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Machine learning (ML) has emerged as a transformative tool in drug delivery, particularly in the design and optimization of liposomal formulations. This review focuses on the intersection of ML and liposomal technology, highlighting how advanced algorithms are accelerating formulation processes, predicting key parameters, and enabling personalized therapies. ML-driven approaches are restructuring formulation development by optimizing liposome size, stability, and encapsulation efficiency while refining drug release profiles. Additionally, the integration of ML enhances therapeutic outcomes by enabling precision-targeted delivery and minimizing side effects. This review presents current breakthroughs, challenges, and future opportunities in applying ML to liposomal systems, aiming to improve therapeutic efficacy and patient outcomes in various disease treatments. [ABSTRACT FROM AUTHOR]

Skin cancer is a prevalent global health issue, necessitating ongoing research into innovative treatment approaches. This study focuses on assessing the effectiveness of a liposomal formulation to enhance skin cancer treatment and demonstrates its technological viability. A comprehensive literature review establishes the context by examining current skin cancer treatments and the role of liposomal formulations in dermatological therapies. The research objectives are clearly outlined, detailing the liposomal formulation's characteristics and experimental methodologies. Results from the study, including comparisons with existing treatments and statistical analyses, are presented, offering insights into the formulation's potential for advancing skin cancer therapy. The discussion section interprets the findings, addresses limitations, and underscores the transformative impact of liposomal formulations in skin cancer treatment. The conclusion succinctly summarizes key findings, emphasizing the study's significance. Furthermore, the future directions section outlines potential research avenues and improvements to the liposomal formulation. This research contributes to the evolving landscape of skin cancer treatment, highlighting the promising role of liposomal formulations in enhancing therapeutic outcomes. By bridging the gap between scientific innovation and clinical application, this study provides valuable insights into the potential of liposomal formulations to revolutionize skin cancer treatment, ultimately contributing to improved patient outcomes and a more effective approach to combating this widespread and pressing health concern. [ABSTRACT FROM AUTHOR]

Objectives: NS-87/CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin. NS-87/CPX-351 exerts antileukemic action by maintaining a synergistic molar ratio of cytarabine to daunorubicin of 5:1 within the liposome while in circulation. Patients with high-risk acute myeloid leukemia (AML), which includes therapy-related AML and AML with myelodysplasia-related changes (AML-MRC), have poorer outcomes than those with other AML. Methodology: This open-label phase 1/2 (P1/2) study was conducted in 47 Japanese patients aged 60–75 years with newly diagnosed high-risk AML to evaluate the pharmacokinetics, safety, and efficacy of NS-87/CPX-351. Results: In the 6 patients enrolled in the P1 portion, no dose-limiting toxicities (DLTs) were reported, and 100 units/m2 during the induction cycle was found to be acceptable. Cytarabine and daunorubicin had a long half-life in the terminal phase (32.8 and 28.7 h, respectively). In the 35 patients enrolled in the P2 portion, composite complete remission (CRc; defined as complete remission [CR] or CR with incomplete hematologic recovery [CRi]) was achieved in 60.0% (90% CI: 44.7–74.0) of the patients. Adverse events due to NS-87/CPX-351 were well tolerated. Outcomes: NS-87/CPX-351 can be considered as a frontline treatment option for Japanese patients with high-risk AML. [ABSTRACT FROM AUTHOR]

