Liposomal Delivery System Research Articles

Liposomal Drug Delivery against Helicobacter pylori Using Furazolidone and N-Acetyl Cysteine in Augmented Therapy.

Helicobacter pylori (H. pylori) infection is a significant global health concern, affecting approximately 50% of the world's population and leading to gastric ulcers, gastritis, and gastric cancer. The increase in antibiotic resistance has compromised the efficacy of existing therapeutic regimens, necessitating novel approaches for effective eradication. This study aimed to develop a targeted liposomal drug delivery system incorporating furazolidone and N-acetylcysteine (NAC) to enhance mucopenetration and improve Helicobacter pylori eradication. Liposomes were formulated with furazolidone, NAC, and Pluronic F-127 using a modified reverse-phase evaporation technique. The formulations were categorized based on charge as neutral, negative, and positive and tested for mucopenetration using a modified silicon tube method with coumarin-6 as a fluorescent marker. The encapsulation efficiency and particle size were analyzed using HPLC and an Izon q-nano particle size analyzer. The results indicated that charged liposomes showed a higher encapsulation efficiency than neutral liposomes with Pluronic F-127. Notably, combining furazolidone with 1% NAC achieved complete eradication of H. pylori in 2.5 h, compared to six hours without NAC. The findings of this study suggest that incorporating NAC and Pluronic F-127 into liposomal formulations significantly enhances mucopenetration and antimicrobial efficacy.

Isolation, Purification of Phenolic Glycoside 1 from Moringa oleifera Seeds and Formulation of Its Liposome Delivery System.

In this study, N, N '-bis {4- [(α-L- rhamnosyloxy) benzyl]} thiourea (PG-1), a phenolic glycoside compound was purified from Moringa seed. The PG-1 has attracted extensive attention due to its anti-cancer, antioxidant, anti-inflammatory and hypoglycemic properties. However, some of its physicochemical properties such as oral bioavailability has not been studied. Herein, a highly purified PG-1 was extracted and incorporated in multiple layered liposomes (PG-1-L) to avoid its burst release and enhance oral bioavailability. After appropriate characterization, it was discovered that the obtained PG-1-L was stable, homogeneous and well dispersed with the average particle size being 89.26 ± 0.23 nm. Importantly, the in vitro release and in vivo oral bioavailability of PG-1-L were significantly improved compared with PG-1. In addition, MTT results showed that compared with the free PG-1, PG-1-L displayed obvious inhibitory effect on the HepG2 cells, while the inhibitory effect on healthy non-malignant 3T6 and LO-2 cells was not significant, indicating that PG-1-L had high safety. In conclusion, PG-1-L can be used as a promising delivery system and an ideal novel approach to improve the oral bioavailability and anticancer activity of PG-1.

Preparation of double-loaded bitter ginseng derivative B21–DOX liposomes co-modified with SP94 and BR2 ligand and its in vitro anti-hepatocarcinogenic effect

Aim To construct a novel liposomal drug delivery system co-modified with SP94 and BR2 ligands, encapsulating both the bitter ginseng derivative B21 and doxorubicin (DOX), to achieve superior anti-tumour efficacy and reduced toxic side effects. Methods Liposomes were prepared using an organic phase reaction method, with B21 encapsulated in the lipid phase and DOX in the aqueous phase. The liposomes were further modified with SP94 and BR2 peptides. The characterisations, cytotoxicity, and in vitro targeting effects were assessed through various methods including ultraviolet spectrophotometry, high-performance liquid chromatography, nano-size analysis, ultrafiltration centrifugation, dialysis, transmission electron microscopy, flow cytometry, Methylthiazolyldiphenyl-tetrazolium bromide assay, confocal laser scanning microscopy, transwell assay, and tumorsphere assay. Results SP94/BR2-B21/DOX-LP liposomes were spherical with an average diameter of 120.87 ± 1.00 nm, a polydispersity index (PDI) of 0.223 ± 0.006, and a surface charge of −23.1 ± 1.27 mV. The encapsulation efficiencies for B21 and DOX were greater than 85% and 97% (mg/mg), respectively. The results indicated that SP94/BR2-B21/DOX-LP exhibited enhanced targeting and cytotoxicity compared to single-ligand modified and unmodified liposomes, with the combined encapsulation of B21 and DOX showing synergistic anti-hepatocarcinogenic effects. Conclusion SP94/BR2-B21/DOX-LP liposomes represent a promising targeted drug delivery system for hepatocellular carcinoma, offering improved membrane penetration, enhanced therapeutic efficacy, and reduced systemic toxicity.

