Liposomal Drug Research Articles

Liposomal Drug Delivery: Comparative Kinetics, Efficacy, and Applications in Targeted Therapeutics

During the Second World War, in order to reduce infections in soldiers wounds, nurses had to inject the injured with multiple shots of penicillin per day because one single shot of penicillin only lasts a short period of time, but the lack of human resources prevented some of the wounded soldiers from receiving the dose of penicillin that they needed[1]. To reduce the need for human labor in penicillin intake, Romansky discovered that mixing penicillin with lipids would prolong the time in which penicillin has effect. This innovation saved a lot of people from infection at the time. Lipid-based drug carriers have been developed and innovated even more throughout the years.A few years ago, the COVID-19 pandemic has facilitated advancements in vaccination technologies, including the use authorization of mRNA vaccines encapsulated in lipid nanoparticles. Traditional drug delivery methods, such as oral intake, injection, and transdermal applications, usually face challenges like low accuracy, toxicity, and variable effectiveness. However, liposomes, discovered in the 1960s, emerged as a drug carrier that, due to their specific structure, allowed for prolonged and site-specific drug release. Liposomes can encapsulate drugs of different molecular qualities, allowing lipid-based drug carriers to have excellent performance in carrying both hydrophobic and hydrophilic drugs. This paper examines the composition of liposomes, the different factors of the lipid bilayers, and the release kinetics in drug delivery. Using a hybrid modeling approach of first-order kinetics and the Higuchi model, the study simulates drug release profiles. The liposomal formulation of drugs demonstrates the potential of lipid-based delivery systems in enhancing the efficacy while minimizing side effects of treatments.

Research progress of liposome drug delivery system in the treatment of head and neck cancer

Head and neck tumors are one of the major diseases that threaten human health. Targeted chemotherapy is an important treatment for head and neck tumors. However, many anti-cancer drugs are difficult to reach effective concentrations in tumors and can cause damage to normal tissues. Therefore, the efficient delivery of anti-tumor drugs, improvement of their therapeutic effects, and reduction of their adverse effects on the whole body and locally are urgent issues in targeted drug research. Liposomes have been widely studied due to their unique characteristics, including amphiphilicity, biocompatibility, biodegradability, and low toxicity. This article outlines the current applications and prospects of liposome drug delivery systems in different treatment modalities for head and neck tumors in recent years, aiming to provide more options for the treatment of head and neck tumors.

Self-assembling PEGylated mannolipids for liposomal drug encapsulation of natural products

The chemical synthesis of modified neoglycolipids is reported in an effort to further improve the drug delivery properties of previously described mannosylated liposomes possessing alkyl linkers in the aglyconic moiety.

Interaction of Liposomes Containing the Carrageenan/Echinochrome Complex with Human HaCaT Keratinocytes In Vitro.

Liposomal drug delivery systems are successfully used in various fields of medicine for external and systemic applications. Marine organisms contain biologically active substances that have a unique structure and exhibit a wide range of biological activities. Polysaccharide of red seaweed (carrageenan (CRG)), and water-insoluble sea urchin pigment (echinochrome (Ech)) interact with each other and form a stable complex. We included the CRG/Ech complex in liposomes for better permeability into cells. In our research, tetramethylrhodamine isothiocyanate TRITC-labeled CRG was synthesized to study the interaction of the complex encapsulated in liposomes with human epidermal keratinocytes (HaCaTs) widely used to expose the skin to a variety of substances. Using confocal microscopy, we found that liposomes were able to penetrate HaCaT cells with maximum efficiency within 24 h, and pre-incubation of keratinocytes with liposomes resulted in the delivery of the CRG/Ech complex into the cytoplasm. We investigated the anti-inflammatory effects of liposomes, including the lysosomal regulation, increased intracellular ROS levels, and increased NO synthesis in lipopolysaccharide (LPS)- or Escherichia coli (E. coli)-induced inflamed skin cells. Liposomes containing the CRG/Ech complex significantly reduced lysosomal activity by 26% in LPS-treated keratinocytes and decreased ROS levels in cells by 23% after LPS exposure. It was found that liposomes with the complex improved the migration of HaCaT keratinocytes incubated with high-dose LPS by 47%. The results of the work, taking into account the good permeability of liposomes into keratinocytes, as well as the anti-inflammatory effect on cells treated with LPS or E. coli, show the prospects of using liposomes containing the CRG/Ech complex as an anti-inflammatory agent in the fight against skin infections.

