cancer treatment, yet its lack of tumor specificity often leads to systemic toxicity and limits the maximum tolerable dose. To address these limitations, drug-loaded nanocarriers responsive to ionizing radiation have emerged as a promising strategy to achieve localized drug release within irradiated tumor regions, thereby enhancing therapeutic efficacy while minimizing off-target effects. However, current radiation-responsive nanosystems often exhibit limited drug release at clinically relevant radiation doses. In our previous work, we evaluated liposomal formulations varying lipid composition, sensitizers, and particle size. While these systems demonstrated moderate immediate release upon irradiation followed by sustained passive leakage, they were incompatible with remote drug loading and failed to achieve rapid release. In the present study, we optimized the liposomal membrane composition through modulation of polyunsaturated and saturated phospholipids to enhance radiation sensitivity and colloidal stability. Furthermore, we introduced a radiosensitization mechanism based on the encapsulation of Fe³⁺ ions, which are reduced to Fe²⁺ upon γ-irradiation. This redox transition triggers a Fenton-like reaction that catalyzes the degradation of lipid hydroperoxides, leading to localized lipid peroxidation and membrane disruption. This dual strategy, membrane composition tuning and iron-mediated oxidative activation, resulted in significantly enhanced drug release upon exposure to low-dose radiation.

Despite advances in retinal therapeutics, drug delivery remains hindered by ocular barriers and rapid clearance. Liposomes provide a promising strategy due to their capacity to enhance drug retention, protect labile compounds, and enable targeted delivery to the retina. Conventional eye drop formulations are inadequate for sustained retinal delivery, highlighting the need for optimized nanocarriers. Our systematic review examined how variations in liposomal composition influence drug delivery efficiency in posterior segment eye diseases. In vivo and ex vivo studies published until November 11, 2025 were systematically searched in PubMed-MEDLINE and SCOPUS. Fourteen studies were included, focusing on liposome preparation methods, particle size, and ocular targeting. Risk of bias (ROB) was assessed using the SYRCLE tool, and the review adhered to PRISMA 2020 guidelines (protocol registered in PROSPERO: CRD42024513400). Findings indicated that lipid-to-cholesterol ratios, surface modifications, and polymer coatings substantially affected particle size, encapsulation efficiency, and drug bioavailability at the retina. While these modifications improved therapeutic outcomes, challenges persist in achieving sustained release and clinical reproducibility. ROB assessment revealed methodological limitations across studies. Due to heterogeneity, we performed semi-quantitative weight-of-evidence data correlation to compare the studies. Standardizing formulation strategies and preparation protocols is essential. Future research should prioritize optimized lipid compositions and noninvasive delivery methods to enhance retinal penetration and retention.

The present study aimed to fabricate PEGylated flexosomes (PFs) for intranasal delivery of quetiapine (QTP), addressing its poor oral bioavailability. QTP-loaded PFs were formulated via thin-film hydration and optimized using a 2³ factorial design to evaluate Brij type and concentration, with or without 0.1% cholesterol, providing ultradeformable nanovesicles capable of efficient brain targeting. Brij surfactants served dual roles as elasticity-enhancing edge activators and PEGylating agents, thereby improving steric stabilization and mucosal interactions. The formulae were assessed by determining particle size, entrapment efficiency, polydispersity, zeta potential, and drug release. The optimized formulation (QTP-OPF) was assessed for deformability, stability, morphology, and ex vivo nasal permeation. Finally, in vivo pharmacokinetic and histopathological assessments were accomplished to estimate the in vivo performance of QTP-OPF. The QTP-OPF exhibited reduced particle size and polydispersity, a high zeta potential, and enhanced drug release. Additionally, it demonstrated superior deformability and maintained stability for 90 days. Transmission electron microscopy confirmed spherical, PEG-coated vesicles. The ex vivo nasal permeation study revealed a 1.6-fold increase over QTP suspension, while in vivo pharmacokinetics revealed a 3.8-fold enhancement in brain C_max and a 7.5-fold higher brain AUC_0-∞. Histopathological evaluation confirmed the formulation's safety. PFs present a promising platform for enhanced intranasal QTP delivery.