Construction and evaluation of liposomal drug delivery system for an ALK/HDACs dual-targeted inhibitor with sustained release and enhanced antitumor effect.

ALK/HDACs dual target inhibitor (PT-54) was a 2,4-pyrimidinediamine derivative synthesized based on the pharmacophore merged strategy that inhibits both anaplastic lymphoma kinase (ALK) and histone deacetylases (HDACs), which has demonstrated significant efficacy in treating multiple cancers. However, its poor solubility in water limited its clinical application. In this study, we prepared PT-54 liposomes (PT-54-LPs) by the membrane hydration method to overcome this defect. The encapsulation efficiency (EE) and particle size were used as evaluation indicators to explore the preparation conditions of PT-54-LPs. The morphology, particle size, EE, drug loading content (DLC), drug release properties, and stability of PT-54-LPs were further investigated. In vitro drug release studies showed that PT-54-LPs exhibited significant slow-release properties compared with free PT-54. PT-54-LPs also showed better tumor inhibitory effects than free PT-54 without significant adverse effects. These results suggested that PT-54-LPs displayed sustained drug release and significantly improved the tumor selectivity of PT-54. Thus, PT-54-LPs showed significant promise in enhancing anticancer efficiency.

In Vitro Antioxidant Activity of Liposomal Formulations of Sea Buckthorn and Grape Pomace.

This study evaluated the impact of the encapsulation of sea buckthorn and grape pomace extracts in liposomal formulations on the retention and release of bioactive compounds and their antioxidant activity. The profile and composition of lipophilic extracts of sea buckthorn and hydrophilic extracts of grape pomace were analyzed. Encapsulation efficiency, retention rate, and the content of bioactive compounds encapsulated in liposomal formulations prepared in two media-water and ethanol-were evaluated. The encapsulation efficiency varied between 84 and 90%, indicating the superior encapsulation of the bioactive compounds. The retention rate varied between 79 and 86%, which indicated the stability of the liposome-encapsulated compounds over time. The antioxidant activity of the encapsulated samples was determined in vitro, under the conditions of gastric (pH 1.8) and intestinal (pH 8.2) digestion, in relation to the non-encapsulated extracts. The antioxidant activity of both liposomal formulations was higher than that of the nonencapsulated extracts during gastric digestion. Moreover, an increase over time in the antioxidant activity, expressed as % DPPH inhibition, was observed for all samples, with around 90% DPPH inhibition for non-encapsulated extracts and 92% for the encapsulated extracts, demonstrating the stability of bioactive compounds in acidic pH. Oppositely, when exposed to intestinal simulated digestion (alkaline pH), the antioxidant activity decreased over time to around 24% DPPH inhibition for both encapsulated and nonencapsulated extracts. These results provide a foundation for the further development and application of liposomal delivery systems in functional foods.

Preparation, characterization, in vitro and in vivo studies of liposomal berberine using novel natural Fiber Interlaced Liposomal technology