Abstract A020: Liposomal topotecan with low-intensity focused ultrasound utilization to improve drug penetration with brain parenchyma in pediatric brain tumors

Abstract The blood-brain barrier (BBB) remains a significant obstacle in delivering effective chemotherapeutics to treat pediatric brain tumors, limiting drug penetration and reducing therapeutic outcomes. To overcome this challenge, we investigated the use of liposomal topotecan (TPT), encapsulated in a sonosensitive formulation, designed for controlled release triggered by low-intensity focused ultrasound (LIFU). In this study, we evaluated the in vitro efficacy of a sonosensitive liposomal topotecan formulation. The liposomal topotecan was created using remote loading with an ammonium sulfate gradient. TPT was loaded at a drug-to-lipid ratio of 1:10. The liposome was composed of hydrogenated soy PC, cholesterol, and DSPE-PEG2000. IC50 assay comparing free topotecan to the liposomal topotecan indicated that the cytoxicity of free TPT is lower than liposomal TPT indicating a sustained release of drug which would decrease long term toxicity. In addition, pharmcokinetic fluorescent quantification of liposomal topotecan showed linear increase in free drug (ug/uL) as liposomal TPT concentration is increased in brain homogenates. We hypothesize that tumor growth inhibition and overall survival would be significantly improved in mice receiving LIFU-mediated liposomal topotecan delivery. Our future work includes additional pharmokinetics with survival analysis in vivo with and without low intensity focused ultrasound. These results highlight the potential of combining liposomal drug formulations with focused ultrasound to overcome the challenges of BBB permeability, offering a promising therapeutic strategy for improving drug accumulation and survival outcomes in pediatric brain tumor models. Citation Format: Avani Mangoli, Sarah Kim, Kathryn Blethen, Angela Everhart, Sasha Nikiforov, Gerry Grant, Luke Avigliano. Liposomal topotecan with low-intensity focused ultrasound utilization to improve drug penetration with brain parenchyma in pediatric brain tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A020.

Cyclodextrin Drugs in Liposomes: Preparation and Application of Anticancer Drug Carriers.

Cyclodextrin complexes have been widely used in pharmaceutical applications, but disadvantages such as the rapid clearance of cyclodextrins from the blood stream after in vivo administration or their replacement by other molecules in the biological medium with higher luminal affinity for cyclodextrins limit the application of cyclodextrins as drug carriers. Liposome-encapsulated hydrophobic drugs have low and unstable drug loading rates. Drug-in-CD-in-liposome (DCL), which encapsulate cyclodextrin inclusion complexes into liposomes, combine the advantages of both delivery systems, can effectively avoid the leakage and rapid release of lipophilic drugs in the lipid bilayer, and help to maintain the integrity of liposomes. This paper focuses on the preparation method, characterization and application of DCL, with a view to providing methods and references for the research and application of DCL technology.

Therapeutic mechanisms of glucocorticoids, their administration and chronotherapy

Glucocorticoids represent a cornerstone in the treatment of inflammatory and autoimmune diseases due to their potent anti-inflammatory and immunosuppressive effects. These steroid hormones, including endogenous cortisol and synthetic analogs like prednisone and dexamethasone, exert their effects through genomic and non-genomic pathways, targeting key inflammatory mediators. While genomic mechanisms regulate long-term gene expression, non-genomic pathways enable rapid modulation of immune responses, particularly at high doses. Despite their therapeutic efficacy, glucocorticoid use is often limited by significant adverse effects, including osteoporosis and metabolic disorders. Chronotherapy, which aligns medication timing with circadian rhythms, enhances therapeutic outcomes while reducing side effects, particularly in diseases like rheumatoid arthritis where inflammation peaks in the early morning. Emerging innovations, such as selective glucocorticoid receptor agonists (SEGRAs) and liposomal drug delivery systems, offer targeted anti-inflammatory effects with reduced systemic toxicity. These advancements highlight the potential for optimizing glucocorticoid therapy to achieve maximum efficacy while mitigating adverse effects. This review underscores the importance of understanding glucocorticoid mechanisms, administration methods, and novel therapeutic strategies to improve outcomes in inflammatory and autoimmune diseases.

