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Drug delivery systems are believed to increase pharmaceutical efficacy and the therapeutic index by protecting and stabilizing bioactive molecules, such as protein and peptides, against body fluids’ enzymes and/or unsuitable physicochemical conditions while preserving the surrounding healthy tissues from toxicity. Liposomes are biocompatible and biodegradable and do not cause immunogenicity following intravenous or topical administration. Still, their most important characteristic is the ability to load any drug or complex molecule uncommitted to its hydrophobic or hydrophilic character. Selecting lipid components, ratios and thermo-sensitivity is critical to achieve a suitable nano-liposomal formulation. Nano-liposomal surfaces can be tailored to interact successfully with target cells, avoiding undesirable associations with plasma proteins and enhancing their half-life in the bloodstream. Macropinocytosis-dynamin-independent, cell-membrane-cholesterol-dependent processes, clathrin, and caveolae-independent mechanisms are involved in liposome internalization and trafficking within target cells to deliver the loaded drugs to modulate cell function. A successful translation from animal studies to clinical trials is still an important challenge surrounding the approval of new nano-liposomal drugs that have been the focus of investigations. Precision medicine based on the design of functionalized nano-delivery systems bearing highly specific molecules to drive therapies is a promising strategy to treat degenerative diseases.

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.

•This is the first-in-human trial of both FMP013 and the ALFQ adjuvant.•The vaccine evinced significant humoral and cell mediated immunogenicity.•The vaccine demonstrated an acceptable safety profile.•The results of this trial have led to an efficacy trial using CHMI. The global burden of malaria remains substantial. Circumsporozoite protein (CSP) has been demonstrated to be an effective target antigen, however, improvements that offer more efficacious and more durable protection are still needed. In support of research and development of next-generation malaria vaccines, Walter Reed Army Institute of Research (WRAIR) has developed a CSP-based antigen (FMP013) and a novel adjuvant ALFQ (Army Liposome Formulation containing QS-21). We present a single center, open-label, dose-escalation Phase 1 clinical trial to evaluate the safety and immunogenicity of the FMP013/ALFQ malaria vaccine candidate. In this first-in-human evaluation of both the antigen and adjuvant, we enrolled ten subjects; five received 20 μg FMP013 / 0.5 mL ALFQ (Low dose group), and five received 40 μg FMP013 / 1.0 mL ALFQ (High dose group) on study days 1, 29, and 57. Adverse events and immune responses were assessed during the study period. The clinical safety profile was acceptable and there were no serious adverse events. Both groups exhibited robust humoral and cellular immunological responses, and compared favorably with historical responses reported for RTS,S/AS01. Based on a lower reactogenicity profile, the 20 μg FMP013 / 0.5 mL ALFQ (Low dose) was selected for follow-on efficacy testing by controlled human malaria infection (CHMI) with a separate cohort. Trial Registration:Clinicaltrials.gov Identifier NCT04268420 (Registered February 13, 2020)

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.

Despite the clinical efficacy of current intramuscular influenza vaccines in reducing the severity of seasonal infection, they exhibit limited induction of mucosal immunity, which is essential for preventing viral transmission. In addition, intranasal vaccination can induce superior mucosal immunity, enhancing clinical efficacy and reducing transmission, and its self-boosting potential may improve coverage in older adults and those with mobility limitations. We developed Lipo-1V270, a liposomal nanoparticle formulation of the synthetic TLR7 agonist 1V270 using 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and cholesterol for mucosal vaccine delivery. In vitro immune stimulation and in vivo immunogenicity were evaluated using intramuscular and intranasal routes in mouse models, including a heterologous prime-boost regimen with inactivated influenza A virus [IIAV, A/California/04/2009 (H1N1)pdm09] adjuvanted monophosphoryl lipid A (MPLA) priming. In vitro analysis showed that Lipo-1V270 exhibited attenuated innate immune potency compared to unformulated 1V270. However, in vivo co-administration of Lipo-1V270 with IIAV significantly enhanced antigen-specific IgG1 and IgG2a responses. Subsequently, intranasal boosting with Lipo-1V270, following intramuscular priming with IIAV adjuvanted with MPLA - a component included in FDA-approved vaccines - elicited robust influenza-hemagglutinin (HA)-specific mucosal IgA and IgG responses in nasal wash. This heterologous prime-boost regimen also induced strong splenic T-cell responses and HA-specific IgG and IgA antibodies in nasal wash without causing significant weight loss for 7 days post-boost in immunized mice. Intranasal administration of Lipo-1V270 in a heterologous prime-boost vaccination regimen effectively enhances mucosal immunity against influenza virus infection, with an acceptable innate immune-mediated adverse effects profile. This strategy may be applicable to vaccines against other respiratory infectious diseases. •Vaccination with inactivated Influenza A virus (IIAV) adjuvanted with liposomal formulation of small molecule TLR7 ligand induced both Th1 and Th2 biased responses.•A heterologous immunization with MPLA prime and intranasal Lipo-1 V270 with IIAV boost strategy improved mucosal anti-influenza immune response.•Vaccination with Lipo-1V270 adjuvanted vaccine did not show immune mediated systemic adverse effects.