Berberine hydrochloride (BBR), used in various traditional medicinal practices, has a variety of pharmacological effects. It is a plant-derived quaternary isoquinoline alkaloid with a low water solubility and can be used in the treatment of various conditions. However, the therapeutic use of BBR has been compromised because of its hydrophobic characteristics, in addition to its low stability and poor bioavailability. To overcome these drawbacks of BBR’s oral bioavailability, technologies like liposomal delivery systems have been developed to ensure enhanced absorption. But conventional liposomes have low physical and chemical stability due to delicate liposomal membranes, peroxidation and rapid clearance from the bloodstream. Surface modification of liposomes could be a solution and creating a liposome with plant-based fibers as surface material will provide enhanced stability, aqueous solubility and protection against degradation. Consequently, the aim of this study is to create and describe a Fiber Interlaced Liposome™ (FIL) as a vehicle for an enhanced bioavailability platform for BBR and other biomolecules. This optimised FIL-BBR formulation was analysed for its structural and surface morphological characteristics by using FTIR, SEM, TEM, XRD, zeta potential and DSC. Encapsulation efficiency, stability, and sustained release studies using an in vitro digestion model with simulated gastric and intestinal fluids were also examined. FIL formulation showed a sustained release of BBR at 59.03 % as compared to the unformulated control (46.73 %) after 8 h of dialysis. Furthermore, the FIL-BBR demonstrated enhanced stability in the simulated gastric fluid (SGF) in addition to a more sustained release in the simulated intestinal fluid (SIF). The efficacy of FIL-BBR were further anlaysed by an in vivo bioavailability study using male Wistar rats and it demonstrated a 3.37−fold higher relative oral bioavailability compared to the unformulated BBR. The AUC 0-t for BBR in FIL-BBR was 1.38 ng.h/mL, significantly greater than the unformulated BBR (0.41 ng.h/mL). Similarly, the Cmax for BBR in FIL-BBR (50.98 ng/mL) was discovered to be far greater than unformulated BBR (15.54 ng/mL) after the oral administration. These findings imply that fruit fiber based liposomal encapsulation improves the stability and slows down BBR release, which could be advantageous for applications requiring a higher bioavailability and a more sustained release.

Influence of archaeal lipids isolated from Aeropyrum pernix K1 on physicochemical properties of sphingomyelin-cholesterol liposomes

We investigated the influence of archaeal lipids (C25,25) isolated from thermophilic archaeon Aeropyrum pernix K1 on physicochemical properties of liposomes comprised of egg sphingomyelin (SM) and cholesterol (CH) using fluorescence emission anisotropy, calcein release studies, dynamic light scattering, transmissive electron microscopy and phase analysis light scattering. The 2 mol% addition of archaeal lipids enabled formation of small unilamellar vesicles by sonication while also having significant effect on reducing mean size, polydispersity index and zeta potential of C25,25/SM/CH vesicles. Increasing the ratio of C25,25 lipids in mixture of C25,25/SM/CH decreased lipid ordering parameter in dose dependent manner at different temperatures. We also demonstrated that adding 15 mol% C25,25 to SM/CH mixture will cause it to notably interact with fetal bovine serum which could make them a viable alternative adjuvant to synthetic ether-linked lipids in development of advanced liposomal vaccine delivery systems. The prospect of combining the proven strengths of SM/CH mixtures with the unique properties of C25,25 opens exciting possibilities for advancing drug delivery technologies, promising to yield formulations that are both highly effective and adaptable to a range of therapeutic applications.

Advancements in Natural Alkaloid-Loaded Drug Delivery Systems for Enhanced Peptic Ulcer Treatment: A Review

Abstract: Peptic ulcers, which damage the gastrointestinal tract lining, are a significant global health issue. The traditional approaches to treating peptic ulcers have poor bioavailability, unstable formulations, and undesirable side effects. Natural alkaloids have garnered increased interest as potential therapeutic agents in recent years due to their diverse pharmacological actions and decreased toxicity profiles. This manuscript summarizes recent progress in natural alkaloids for peptic ulcer treatment, highlighting new drug delivery methods. Natural alkaloids, originating from different plants, have anti-inflammatory, antioxidant, and antibacterial properties, potentially accelerating the healing of peptic ulcers. Moreover, medicines don't always function properly because they degrade too fast, don't dissolve well, and have other problems, such as insufficient bioavailability. Creative liposome delivery systems, microspheres, nanocarriers, and other customized delivery strategies have shown promise in overcoming these barriers. By distributing the medication gradually and precisely, these innovative techniques improve the medication and effectiveness at the ulcer site. As a result, natural ingredients work better and provide better treatment results.