Improving dexamethasone drug loading and efficacy in treating rheumatoid arthritis via liposome: Focusing on inflammation and molecular mechanisms.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 0.46% of the global population. Conventional therapeutics for RA, including disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, frequently result in unintended adverse effects. Dexamethasone (DEX) is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties. Liposomal delivery of DEX, particularly when liposomes are surface-modified with targeting ligands like peptides or sialic acid, can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity. This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA. Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models, reduces joint inflammation and damage, and alleviates cartilage destruction compared to free DEX. The liposomal formulation also shows better hemocompatibility, fewer adverse effects on body weight and immune organ index, and a longer circulation time with higher bioavailability. The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) and B-cell-activating factor (BAFF), which are key players in the pathogenesis of RA. Additionally, liposomal DEX can induce the expression of anti-inflammatory cytokines like interleukin-10 (IL-10), which has significant anti-inflammatory and immunoregulatory properties. The findings suggest that liposomal DEX represents a promising candidate for effective and safe RA therapy, with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.

Liposomal Drug Delivery System for the Management of Prostate Cancer: An Update

Abstract: Prostate cancer is a significant health concern affecting a large population of males worldwide. Liposomes, with their versatile properties and drug delivery capabilities, hold promise as a targeted and efficient delivery system for prostate cancer treatment. Various studies have explored different liposomal formulations loaded with anticancer agents to improve drug efficacy, reduce side effects, and enhance targeted delivery to prostate cancer cells. Future research in this area should focus on refining liposomal formulations to maximize drug encapsulation, stability, and specific targeting of prostate cancer cells. Understanding the tumor microenvironment and utilizing stimuli-responsive liposomes can further enhance drug release at the targeted site. Additionally, investigating the biodistribution and pharmacokinetics of liposomal drug delivery systems in vivo will provide valuable insights into their efficacy and potential for clinical translation. Overall, liposome-based drug delivery systems have the potential to revolutionize prostate cancer treatment, ultimately improving patient outcomes and quality of life. Further advancements and continued research in this field will contribute to the development of effective and personalized therapeutic strategies for prostate cancer patients.

Construction of Sorafenib Tosylate and Etoposide‐loaded Liposomes: A Path to Precision Liver Cancer Therapy and its Apoptosis Induction

AbstractNanotechnology is an effective tool in fighting against cancer, playing a crucial role in investigating and fabricating novel anticancer drugs. Recognizing the worldwide prevalence of cancer, we combined sorafenib tosylate (ST) and etoposide (ETP) within liposomes. We assessed their ability to kill human umbilical vein endothelial cells (HUVECs) and HepG2 liver cancer cells. The liposomes effectively contained ST and ETP, exhibiting a particle size distribution below 180 nm, a polydisperse index (PDI) below 0.2, a spherical shape, a strong negatively charged zeta potential, and encapsulation efficiencies of 59% for ST, 88% for ETP, and 57% for ST combined with 87% for ETP. The FTIR analysis indicates that the drugs were incorporated within liposomes. Encapsulation of the drugs in liposomes resulted in a more significant cytotoxic impact on HepG2 cells and a reduced cytotoxic impact on HUVECs. The morphological assessment of the HepG2 liver cancer cells was investigated using AO‐EB and Hoechst 33258 staining methods. Apoptosis mechanisms of HepG2 cells were examined by Annexin V and PI dual staining. Furthermore, the coadministration of ST and ETP, which were enclosed in liposomes, resulted in a synergistic impact on the drugs, leading to cell death by apoptosis.

Iontophoresis-driven alterations in nanoparticle uptake pathway and intracellular trafficking in carcinoma skin cancer cells.