Dermatological diseases pose a significant challenge due to their chronic nature, complex pathophysiology, and the need for effective, patient-friendly treatments. Recent advancements in liposomal and gel-based formulations have played a crucial role in improving drug delivery, therapeutic efficacy, and patient compliance. Liposomal formulations have garnered considerable attention in dermatology due to their ability to encapsulate both hydrophilic and lipophilic compounds, enabling controlled drug release and enhanced skin penetration. However, challenges such as formulation complexity, stability issues, and regulatory constraints remain. Similarly, gel-based formulations are widely used due to their ease of application, biocompatibility, and ability to retain active ingredients. However, they also face limitations, including restricted penetration depth, susceptibility to microbial contamination, and challenges in achieving sustained drug release. The integration of liposomal and gel-based technologies offers a promising strategy to overcome current challenges and optimize dermatological drug delivery. This review explores both well-established therapies and recent innovations, offering a comprehensive overview of their applications in the treatment of prevalent dermatological conditions. Ultimately, continued research is essential to refine these formulations, expanding their clinical utility and enhancing therapeutic effectiveness in dermatology.

To determine the effectiveness of subconjunctival application of a novel sirolimus liposomal formulation for the treatment of dry eye. A randomized, triple-blind, Phase II clinical trial. Thirty-eight eyes of 19 patients were included. Nine patients (18 eyes) assigned to the sham group (Sham) and 10 patients (20 eyes) to sirolimus-loaded liposomes group (Sirolimus). The treatment group received three doses of subconjunctival liposome-encapsulated sirolimus and the sham group received three doses of liposomal suspension without sirolimus. Subjective (Ocular Surface Disease Index, OSDI) and measured (corrected distance visual acuity, conjunctival hyperemia, tear osmolarity, Schirmer's test, corneal/conjunctival staining and matrix metalloproteinase-9) variables were measured. Sirolimus-entrapped liposomes-treated group OSDI scores changed from 62.19 (± 6.07) to 37.8 (± 17.81) (p=0.0024), and conjunctival hyperemia from 2.0 (± 0.68) to 0.83 (± 0.61) (p<0.0001); Sham group with OSDI scores from 60.02 (± 14.2) to 36.02 (± 20.70) (p=0.01), and conjunctival hyperemia from 1.33 (± 0.68) to 0.94 (± 0.87) (p=0.048). All the other evaluated outcomes only showed significant differences in the sirolimus group: corneal/conjunctival staining score (p=0.0015), lipid layer interferometry (p=0.006), and inferior meibomian gland dropout (p=0.038). No local or systemic adverse effects regarding the medication itself were reported, and the administration route was well accepted. Our findings suggest that sub-conjunctival sirolimus-loaded liposomes are effective in reducing both signs and symptoms of dry eye in patients with poorly controlled moderate-to-severe DED, while avoiding other topical administration adverse effects. Further investigation with a larger sample size is required to determine long-term effects.

IntroductionCOX-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.ObjectiveIn view of the consequences, the proposed study entails the development of a liposomal formulation for etoricoxib and evaluates its anticancer potential.Methods and ResultEtoricoxib 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.ConclusionAs 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.

Over the last three decades many first-generation nanomedicines have successfully entered routine clinical use and it is now important for medicines regulatory agencies to consider the mechanisms needed to ensure safe introduction of 'follow-on nanomedicine products, 'nanosimilars . Moreover, drug regulators need to ensure that 'next -generation nanomedicines enter clinical development and consequently the market in a safe and timely way for the benefit of public health. Here we review recent European Medicines Agency activities that relate to the effective development and evaluation of nanomedicine products while keeping patient and consumer safety at the forefront.

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/m 2 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.