Application of Nanotechnology for Herbal Medicine Development: A Review

Background: Herbal medicines have been extensively used to treat diseases since the prehistoric era, but written records date back more than 5,000 years only. All civilizations developed their knowledge of herbal medicines in a well-ordered system, such as Ayurveda, Unani, Traditional Chinese Medicine, etc. The interest in traditional medicine declined after the discovery of modern medicine. However, in the 21st century, herbal medicines are staging a comeback as the dangers and limitations of modern medicine have become more apparent and herbal medicines are viewed as a balanced and moderate approach to healing. Methods: This review includes the nanoformulations of phytoconstituents and extract. Advancements in analysis and clinical research prove the efficacy of nano-herbal medicines in preventing and treating diseases. This review is mostly about how nanotechnology can be used to help herbal medicines work better. Result: The major problems with herbal medicines are their poor solubility and stability. New technological advancements are capable of removing the problems associated with herbal medicine. Novel drug delivery systems such as microemulsion, liposome, niosome, and nano-drug delivery systems are used to enhance the safety and efficacy of herbal medicines. Conclusion: Nanotechnology has significant merit for herbal medicines, such as improving solubility, bioavailability, pharmacological activity enhancement, and stability enhancement.

HER2-targeted, enzyme-activated liposomes show superior in vivo efficacy in an ovarian cancer model

Liposomes carrying chemotherapeutic drugs can accumulate passively in solid tumors at high levels. However, additional targeting of the liposomes towards e.g. receptors expressed on cancer cells may improve their interaction and therapeutic properties. In this study, we designed a liposomal delivery system, which utilizes the intrinsic characteristics of HER2-positive tumors to ensure efficient delivery of oxaliplatin to the cancer cells. On the liposome surface, trastuzumab, an antibody specific to the HER2 receptor, was shown to facilitate internalization by the cancer cells. A polyethylene glycol (PEG) layer on the liposome surface provides protection from mononuclear phagocyte system uptake. To optimize the interaction between liposomes and cancer cells, a protease-sensitive cleavable peptide linker was inserted at the base of each PEG. The PEG layer is then cleaved off by intra- and extracellular matrix metalloproteinases (MMPs) upon accumulation in the tumor. Our data demonstrate that the removal of PEG significantly destabilizes the liposomes and leads to substantial oxaliplatin release. The proposed beneficial effect of combining antibody-mediated internalization with MMP sensitivity was confirmed in a series of in vivo studies using ovarian cancer xenograft models. The results demonstrated that HER2-targeted MMP-sensitive liposomes have superior anticancer activity compared to non-targeted and non-cleavable liposomes.

Efficacy of a new system of targeted delivery of tenecteplase in acute myocardial infarction in an in vivo experiment

A new system of targeted delivery of tissue plasminogen activator tenecteplase for restoration of coronary blood flow in acute myocardial infarction in animal experiments was developed.The new system of targeted delivery of fibrinolytic consists of native (“free”) and encapsulated (“bound”) tenecteplase in liposomes, in the percentage ratio (60 and 40 %, respectively), which are conjugated through carboxylated dextran with fibrin-specific monoclonal antibodies Fnl-3C.The physicochemical characteristics of the obtained liposomes conjugated with fibrin-specific monoclonal antibodies (immunoliposomes) with tenecteplase were determined: immunoliposomes have a hydrodynamic diameter of ~76‒77 nm, a zeta potential of ~(‒33) mV, a polydispersity index of ~0.55. Modification of liposomes with fibrin-specific monoclonal antibodies does not alter thrombolytic activity.When using immunoliposomes the survival rate of animals with acute myocardial infarction is ~90 %, liposomal and native form of the drug ‒ 80 %.The use of immunoliposomal delivery system in animals with acute myocardial infarction leads to an increase in the free lumen of the infarct-related artery (p < 0.05) by 26 % compared to the liposomal delivery system and by 46 % compared to native tenecteplase. At the same time, the mass of ischemic myocardium on the background of thrombolytic therapy with>< 0.05) by 26 % compared to the liposomal delivery system and by 46 % compared to native tenecteplase. At the same time, the mass of ischemic myocardium on the background of thrombolytic therapy with immunoliposomes decreases (p < 0.05) by 16 % in rats in comparison with the liposomal system and by 26 % in comparison with native tenecteplase. The new system of targeted delivery of tenecteplase provides effective and safe thrombolysis in animal experiment> < 0.05) by 16 % in rats in comparison with the liposomal system and by 26 % in comparison with native tenecteplase.The new system of targeted delivery of tenecteplase provides effective and safe thrombolysis in animal experiment.