Systemically vaccinated individuals against COVID-19 and influenza may continue to support viral replication and shedding in the upper airways, contributing to the spread of infections. Thus, a vaccine regimen that enhances mucosal immunity in the respiratory mucosa is needed to prevent a pandemic. Intranasal/pulmonary (IN) vaccines can promote mucosal immunity by promoting IgA secretion at the infection site. Here, we demonstrate that an intramuscular (IM) priming-IN boosting regimen with an inactivated influenza A virus adjuvanted with the liposomal dual TLR4/7 adjuvant (Fos47) enhances systemic and local/mucosal immunity. The IN boosting with Fos47 (IN-Fos47) enhanced antigen-specific IgA secretion in the upper and lower respiratory tracts compared to the IM boosting with Fos47 (IM-Fos47). The secreted IgA induced by IN-Fos47 was also cross-reactive to multiple influenza virus strains. Antigen-specific tissue-resident memory T cells in the lung were increased after IN boosting with Fos47, indicating that IN-Fos47 established tissue-resident T cells. Furthermore, IN-Fos47 induced systemic cross-reactive IgG antibody titers comparable to those of IM-Fos47. Neither local nor systemic reactogenicity or adverse effects were observed after IN delivery of Fos47. Collectively, these results indicate that the IM/IN regimen with Fos47 is safe and provides both local and systemic anti-influenza immune responses.

Betulinic acid is a naturally occurring pentacyclic triterpene belonging to the lupane-group that exhibits a wide range of pharmacological activities. BA derivatives are continuously being researched due to their improved anticancer efficacy and bioavailability. The current research was conducted in order to determine the antiproliferative potential of three synthesized BA fatty esters using palmitic, stearic and butyric acids and their liposomal nanoformulations. The cytotoxic potential of BA fatty esters (Pal-BA, St-BA, But-BA) and their respective liposomal formulations (Pal-BA-Lip, St-BA-Lip, But-BA-Lip) has been assessed on HaCaT immortalized human keratinocytes and A375 human melanoma cells. Both the esters and their liposomes acted as cytotoxic agents against melanoma cells in a time- and dose-dependent manner. The butyryl ester But-BA outperformed BA in terms of cytotoxicity (IC50 60.77 μM) while the nanoformulations St-BA-Lip, But-BA-Lip and BA-Lip also displayed IC50 values (60.11, 50.71 and 59.01 μM) lower compared to BA (IC50 65.9 μM). The morphological evaluation revealed that the A375 cells underwent morphological changes consistent with apoptosis following 48 h treatment with the tested compounds, while the HaCaT cells' morphology remained unaltered. Both the esters and their liposomal formulations were able to inhibit the migration of the melanoma cells, suggesting a significant antimetastatic effect. The quantitative real-time PCR revealed that all tested samples were able to significantly increase the expression of the pro-apoptotic Bax and inhibit the anti-apoptotic Bcl-2 proteins. This effect was more potent in the case of liposomal nanoformulations versus non-encapsulated compounds, and overall, But-BA and its formulation exhibited the best results in this regard. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is highly aggressive and has no standard treatment. Although being considered as an alternative to conventional treatments for TNBC, immunotherapy has to deal with many challenges that hinder its efficacy, particularly the poor immunogenic condition of the tumor microenvironment (TME). Herein, we designed a liposomal nanoparticle (LN) platform that delivers simultaneously toll-like receptor 7 (imiquimod, IQ) and toll-like receptor 3 (poly(I:C), IC) agonists to take advantage of the different toll-like receptor (TLR) signaling pathways, which enhances the condition of TME from a "cold" to a "hot" immunogenic state. The optimized IQ/IC-loaded LN (IQ/IC-LN) was effectively internalized by cancer cells, macrophages, and dendritic cells, followed by the release of the delivered drugs and subsequent stimulation of the TLR3 and TLR7 signaling pathways. This stimulation encouraged the secretion of type I interferon (IFN-α, IFN-β) and CXCLl0, a T-cell and antigen-presenting cells (APCs) recruitment chemokine, from both cancer cells and macrophages and polarized macrophages to the M 1 subtype in in vitro studies. Notably, systemic administration of IQ/IC-LN allowed for the high accumulation of drug content in the tumor, followed by the effective uptake by immune cells in the TME. IQ/IC-LN treatment comprehensively enhanced the immunogenic condition in the TME, which robustly inhibited tumor growth in tumor-bearing mice. Furthermore, synergistic antitumor efficacy was obtained when the IQ/IC-LN-induced immunogenic state in TME was combined with anti-PD1 antibody therapy. Thus, our results suggest the potential of combining 2 TLR agonists to reform the TME from a "cold" to a "hot" state, supporting the therapeutic efficacy of immune checkpoint inhibitors. [Display omitted] [ABSTRACT FROM AUTHOR]