Archaeal lipids offer a useful strategy for improving liposomal systems because of their inherent stability under extreme conditions. Incorporating lipids from Aeropyrum pernix K1 allowed us to optimize sphingomyelin-cholesterol formulation. These archaeal lipids enabled complete recovery of liposome morphology after destabilization with 4 mM Ca²⁺ followed by EDTA, indicating that membrane integrity is maintained in the presence of calcium. This is noteworthy given the anionic nature of the archaeal lipids, which in this case provide colloidal stability without increasing sensitivity to Ca²⁺. The addition of 2 mol% archaeal lipids also supported high encapsulation efficiency of 95% for active vincristine loading and performed better than the binary mixture when vesicles were prepared by extrusion without cosolvents. Furthermore, reducing the archaeal lipid fraction preserved biological stability provided by sphingomyelin-cholesterol, as confirmed by flow cytometry and fluorescence microscopy, whereas pure archaeosomes composed entirely of archaeal lipids have been reported to show poor stability in biological systems.

Tomatoes are susceptible to a variety of pathogens, including bacteria, which can significantly impact plant yield and quality. The application of natural antibacterial agents, such as juglone, has shown promise in the biocontrol of these pathogens. The main objective of this study was to investigate the effects of liposomal encapsulation on enhancing the bioavailability of juglone as a biocontrol agent. The entrapment of juglone in nanoliposomes as water-soluble cyclodextrin complexes represents a novel strategy that merges the distinct advantages of these two systems into one. In this study, the juglone/β-cyclodextrin inclusion complex was successfully encapsulated in nanoliposomes (J/β-CD/L). Physicochemical and morphological characterizations of the formulations were conducted. The release of juglone from liposomes exhibited a cumulative release of 46.73% at 72 hours. The MIC values of the J/β-CD/L molecule against plant pathogenic bacteria Pseudomonas syringae pv. tomato strain SH-1 (Pst), Xanthomonas euvesicatoria strain SH-2 (Xeu), and Clavibacter michiganensis subsp. michiganensis strain SH-3 (Cmm) were 68.93 µg/mL, 34.47 µg/mL, and 68.93 µg/mL, respectively. These MIC values were found to be lower than free juglone. Based on the seed germination results, the prepared formulation did not show any phytotoxic effect on tomato seeds at the applied concentrations. Thus, the nanoliposomal encapsulation technique appears to be a promising method for enhancing the antibacterial effectiveness of juglone as a biocontrol agent.

This study investigated the use of ultradeformable bilosomes (UBs)-loaded buccal films to overcome the limited oral bioavailability of olmesartan medoxomil (OLM), a poorly water-soluble antihypertensive. UBs were prepared via thin film hydration technique, and a 2⁴ factorial design evaluated the effects of phosphatidylcholine to bile salt (PC: BS) ratio, permeation enhancer (PE) type and amount, and sonication time on entrapment efficiency (EE), particle size (PS), zeta potential (ZP), and polydispersity index (PDI). The optimized formulation (UBs-12), comprising 50 mg Labrasol^® at an 8:1 PC: BS ratio and sonicated for 4 minutes, showed EE% of 67.9 ± 1.9%, PS of 279.8 ± 3.5 nm, ZP of -46.9 ± 1.4 mV, and PDI of 0.46 ± 0.02. It showed a markedly higher OLM release after 24 h (78.5 ± 2.4%) compared to conventional bilosomes and aqueous OLM suspension, as well as a significantly greater deformability index (18.2 ± 0.3) (p = 0.008) than conventional bilosomes. UBs-12 was incorporated into buccal films with favorable in vitro characteristics. Pharmacodynamic assessment in dexamethasone-induced hypertensive male rats demonstrated that UBs-12 films achieved a more pronounced and sustained blood pressure reduction compared to oral suspension. The films yielded a 1.68-fold increase in area under the antihypertensive effect-time curve and a 1.75-fold longer effect half-life. These results support UBs-loaded buccal films as a promising approach to enhance OLM bioavailability.