Tracking Drugs and Lipids: Quantitative Mass Spectrometry Imaging of Liposomal Doxorubicin Delivery and Bilayer Fate in Three-Dimensional Tumor Models.

Targeted therapy to the tumor would greatly advance precision medicine. Many drug delivery vehicles have emerged, but liposomes are cited as the most successful to date. Recent efforts to develop liposomal drug delivery systems focus on drug distribution in tissues and ignore liposomal fate. In this study, we developed a novel method to elucidate both drug and liposomal bilayer distribution in a three-dimensional cell culture model using quantitative matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI qMSI) alongside fluorescence microscopy. Imaging liposomal distribution in a cell culture model is challenging, as lipids forming the bilayer are endogenous to the model system. To resolve this issue, we functionalized the bilayer by chemically cross-linking a fluorescent tag to the alkyne-containing lipid hexynoyl phosphoethanolamine (HPE). We synthesized liposomes incorporating the tagged HPE lipid and encapsulated within them doxorubicin, yielding a theranostic liposome capable of both drug delivery and monitoring liposomal uptake. We employed an "in-tissue" MALDI qMSI approach to generate a calibration curve with R2 = 0.9687, allowing for quantification of doxorubicin within spheroid sections at multiple time points. After 72 h of treatment with the theranostic liposomes, full doxorubicin penetration was observed. The metabolites doxorubicinone and 7-deoxydoxorubicinone were also detected after 48 h. Modification of the bilayer allowed for fluorescence microscopy tracking of liposomes, while MALDI MSI simultaneously permitted the imaging of drugs and metabolites. While we demonstrated the utility of our method with doxorubicin, this system could be applied to examine the uptake, release, and metabolism of many other liposome-encapsulated drugs.

Nanotechnology-Based Strategy for Enhancing Therapeutic Efficacy in Pancreatic Cancer: Receptor-Targeted Drug Delivery by Somatostatin Analog

A novel nanotechnology-based drug delivery system (DDS) targeted at pancreatic cancer cells was developed, characterized, and tested. The system consisted of liposomes as carriers, an anticancer drug (paclitaxel) as a chemotherapeutic agent, and a modified synthetic somatostatin analog, 5-pentacarbonyl-octreotide, a ligand for somatostatin receptor 2 (SSTR2), as a targeting moiety for pancreatic cancer. The cellular internalization, cytotoxicity, and antitumor activity of the DDS were tested in vitro using human pancreatic ductal adenocarcinoma (PDAC) cells with different expressions of the targeted SSTR2 receptors, and in vivo on immunodeficient mice bearing human PDAC xenografts. The targeted drug delivery system containing paclitaxel exhibited significantly enhanced cytotoxicity compared to non-targeted DDS, and this efficacy was directly related to the levels of SSTR2 expression. It was found that octreotide-targeted DDS proved exceptionally effective in suppressing the growth of PDAC tumors. This study underscores the potential of octreotide-targeted liposomal delivery systems to enhance the therapeutic outcomes for PDAC compared with non-targeted liposomal DDS and Paclitaxel-Cremophor® EL, suggesting a promising avenue for future cancer therapy innovations.