Bacterial lipopolysaccharides (LPS) are potent innate immunostimulants targeting the Toll-like receptor 4 (TLR4), an attractive and validated target for immunostimulation in cancer therapy. Although LPS possess anti-tumor activity, toxicity issues prevent their systemic administration at effective doses in humans. We first demonstrated that LPS formulated in liposomes preserved a potent antitumor activity per se upon systemic administration in syngeneic models, and significantly enhance the antitumor activity of the anti-CD20 antibody rituximab in mice xenografted with the human RL lymphoma model. Liposomal encapsulation also allowed a 2-fold reduction in the induction of proinflammatory cytokines by LPS. Mice receiving an intravenous administration demonstrated a significant increase of neutrophils, monocytes and macrophages at the tumor site as well as an increase of macrophages in spleen. Further, we chemically detoxified LPS to obtain MP-LPS that was associated with a 200-fold decrease in the induction of proinflammatory cytokines. When encapsulated in a clinically approved liposomal formulation, toxicity, notably pyrogenicity (10-fold), was limited while the antitumor activity and immunoadjuvant effect were maintained. This improved tolerance profile of liposomal MP-LPS was associated with the preferential activation of the TLR4-TRIF pathway. Finally, in vitro studies demonstrated that stimulation with encapsulated MP-LPS reversed the polarization of M2 macrophages towards an M1 phenotype, and a phase 1 trial in healthy dogs validated its tolerance upon systemic administration up to very high doses (10µg/kg). Altogether, our results demonstrate the strong therapeutic potential of MPLPS formulated in liposomes as a systemically active anticancer agent, supporting its evaluation in patients with cancer. [ABSTRACT FROM AUTHOR]

Bacterial lipopolysaccharides (LPS) are potent innate immunostimulants targeting the Toll-like receptor 4 (TLR4), an attractive and validated target for immunostimulation in cancer therapy. Although LPS possess anti-tumor activity, toxicity issues prevent their systemic administration at effective doses in humans. We first demonstrated that LPS formulated in liposomes preserved a potent antitumor activity per se upon systemic administration in syngeneic models, and significantly enhance the antitumor activity of the anti-CD20 antibody rituximab in mice xenografted with the human RL lymphoma model. Liposomal encapsulation also allowed a 2-fold reduction in the induction of pro-inflammatory cytokines by LPS. Mice receiving an intravenous administration demonstrated a significant increase of neutrophils, monocytes and macrophages at the tumor site as well as an increase of macrophages in spleen. Further, we chemically detoxified LPS to obtain MP-LPS that was associated with a 200-fold decrease in the induction of proinflammatory cytokines. When encapsulated in a clinically approved liposomal formulation, toxicity, notably pyrogenicity (10-fold), was limited while the antitumor activity and immunoadjuvant effect were maintained. This improved tolerance profile of liposomal MP-LPS was associated with the preferential activation of the TLR4-TRIF pathway. Finally, in vitro studies demonstrated that stimulation with encapsulated MP-LPS reversed the polarization of M2 macrophages towards an M1 phenotype, and a phase 1 trial in healthy dogs validated its tolerance upon systemic administration up to very high doses (10µg/kg). Altogether, our results demonstrate the strong therapeutic potential of MPLPS formulated in liposomes as a systemically active anticancer agent, supporting its evaluation in patients with cancer.