Effective treatment of squamous cell carcinoma (SCC) poses challenges due to intrinsic drug resistance and limited drug penetration into tumor cells. Nanoparticle-based drug delivery systems have emerged as a promising approach to enhance therapeutic efficacy; however, they often face hurdles such as inadequate cellular uptake and rapid lysosomal degradation. This study explores the potential of iontophoresis to augment the efficacy of liposome and immunoliposome-based drug delivery systems for SCC treatment. The study assessed iontophoresis effects on SCC cell line (A431) viability, nanoparticle uptake dynamics, and intracellular distribution patterns. Specific inhibitors were employed to delineate cellular internalization pathways, while fluorescence microscopy and immunohistochemistry examined changes in EGFR expression and lysosomal activity. Results demonstrated that iontophoresis significantly increased cellular uptake of liposomes and immunoliposomes, achieving approximately 50 % uptake compared to 10 % with passive treatment. This enhancement correlated with modifications in endocytic pathways, favoring macropinocytosis and caveolin-mediated endocytosis for liposomes, and macropinocytosis and clathrin-mediated pathways for immunoliposomes. Moreover, iontophoresis induced alterations in EGFR distribution and triggered syncytium-like cellular clustering. It also attenuated lysosomal activity, thereby reducing nanoparticle degradation and prolonging intracellular retention of therapeutic agents. These findings underscore the role of iontophoresis in modulating nanoparticle internalization pathways, offering insights that could advance targeted drug delivery strategies and mitigate therapeutic resistance in SCC and other malignancies.

Fabrication of Biomimetic Hybrid Liposomes via Microfluidic Technology: Homotypic Targeting and Antitumor Efficacy Studies in Glioma Cells.

The treatment of glioblastoma is hindered by the blood-brain barrier (BBB) and rapid drug clearance by the immune system. To address these challenges, we propose a novel drug delivery system using liposomes modified with cell membrane fragments. These modified liposomes can evade the immune system, cross the BBB, and accumulate in tumor tissue through homotypic targeting, thereby delivering drugs like paclitaxel and carboplatin more effectively. In this work, the hybrid liposomes were synthesized using microfluidics and integrating 3D printing to produce the microfluidic devices. In vitro, we explored the homotypic targeting capability, BBB passing ability, and therapeutic efficacy of paclitaxel and carboplatin. The production of hybrid liposomes by microfluidics has been key to creating high-quality biomimetic nanoparticles, and the integration of 3D printing has simplified the production of microfluidic devices, making the process more efficient and economical. In vitro experiments have shown that these drug-loaded biomimetic hybrid liposomes are able to reach the homotypic target, cross the BBB, and maintain the efficacy of paclitaxel and carboplatin. The development of biomimetic hybrid liposomes represents a promising approach for the treatment of glioblastoma. By combining the advantages of liposomal drug delivery with the stealth properties and targeting capabilities of cell membrane fragments, these nanoparticles can potentially overcome the challenges associated with traditional therapies.

A Narrative Review on Clinical and Experimental Evidence of Shatavari Ghrut

Ayurvedic dosage forms possess unique characteristics in both formulation and therapeutic applications. Sneha Kalpana encompasses a range of medicated oils and ghee-based products, which are effectively used to treat a diverse array of ailments across various age demographics. On the other hand, the liposomal drug delivery system represents a modern advancement in traditional medicine. Shatavari Ghrut (SG) is a notable formulation that falls under the category of Ghrut Kalpana in Ayurveda. There are numerous references to SG in Ayurvedic classics for various diseases. It is fascinating to observe the wide range of applications and the growing interest in the efficacy of SG through clinical and preclinical studies. Narrative reviews play a crucial role in summarising existing evidence and identifying gaps in knowledge for further exploration. Here’s an outline of the potential therapeutic uses and the importance of narrative reviews in evaluating SG. Relevant sources include Ayurvedic texts and scientific databases such as Pubmed, Scopus, Ayush Research Portal, ResearchGate, Digital Helpline for Ayurveda Research Articles (DHARA), Cochrane, Shodhganga, and Google Scholar, using keywords like Asparagus racemosus Wild, clinical studies on Shatavari Ghrut, lipid preparations of Shatavari, preclinical studies on Shatavari Ghrut, and Shatavari as a key.

Unified synthesis of DSPC and PSPC: Chemical entities of hydrogenated soy L-α-phosphatidylcholine (HSPC), a key component of liposomal drug formulations

Unified synthesis of DSPC and PSPC: Chemical entities of hydrogenated soy L-α-phosphatidylcholine (HSPC), a key component of liposomal drug formulations

Liposomal Codelivery of Doxorubicin and Curcumin Sensitizes Antitumor Activity and Reduces Tumor Metastasis.