AN UPDATED REVIEW OF STEALTH LIPOSOMES AND ITS ABILITY TO EVADE THE IMMUNE SYSTEM: A NEW FRONTIER IN CANCER CHEMOTHERAPY

Liposomes have been the delivery of choice for the cancer targeting therapy for the last few decades. Since the 1990s, the development of sterically stabilized (stealth) liposomes has garnered interest for their long circulating half-life. PEGylated (Polyethylene Glycol) liposomes are most extensively studied for delivering cancer therapeutics in a sustained manner. Stealth liposomes are having a less intrinsic toxicity with higher efficacy in cancer treatment. There are numerous clinical trials on the liposomes in tackling cancer is evident for the better outcome of the delivery system. Stealth liposomes are extensively studied for their improved circulation time and better pharmacokinetic profile in cancer treatment. The steric hindrance of the stealth liposomes bypasses the reticuloendothelial system clearance. Further the ligands conjugation in the surface of the liposomes able to achieve better target to the cancer cells. The vascularization nature of the cancerous cells is readily making the liposomal delivery of the cancer drugs accumulate in the cancerous cells rather than healthy cells. There is an utmost need to understand the possible mechanism of stealth liposomes and the basic science behind the development of liposomal delivery system in advancing the cancer treatment with less toxicity. The present review addresses the various modalities of the liposomal development, liposome characterization, mechanism of PEGylated liposomes, the advancements and results of the liposomes in the treatment of various diseases, and the clinical trials and regulatory considerations of liposomal drug delivery system.

Novel, engineered fusogenic liposome-based anti-oxidant delivery system improves the blood-brain barrier integrity in aging

Vascular dysfunction plays a pivotal role in age-related cognitive decline and neurodegeneration. The aging process often leads to a loss of integrity in the blood-brain barrier (BBB), initiating neuroinflammation and contributing to a decline in cognitive function. In previous research, we demonstrated the potential of resveratrol (RSV), a natural polyphenol, to target cerebromicrovascular endothelial cells (CMVECs), effectively countering age-related oxidative stress and improving vascular function, both in vitro and in vivo. However, the limited bioavailability of resveratrol raised questions about its effectiveness concerning the BBB and neuroinflammation. Our study aimed to address this challenge by introducing a novel drug delivery system designed to enhance the effciency of polyphenol delivery. This innovative approach involved the use of fusogenic liposomes (FL) integrated with a bioengineered protein corona (PC) featuring specific apolipoprotein E (ApoE). Our central hypothesis posited that PC formation could be harnessed to directly target CMVECs and enhance liposomal uptake, with the ultimate objective of effectively delivering RSV to the brain's microvessels in aging subjects (ApoE-FL-RSV). Our investigation encompassed the characterization of ApoE-FL uptake by CMVECs, along with an analysis of its biodistribution and pharmacokinetics in vivo. Remarkably, our findings revealed a significant increase in ApoE-FL-RSV accumulation within CMVECs in vivo, compared to control FL uptake. We employed advanced in vivo multiphoton imaging to longitudinally monitor the effects of ApoE-FL-RSV on the BBB, which demonstrated a significant rejuvenation of the endothelial barrier function in aged mice treated with ApoE-FL-RSV. In light of these results, we concluded that the fusogenic liposomal delivery system holds promise as a viable pharmacological intervention for addressing age-related vascular cognitive impairment. AHA834339, RF1AG072295, R01AG055395, R01AG068295; R01AG070915, K01AG073614, R01NS100782, R01CA255840, and Presbyterian Health Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Enzymatically Triggered Peptide-Lipid Conjugation of Designed Membrane Active Peptides for Controlled Liposomal Release.

Possibilities for controlling the release of pharmaceuticals from liposomal drug delivery systems can enhance their efficacy and reduce their side effects. Membrane-active peptides (MAPs) can be tailored to promote liposomal release when conjugated to lipid head groups using thiol-maleimide chemistry. However, the rapid oxidation of thiols hampers the optimization of such conjugation-dependent release strategies. Here, we demonstrate a de novo designed MAP modified with an enzyme-labile Cys-protection group (phenylacetamidomethyl (Phacm)) that prevents oxidation and facilitates in situ peptide lipidation. Before deprotection, the peptide lacks a defined secondary structure and does not interact with maleimide-functionalized vesicles. After deprotection of Cys using penicillin G acylase (PGA), the peptide adopts an α-helical conformation and triggers rapid release of vesicle content. Both the peptide and PGA concentrations significantly influence the conjugation process and, consequently, the release kinetics. At a PGA concentration of 5 μM the conjugation and release kinetics closely mirror those of fully reduced, unprotected peptides. We anticipate that these findings will enable further refinement of MAP conjugation and release processes, facilitating the development of sophisticated bioresponsive MAP-based liposomal drug delivery systems.