Introduction: COX-2 inhibition in pro-tumoral M2 polarization of Tumor-Associated Macrophages (TAMs) underscore the improved prognosis and response to cancer therapy. Thus, etoricoxib, a COX-2 inhibiting NSAID drug is highly effective against tumorigenesis, but its compromised solubility and associated hepatotoxicity, and cardiotoxicity limit its clinical translation. Objective: In view of the consequences, the proposed study entails the development of a liposomal formulation for etoricoxib and evaluates its anticancer potential. Methods and Result: Etoricoxib loaded liposome was prepared by thin layer hydration method and characterized as a nearly monodisperse system with particle size (91.64 nm), zeta potential (-44.5 mV), drug loading (17.22%), and entrapment efficiency (94.76%). The developed formulation was administered subcutaneously into the orthotopic 4T1/Balb/c mice model. Its treatment significantly reduced tumor size and skewed M2 polarization of TAMs to a greater extent against free etoricoxib. Furthermore, Tumor tissues analyzed through immunoblotting study confirmed the reduction in Akt phosphorylation at Thr308 residue and pro-tumoral VEGF, MMP-9, and MMP-2 proteins; Moreover, histology studies and microCT analysis of bones revealed the enhanced anti-metastatic potential of etoricoxib delivered through developed formulation against free etoricoxib. Conclusion: As an epilogue, the developed formulation efficiently delivers poorly soluble etoricoxib, enhances its therapeutic potential as an anti-tumor and anti-metastatic agent, and directs explorative research for clinical translation. [ABSTRACT FROM AUTHOR]

Nanomedicines have revolutionized the treatment of certain types of cancer, as is the case of doxil, liposomal formulation with doxorubicin encapsulated, in the treatment of certain types of ovarian cancer, AIDS-related Kaposi sarcoma, and multiple myeloma. These nanomedicines can improve the performance of conventional chemotherapeutic treatments, with fewer side effects and better efficiency against cancer. Although liposomes have been used in some formulations, different nanocarriers with better features in terms of stability and adsorption capabilities are being explored. Among the available nanoparticles in the field, mesoporous silica nanoparticles (MSNP) have attracted great attention as drug delivery platforms for the treatment of different diseases. Here, a novel formulation based on MSNP loaded with a potent antitumor prodrug that works in vitro as well as in a clinically evaluated liposomal formulation has been developed. This novel formulation shows excellent prodrug encapsulation efficiency and effective release of the anticancer drug only under certain stimuli typical of tumor environments. This behavior is of capital importance for translating this nanocarrier to the clinic in the near future. [ABSTRACT FROM AUTHOR]

Purpose: developing customized titanium specimens, with innovative surfaces, is a suitable strategy to overcome implant failure. Additionally, a faster and efficient osteogenic commitment assists tissue regeneration. To investigate the interplay between inflammation and differentiation upon implantation, Dental Pulp Stem Cells (DPSCs) were cultured on 3D-printed titanium owning an internal open cell form, administering osteogenic factors by a liposomal formulation (LipoMix) compared to traditional delivery of differentiation medium (DM)., Materials and Methods: osteogenic differentiation was evaluated by western blot, by measuring β1 integrin expression, and by and real-time RT-PCR, by measuring SP7 and Collagen I gene expression; while.angiogenesis was characterized by measuring VEGF secretion levels. Matrix mineralization was assessed by means of Alizarin Red Staining, cell adhesion and inflammation responses through western blot, enzymatic and ELISA assays evaluating Nrf2 expression, catalase activity and Prostaglandin E2 secretion, respectively., Results: LipoMix enhances cell proliferation and adhesion, as revealed by increased integrin β1 expression. Mineralized matrix deposition, SP7 gene expression, Collagen I release and Alkaline Phosphatase activity appear increased in LipoMix condition. Additionally, the redox-sensitive transcription factor Nrf2 is overexpressed at the earliest experimental times, triggering the catalase activity., Conclusions: data reported confirm that internal topography and post-production treatments on titanium surfaces dynamically and positively condition the DPSC progress towards the osteogenic phenotype, moreover, the combination with LipoMix fastens the positive modulation of inflammation under osteogenic conditions. Therefore, the development of customized surfaces along with the administration of differentiating factors enclosed in a liposomal delivery system, could represent a promising and innovative tool in regenerative dentistry.

