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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.

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., (© 2024. The Author(s).)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Liposomes were one of the earliest drug delivery vehicles used for anti-cancer therapeutics and similarly, lipid-based nanoparticles have been used for abundance of applications as gene therapies. The methods to produce these particles have remained relatively unchanged until the recent emergence of continuous manufacturing. Continuous processing enables accelerated development of nanoparticle formulations while providing a scalable manufacturing solution. For this work a continuous processing platform for the production of lipid and polymeric-based nanoparticle formulations has been developed at the University of Connecticut. This research focuses on the formation of liposomes encompassing multiple design of experiments (DoEs) to identify functional relationships between critical process parameters (CPPs), critical material attributes (CMAs), and critical quality attributes (CQAs) for liposomal formulations produced using this continuous processing platform. Liposomes of various sizes and of low polydispersity index (PDI) were produced with different material attributes under various processing conditions. In general, lower mole percentages of cholesterol produced larger particles whereas the mole percent of phosphatidylglycerol did not seem to have a s impact on the size of the liposomes that were produced. The results showed that similarly sized liposomes could be produced with different processing conditions allowing for the flexibility to operate in regions most suitable for formulation components that may be sensitive to certain processing conditions. For example, if the target size of a formulation is 100 nm but the active pharmaceutical ingredient is sensitive to temperature, then the formulation can be manufactured at high (55 °C) or low (30 °C) depending on its characteristics. Additionally, the relationships between CMAs and CPPs were different from conventional liposomal manufacturing methods, allowing for more flexibility when using a continuous processing system. Models that can effectively predict the hydrodynamic diameter of monodispersed liposomes produced using continuous processing were developed. The models developed from the DoEs in this study may be useful for accelerated development of new lipid formulations as well as facilitate the translation from traditional manufacturing methods to continuous manufacturing for products already on the market., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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), 3β-[ 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., Competing Interests: The authors report no conflicts of interest in this work.

A study of the formulation of liposomal preparations of riboflavin (RF) with compositional variations in the content of phosphatidylcholine (PC) and their entrapment efficiency (26-42%) have been conducted. Light transmission characteristics of the liposomal preparations have been determined to evaluate their effect on the amount of light passing through the system to initiate a photochemical reaction. Dynamic light scattering (DLS) and atomic force microscopy (AFM) have been used to study the physical characteristics of liposomes. The liposomal preparations of RF have been subjected to photolysis using visible light and the apparent first- order rate constant, kobs, for the degradation of RF have been determined. The values of kobs (1.73-2.29×10(-3)min(-1)) have been found to decrease linearly with an increase in PC concentration in the range of 12.15 to 14.85 mM. Thus, an increase in PC concentration of liposomes leads to an increase in the stability of RF. RF and its main photoproduct, lumichrome (LC), formed in liposomes have been assayed by a two-component spectrometric method at 356 and 445 nm using an irrelevant absorption correction to compensate for the interference of liposomal components. The fluorescence measurements of RF in liposomes indicate excited singlet state quenching and the formation of a charge-transfer complex between RF and PC. It results in electron transfer from PC to RF to cause photoreduction and stabilization of RF., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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]

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]

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]

• Due to the lack of an effective vaccine and pentavalent antimony resistance in Bihar, amphotericin b (AmB) has become the first-line treatment for VL. • Currently, the drug is available in many forms. Either "conventionally" complexed with sodium deoxycholate (ABD), as a cholesteryl sulfate complex (ABCD), as a lipid complex (ABLC), and as a liposomal formulation (LAMB). • We are on the verge of kala-azar elimination today because of amphotericin b. • Moreover, the use of amphotericin b helps patients with Kala-Azar to prevent relapses. Visceral leishmaniasis or Kala-azar is a vector-borne disease caused by an intracellular parasite of the genus leishmania. In India, Amphotericin B (AmB) is a first-line medication for treating leishmaniasis. After a large-scale resistance to pentavalent antimony therapy developed in Bihar state, it was rediscovered as an effective treatment for Leishmania donovani infection. AmB which binds to the ergosterol of protozoan cells causes a change in membrane integrity resulting in ions leakage, and ultimately leading to cell death. The treatment effect of liposomal AmB can be seen more quickly than deoxycholate AmB because, it has some toxic effects, but liposomal AmB is significantly less toxic. Evidence from studies suggested that ABLC (Abelcet) and ABCD (Amphotec) are as effective as l -AmB but Liposomal form (Ambisome) is a more widely accepted treatment option than conventional ones. Nevertheless, the world needs some way more efficient antileishmanial drugs that are less toxic and less expensive for people living with parasitic infections caused by Leishmania. So, academics, researchers, and sponsors need to focus on finding such drugs. This review provides a summary of the chemical, pharmacokinetic, drug-target interactions, stability, dose efficacy, and many other characteristics of the AmB and their various formulations. We have also highlighted the clinically significant aspects of PKDL and VL co-infection with HIV/TB. [ABSTRACT FROM AUTHOR]

Topical DNA vaccines have been shown to elicit both broad humoral and cellular immune responses in vivo. The skin is an attractive site for the delivery of DNA antigens for DNA vaccination. However, due to skin's barrier properties, the penetration of DNA and the applications of topical vaccination are limited. To improve permeability, chemical and physical approaches have been examined to decrease stratum corneum barrier properties. Topical vaccination has been achieved using topical application of naked DNA, DNA/liposomes or emulsion complex, liposomal cream, as well as physical methods such as stripping, electroporation, and micromechanical disruption methods. All methods resulted in a significant enhancement in humoral and cellular immune responses over naked DNA alone. To develop more cost-effective and needle-free vaccines, skin-targeted immunizations are required. This review focuses on the chemical and physical methods developed to enhance DNA delivery into skin. [ABSTRACT FROM AUTHOR]

Summary. We report a case of life-threatening nasal sinus zygomycosis that developed during remission induction therapy for a relapsed acute lymphoblastic leukaemia. The patient was successfully treated with liposomal amphotericin B and granulocyte-colony stimulating factor followed by surgical reconstruction of the resultant cutaneous defect. [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. [ABSTRACT FROM AUTHOR]