Bilosomes have been investigated as potential carrier for ocular delivery. Ocular viral infection may lead to direct or autoimmune damages, uveoretinitis, and disturbed vision. In this work, we fabricated ganciclovir (antiviral agent) and resveratrol (natural antioxidant and anti-inflammatory) coloaded bilosomes. The influence of bile salt concentration and chitosan coating was investigated. Formulations were subjected to physicochemical characterizations and the selected formulations were assessed for structural analyses, in vitro release, ex vivo corneal permeation, and in vivo appraisal. Increasing bile salt concentration resulted in an increase in particle diameter and zeta-potential negativity, while chitosan coating increased vesicular size and shifted the zeta potential to positive values. F3 (containing 10 mg/mL sodium taurocholate) and F4 (chitosan coated F3) showed satisfying results of physicochemical characteristics. Structural analyses proved that lipophilic resveratrol was located in lipid bilayer while hydrophilic ganciclovir was located in aqueous core of the vesicles and both of them were in an amorphous state. F4 provided excellent ocular delivery of resveratrol and ganciclovir presented by higher transcorneal flux (3.27 ± 0.28 and 2.31 ± 0.17 μg/cm²/h, respectively) and permeability coefficient (1.64 ± 0.09 and 1.15 ± 0.08 cm²/h, respectively) when compared to F3 and drugs' suspension. Histological evaluation demonstrated that F4 surpassed F3, showing non-irritant properties and marked anti-inflammatory activity. Conclusively, these findings suggested that F4 coloaded with ganciclovir and resveratrol might be a promising strategy for the feasible treatment of ocular viral infection and its accompanying inflammatory symptoms.

Bone-related diseases and bone cancers remain challenging to treat due to limited targeted therapies and significant off-target side effects. This study presents the development of a bone-targeted liposomal formulation, termed Bone Binding Liposomes (BBL), functionalized with a pyrophosphate-cholesterol derivative to enhance binding to bone mineral (hydroxyapatite). Our experiments demonstrated the superior affinity of BBL compared to conventional Non-Binding Liposomes (NBL). Moreover, both formulations efficiently encapsulated a prototype drug and both exhibited comparable biocompatibility, both preserving the drug's physicochemical properties on elective target cells, macrophages. This targeted delivery system holds a potential for treating bone-related diseases, offering a means to improve targeted delivery and reduce off-target effects.

Liposomes are used as a vehicle in targeted drug delivery due to inherent biocompatibility and encapsulative potential for diverse bioactive agents. However, consistent production remains challenging. With the help of microfluidic systems, liposome synthesis can be precisely controlled, conferring consistency and scalability. This review focuses on the integration of innovative microfluidic-based liposome synthesis and artificial intelligence (AI), specifically machine learning (ML), for the design of optimal critical quality attributes (CQAs), such as vesicle size, size distribution and encapsulation efficiency. ML models such as artificial neural networks (ANN), support vector machines (SVM), and random forest (RF) can predict liposome quality with limited input data. Together with design-of-experiment (DoE), these paradigms provide data-driven optimization. However, the interpretability of the model is enhanced by explainable AI (XAI) tools such as SHAP, which identify determinants for every prediction. The integration of these methods makes an advance toward robust and scalable liposome design. We have also summarized the challenges and future perspectives of scaling AI-guided microfluidic platforms into mainstream pharmaceutical development.

The enzymatic degradation of bile acid-modified phospholipids by secretory phospholipase A₂ (sPLA₂) can induce membrane disruption in liposomes. However, the influence of bile acid hydrophilicity on this disruptive effect remains unclear. In this study, we synthesized four lipids by conjugating lithocholic acid (LCA: 3α-OH), chenodeoxycholic acid (CDCA: 3α-OH, 7α-OH) or its derivatives (7k-CDCA: 3α-OH, 7 = O; bk-CDCA: 3 = O, 7 = O) to a phosphocholine backbone. We found that sPLA₂-mediated release of 6-carboxyfluorescein (6-CF) from liposomes was significantly faster with LCA-PC (100% release) than with the more hydrophilic CDCA-, 7k-CDCA-, or bk-CDCA-PC (14-30% release) in 2 hours. Assays of enzymatic degradation rates indicated that the low efficacy of CDCA-PC and 7k-CDCA-PC correlated with their slow hydrolysis by sPLA₂. Although bk-CDCA-PC was degraded at a rate (13.01%) similar to LCA-PC (15.07%) in 2 hours, dialysis experiments revealed that its metabolite (bk-CDCA) readily diffused into the aqueous phase, unlike LCA, which remained anchored to the membrane. This demonstrates that the firm interfacial settlement of the bile acid metabolite is crucial for the membrane-disruptive effect. Our findings establish that increased hydrophilicity of the bile acid moiety attenuates the sPLA₂-induced pore-forming effect, providing a critical guideline for the future design of sPLA₂-responsive liposomal systems.