Rational design of a nonclassical liposomal nanoscale drug delivery system for innovative cancer therapy

AbstractAdvanced drug delivery systems are widely considered to be powerful approaches for treating cancer and many other diseases because of their superior ability to improve pharmacokinetics, promote lesion‐targeted delivery efficacy, and/or reduce the toxic effects of diverse therapeutics. Owing to the unique biomimetic structure of lipid bilayers surrounding aqueous cavities, liposomes have been found to encapsulate various therapeutics, ranging from small molecules with different hydrophobicities to biomacromolecules. With the advent of surface PEGylation, stealth liposomes with excellent in vivo long‐circulating behaviors have been generated, thus these liposomes have been extensively explored for the development of liposomal drugs with greatly improved in vivo pharmacokinetic behaviors by functioning as delivery vehicles. Inspired by their successes in clinical practice, stealth liposomes have recently been utilized as the main building scaffold or surface coating layers of other nanoparticulate formulations, which are coined as nonclassical liposomal nanoscale drug delivery systems (NDDSs) in this review, to enable the rational design of next‐generation liposomal nanomedicine. Therefore, after overviewing the latest progress in the development of conventional liposome‐based nanomedicine, we will introduce the development of these nonclassical liposomal NDDSs as well as their innovative cancer treatment strategies. We will subsequently provide a critical perspective on the future development of new cancer nanomedicines based on these rationally designed nonclassical liposomal NDDSs.

Bioprinting of a Liposomal Oxygen-Releasing Scaffold for Ovary Tissue Engineering.

This study addresses a critical challenge in bioprinting for regenerative medicine, specifically the issue of hypoxia compromising cell viability in engineered tissues. To overcome this hurdle, a novel approach using a microfluidic bioprinter is used to create a two-layer structure resembling the human ovary. This structure incorporates a liposomal oxygen-releasing system to enhance cell viability. The bioprinting technique enables the simultaneous extrusion of two distinct bioinks, namely, bioink A (comprising alginate 1% and 5 mg/mL PEGylated fibrinogen in a 20:1 molar ratio) and bioink B (containing alginate 0.5%). In addition, liposomal catalase and hydrogen peroxide (H2O2) are synthesized and incorporated into bioinks A and B, respectively. The liposomes are prepared using thin film hydration with a monodisperse size (140-160 nm) and high encapsulation efficiency. To assess construct functionality, isolated human ovarian cells are added to bioink A. The bioprinted constructs, with or without liposomal oxygen-releasing systems, are cultured under hypoxic and normoxic conditions for 3 days. Live/Dead assay results demonstrate that liposomal oxygen-releasing systems effectively preserve cell viability in hypoxic conditions, resembling viability under normoxic conditions without liposomes. PrestoBlue assay reveals significantly higher mitochondrial activity in constructs with liposomal oxygen delivery systems under both hypoxic and normoxic conditions. The evaluation of apoptosis status through annexin V immunostaining shows that liposomal oxygen-releasing scaffolds successfully protect cells from hypoxic stress, exhibiting a proportion of apoptotic cells similar to normoxic conditions. In contrast, constructs lacking liposomes in hypoxic conditions exhibit a higher incidence of cells in early-stage apoptosis. In conclusion, the study demonstrates the promising potential of bioprinted oxygen-releasing liposomal scaffolds to protect ovarian stromal cells in hypoxic environments. These innovative scaffolds not only offer protection but also recapitulate the mechanical differences between the medulla and the cortex in the normal ovary structure. This opens new avenues for advanced ovary tissue engineering and transplantation strategies.

Amphotericin B in the Era of New Antifungals: Where Will It Stand?