Systemically vaccinated individuals against COVID-19 and influenza may continue to support viral replication and shedding in the upper airways, contributing to the spread of infections. Thus, a vaccine regimen that enhances mucosal immunity in the respiratory mucosa is needed to prevent a pandemic. Intranasal/pulmonary (IN) vaccines can promote mucosal immunity by promoting IgA secretion at the infection site. Here, we demonstrate that an intramuscular (IM) priming-IN boosting regimen with an inactivated influenza A virus adjuvanted with the liposomal dual TLR4/7 adjuvant (Fos47) enhances systemic and local/mucosal immunity. The IN boosting with Fos47 (IN-Fos47) enhanced antigen-specific IgA secretion in the upper and lower respiratory tracts compared to the IM boosting with Fos47 (IM-Fos47). The secreted IgA induced by IN-Fos47 was also cross-reactive to multiple influenza virus strains. Antigen-specific tissue-resident memory T cells in the lung were increased after IN boosting with Fos47, indicating that IN-Fos47 established tissue-resident T cells. Furthermore, IN-Fos47 induced systemic cross-reactive IgG antibody titers comparable to those of IM-Fos47. Neither local nor systemic reactogenicity or adverse effects were observed after IN delivery of Fos47. Collectively, these results indicate that the IM/IN regimen with Fos47 is safe and provides both local and systemic anti-influenza immune responses.

This review examined a collection of studies regarding the molecular properties of some polyene antibiotic molecules as well as their properties in solution and in particular environmental conditions. We also looked into the proposed mechanism of action of polyenes, where membrane properties play a crucial role. Given the interest in polyene antibiotics as therapeutic agents, we looked into alternative ways of reducing their collateral toxicity, including semi-synthesis of derivatives and new formulations. We follow with studies on the role of membrane structure and, finally, recent developments regarding the most important clinical applications of these compounds.

Control of free or unentrapped drug is one of the key quality attributes for liposomal drug delivery systems. Conventional methodologies for estimating unentrapped drug in liposomal formulations require prior separation, which are time-consuming and complex. There is a need for a quick in-process analytical technique, which can enable monitoring of drug loading during various stages of product development and manufacturing. A novel simple and rapid TLC procedure was developed for evaluating entrapment efficiency in liposomal formulations. The method is based on differential radial migration of free and entrapped drug on silica gel TLC plates. The method can be employed either as a simple visual qualitative tool in the early screening studies or in a semi-quantitative mode for detection of free and unentrapped drugs. In case of doxorubicin hydrochloride, a deep-red coloured molecule, the method enabled free drug detection up to the levels as low as 2.5%. This method precluded the need of developing the plate further with the mobile phase. The method was used successfully in product development or as an in-process monitoring tool. The method's potential for characterizing entrapment efficiency was evaluated for less intensely coloured or UV absorbing drug candidates such as amphotericin B liposome and curcumin liposome. The preliminary results post derivatization with ninhydrin reagent or visualization under UV light indicated applicability of technique in general for liposomal delivery systems of various other drugs. According to the best of the author's knowledge, there has been no reports on the evaluation of drug entrapment using such TLC based technique so far. [ABSTRACT FROM AUTHOR]

Topical liposomal drug formulations containing AS1411-aptamer conjugated liposomes were designed to deliver in a sustained way the 5-fluorouracil to the tumor site but also to increase the compliance of patients with basal cell carcinoma. The 5-fluorouracil penetrability efficiency through the Strat-M membrane and the skin irritation potential of the obtained topical liposomal formulations were evaluated in vitro and the Korsmeyer Peppas equation was considered as the most appropriate to model the drug release. Additionally, the efficiency of cytostatic activity for targeted antitumor therapy and the hemolytic capacity were performed in vitro. The obtained results showed that the optimal liposomal formulation is a crosslinked gel based on sodium alginate and hyaluronic acid containing AS1411-aptamer conjugated liposomes loaded with 5-fluorouracil, which appeared to have favorable biosafety effects and may be used as a new therapeutic approach for the topical treatment of basal cell carcinoma.

Although several liposomal drugs, including liposomal doxorubicin, have been approved, the etiology of the pathological responses caused by their physicochemical properties remains unknown. Herein, we investigated the pathological changes in the liver and the gallbladder of dogs following a single injection of liposomal doxorubicin (1 or 2.5 mg/kg) or an empty liposomal formulation (i.e., liposomal formulation without doxorubicin, ca. 21 mg/kg as lipid content). Injection of liposomal doxorubicin or the empty liposomal formulation induced hemorrhagic changes in the liver and the gallbladder. These changes were accompanied by minimal cellular infiltration with no obvious changes in the blood vessels. As there were no differences in the incidence and severity of hemorrhage between the groups administered comparable amounts of total lipid, the physicochemical properties of the liposomal formulation rather than an active pharmacological ingredient, doxorubicin, were associated with the hemorrhagic changes. Furthermore, decreased cytoplasmic granules with low electron density in mast cells beneath the endothelium of the hepatic vein were observed in the liver of dogs treated with liposomal doxorubicin or empty liposomal formulation. Injection of compound 48/80, a histamine releaser induced comparable hemorrhage in dogs, implying that hemorrhage caused by injection of liposomal doxorubicin or the empty liposomal formulation could be attributed to the histamine released from mast cells. The absence of similar hemorrhagic lesions in other species commonly used in toxicology studies (i.e., rats and monkeys), as well as humans, is due to the lack of mast cells beneath the endothelium of the hepatic vein in these species. [ABSTRACT FROM AUTHOR]

Identifying the critical process parameters (CPPs) of a complex drug product manufacture and the associated impact on critical quality attributes (CQAs) is essential to the development and quality control of both new and generic drugs. AmBisome, a liposomal amphotericin B (AMB) macrolide antibiotic widely adopted as an important antifungal drug product, was used as a model complex drug product in the current study. This study investigated how multi-step production approaches and related manufacturing conditions may affect essential physico-chemical and toxicological properties of the final drug product. A key challenge in the manufacture and analysis of liposomal AMB was the drug substance's propensity to aggregate, with associated poor solubility in water and organic solvents. This study identified three key CPPs in a four step manufacturing process: (i) proper acidification during formation of the drug-lipid complexes (Step 1), (ii) liposome heat curing following liposomal particle sizing (Step 3), and (iii) flash-freezing at the initial stages of the lyophilization cycle (Step 4). Over-acidification led to rapid degradation of the drug, whereas under-acidification hampered full solubilization and formation of the soluble drug-lipid complexes. Extended heat treatment of the formed liposomes at 65 °C, just above the lipid phase transition temperature, brought dramatic changes in the aggregated state and/or packing of the drug in the liposomal bilayer, as followed by the complex changes in the UV/Vis spectra. Such thermal conditioning resulted in a five- to ten-fold reduction in the in-vitro toxicity of the drug product, bringing it close to the values for AmBisome used as control and measured by the RBC assay. Finally, flash-freezing conditions during lyophilization was critical to prevent aggregation and maintaining the 80–120 nm liposome size when reconstituted. Our research found that changes in the amphotericin's UV/Vis spectra were a sensitive CQA measure and provided a set of quantitative parameters for a facile non-destructive process monitoring in-situ , as well as for comparison of the quality of final formulations. [ABSTRACT FROM AUTHOR]

Developing nanostructures for cancer treatment is growing significantly. Liposomal doxorubicin is a drug that is used in the clinic and represents a lot of benefits over doxorubicin. The development of multifunctional liposomes with different cancer treatment capability enables broader applications of doxorubicin chemotherapy. Many efforts were carried to prepare more effective liposomal formulation through loading gold nanoparticles (GNPs) in the formulation. Here, GNPs with an average size of 6 nm were loaded in liposomal formulation alongside doxorubicin. The hydrodynamic diameter of final formulation was 177.3 ± 33.9 nm that in comparison with liposomes without GNPs (112.5 ± 10.3 nm), GNPs‐loaded liposomes showed the bigger hydrodynamic diameter. GNPs‐loaded liposomes are slightly positively charged (4.4 ± 1.1 mV), while liposomes without loading the GNPs were negatively charged (−18.5 ± 1.6 mV). Doxorubicin was loaded in this formulation through active loading technique. Doxorubicin loading efficiency in gold‐loaded liposomes is slightly lesser than liposomes without GNPs, but still considerably high in comparison to passive loading techniques. [ABSTRACT FROM AUTHOR]