Amphotericin B (AmB) has long stood as a cornerstone in the treatment of invasive fungal infections (IFIs), especially among immunocompromised patients. However, the landscape of antifungal therapy is evolving. New antifungal agents, boasting novel mechanisms of action and better safety profiles, are entering the scene, presenting alternatives to AmB's traditional dominance. This shift, prompted by an increase in the incidence of IFIs, the growing demographic of immunocompromised individuals, and changing patterns of fungal resistance, underscores the continuous need for effective treatments. Despite these challenges, AmB's broad efficacy and low resistance rates maintain its essential status in antifungal therapy. Innovations in AmB formulations, such as lipid complexes and liposomal delivery systems, have significantly mitigated its notorious nephrotoxicity and infusion-related reactions, thereby enhancing its clinical utility. Moreover, AmB's efficacy in treating severe and rare fungal infections and its pivotal role as prophylaxis in high-risk settings highlight its value and ongoing relevance. This review examines AmB's standing amidst the ever-changing antifungal landscape, focusing on its enduring significance in current clinical practice and exploring its potential future therapeutic adaptations.

Abstract 5737: Enhancing cancer treatment Via a nanostructured chemoimmunotherapy gel facilitating interleukin-2 delivery and immunogenic cell death induction

Abstract Background: The landscape of immunotherapy, employing recombinant cytokines like interleukin-2 (IL-2), confronts challenges marked by its short half-life, systemic toxicity, and constrained tumor accumulation. These hurdles are particularly evident in the context of the immunosuppressive milieu characterizing pancreatic ductal adenocarcinoma (PDAC). Chemo-immuno-therapeutic synergies, notably those provoking immunogenic cell death (ICD), have demonstrated superior efficacy. This investigation delves into Pt-NHC as a type II ICD inducer to surmount immunosuppression and amplify antitumor immunity within a highly tumor-accumulated liposomal drug delivery system. Additionally, the co-administration of the angiotensin receptor blocker, losartan, mitigates desmoplasia in PDAC, further augmenting the efficacy of immunotherapy. Methods: To address the constraints of IL-2, a lipid-coated nanogel, IL2-Pt@Nanogel, was innovated, amalgamating silk fibroin-loaded IL-2 with Pt-NHC. The nanogel aimed to enhance IL-2 pharmacokinetics and optimize tumor targeting. Concurrently, losartan was employed to alleviate desmoplasia within the tumor microenvironment. Result: The chemoimmunotherapy nanogel, when coupled with losartan, showcased therapeutic potential in murine models of desmoplastic PDAC. Pt-NHC induced ER-localized reactive oxygen species (ROS) and DAMP release, reshaping the immunosuppressive microenvironment by repolarizing M2-type macrophages to M1 and diminishing the regulatory T-cell population. Co-delivery of IL-2 and Pt-NHC in the nanogel enhanced T-cell infiltration and activation, curbing tumor progression in primary and liver metastasized PDAC models. Importantly, the addition of losartan reduced collagen accumulation within tumors, resulting in heightened infiltration of effector T cells and more pronounced suppression of tumor growth in PDAC and metastasized liver. Conclusion: This study introduces an innovative nanogel delivery system (IL2-Pt@Nanogel) for chemoimmunotherapy, effectively addressing the challenges associated with IL-2 therapy. Leveraging the enhanced permeability and retention (EPR) effect, the nanogel improves IL-2 stability and tumor delivery. Pt-NHC incorporation induces ICD, reshaping the tumor microenvironment, and in synergy with losartan, elicits robust anticancer immunity. This strategy holds promise for clinical translation as a secure and efficient treatment for immunosuppressive and desmoplastic cancers, such as PDAC, presenting a distinctive therapeutic avenue. Citation Format: Hsuan Yu Mu, Yen-Nhi Ngoc Ta, Jing Rui Max Tham, Fu-Fei Hsu, Yu-Chieh Lin, Hsi-Chien Huang, Yun-Chieh Sung, Chih-I Huang, Ching-Ling Wu, Chao-Hung Chang, Sheng Yang, Tsung-Ying Lee, Jane Wang, Dan G. Duda, Yves Boucher, Jen-Huang Huang, Wee Han Ang, Yunching Chen. Enhancing cancer treatment Via a nanostructured chemoimmunotherapy gel facilitating interleukin-2 delivery and immunogenic cell death induction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5737.