The role of bilayerd vesicles as efficient carriers for drugs, vaccines, diagnostic agents and other bioactive agents have led to a rapid advancement in the liposomal drug delivery system. Moreover, the site prevention and site-specific drug targeting therapy could be achieved by formulating a liposomal product, so as to reduce the cytotoxicity of many potent therapeutic agents. This article is intended to provide an overview of liposomal drug delivery system. It has focused on the factors affecting the behavior of the liposomes in the biological surroundings. Various aspects related to mechanism of liposome formation, characterization and stability of the liposomal drug product were also discussed in the article. Liposomes can be used as a therapeutic tool in the fields like tumor targeting, genetic transfer, immunomodulation, skin and topical therapy. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that fat accumulation in bone cells is detrimental to bone mass. Both adipocytes and osteoblasts are derived from common multipotent mesenchymal stem cells (MSCs) and hence the presence of fat may increase adipocyte proliferation, differentiation and fat accumulation while inhibiting osteoblast differentiation and bone formation. Lipids are common constituents in supramolecular vesicles (e.g., micelles or liposomes) that serve as drug delivery systems. Liposomal formulations such as Meriva® were proven to decrease joint pain and improve joint function in osteoarthritis (OA) patients. In this study, we evaluated how lipid types and liposomal formulations affect osteoblast behavior including cell viability, differentiation, mineralization and inflammation. Various liposomal formulations were prepared using different types of lipids, including phosphatidylcholine (PC), 1,2-dioleoyl-sn-glycero-3-phospho-ethanolamine (DOPE), cholesterol (Chol), 3p-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol hydrochloride (DC-cholesterol HCl), and 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) to investigate the impact on osteoblast differentiation and inflammation. The results indicated that cationic lipids, DC-cholesterol and DOTAP, presented higher dose-dependent cytotoxicity and caused high level of inflammatory responses. Due to the natural properties of lipids, all the lipids can induce lipid droplet formation in osteoblasts but the level of lipid droplet accumulation was different. In comparison with cationic lipids, neutral lipids induced less adiposity, and maintained high osteoblast mineralization. Similar to previous researches, we also confirmed an inverse relationship between lipid droplet formation and osteoblast mineralization in 7F2 mouse osteoblasts. Importantly, PC containing liposomes (PC only and PC/DOTAP) suppressed IL-1β-induced gene expression of COX-2 and MMP-3 but not Chol/DOTAP liposomes or DC-Chol/DOPE liposomes. Taken together, we suggested that PC contained liposomes could provide the best liposomal formulation for the treatment of bone diseases. [ABSTRACT FROM AUTHOR]

Shear stress could be considered in the context of cellular uptake and cell-killing efficiency. Thus, mimicking the dynamic characteristics of in vivo environment is important in targeted drug delivery. We investigated the intracellular uptake and cell-killing efficiency of doxorubicin (DOX) in a free and liposomal form (Doxil ® ) under biomimetic shear stress to mimic in vivo environment. In this dynamic environment, cells demonstrated significantly higher fluorescence intensity than that of the static environment, and fluorescence microscopy images indicated increased intracellular uptake of DOX in the presence of fluidic shear stress. In cells treated with free DOX and liposomal Doxil ® , cell-killing efficiency was affected by shear stress. Taken together, shear stress, affecting drug uptake and cell-killing efficiency, is important in intracellular drug targeting. [ABSTRACT FROM AUTHOR]