Multidrug resistance (MDR) is a major obstacle to traditional cancer treatment using chemotherapeutic agents like doxorubicin (DOX). MDR affects drug dosage regimens and enables the recurrence and metastasis of cancer. Because DOX causes severe side effects at high dosages, it is important to use an MDR modulator to make cancer cells sensitive to DOX. This work focused on a liposome-based codelivery system containing curcumin (CUR) and DOX, focusing on CUR as an MDR modulator. The synergistic effect was maximized when the ratio of DOX and CUR was 1:1, and the synthesis of liposomal drugs was successfully verified. In addition, a successful MDR reversal effect was demonstrated through rhodamine 123 assay, Western blotting, and immunofluorescence. Compared to the conventional DOX treatment, the dual-drug treatment exhibits a significantly improved anticancer effect. In the murine metastasis 4T1 IP tumor model, the dual-drug-encapsulating liposomes successfully suppressed tumor growth and reversed the tumoral effect (omental tumor metastasis, fat, and muscle weight loss) into a normal state.

Nanoliposomes Meet Folic Acid: A Precision Delivery System for Bleomycin in Cancer Treatment

Overview: The targeted administration of anticancer therapies, particularly through folate receptor (FR)-mediated targeting, enhances treatment effectiveness while minimizing side effects. This study assesses the therapeutic potential of folate-targeted liposomal bleomycin (FL-BLM) against traditional forms in treating human ovarian carcinoma and oral cancer. Methods: FL-BLM was created using the thin film hydration technique with folic acid integration for active targeting. Its efficacy was compared to non-targeted liposomal bleomycin (L-BLM) and traditional bleomycin (BLM) using the MTT assay and flow cytometry to measure G2/M phase cell cycle arrest. Results: FL-BLM demonstrated significantly greater effectiveness in reducing cell viability and inducing G2/M phase arrest in oral cancer cells (HN cells, OECM-1) and ovarian cancer cells (A2780CP) compared to L-BLM and BLM, indicating successful folate-mediated targeting. Conclusions: FL-BLM effectively targets and inhibits FR-overexpressing cancer cells, particularly in both cancers. This supports the potential of folate-mediated targeting in liposomal drug delivery systems for improving drug delivery and reducing toxicity. Future research should further explore FR-targeted therapies across various cancer types

Liposomal topical drug administration surpasses alternative methods in glaucoma therapeutics: a novel paradigm for enhanced treatment.

Glaucoma is a leading cause of permanent blindness. Despite therapeutic advancements, glaucoma management remains challenging due to limitations of conventional drug delivery, primarily topical eye drops, resulting in suboptimal outcomes and a global surge in cases. To address these issues, liposomal drug delivery has emerged as a promising approach. This review explores the potential of liposomal-based medications, with a particular focus on topical administration as a superior alternative to enhance therapeutic efficacy and improve patient compliance compared to existing treatments. This writing delves into the therapeutic prospects of liposomal formulations across different administration routes, as evidenced by ongoing clinical trials. Additionally, critical aspects of liposomal production and market strategies are discussed herein. By overcoming ocular barriers and optimizing drug delivery, liposomal topical administration holds the key to significantly improving glaucoma treatment outcomes.

Rg3-lipo biomimetic delivery of paclitaxel enhances targeting of tumors and myeloid-derived suppressor cells.

Liposomal drug delivery systems have revolutionized traditional cytotoxic drugs. However, the relative instability and toxicity of the existing liposomal drug delivery systems compromised their efficacy. Herein, we present Rg3-lipo, an innovative drug delivery system using a glycosyl moiety-enriched ginsenoside (Rg3). This system is distinguished by its glycosyl moieties exposed on the liposomal surface. These moieties imitate human cell membranes to stabilize and evade phagocytic clearance. The Rg3-lipo system loaded with paclitaxel (PTX-Rg3-lipo) demonstrated favorable bioavailability and safety in Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys. With its glycosyl moieties recognizing tumor cells via the glucose transporter Glut1, PTX-Rg3-lipo inhibited gastric, breast, and esophageal cancers in human cancer cell lines, tumor-bearing mice, and patient-derived xenograft models. These glycosyl moieties selectively targeted myeloid-derived suppressor cells (MDSCs) through the glucose transporter Glut3 to attenuate their immunosuppressive effect. The mechanism study revealed that Rg3-lipo suppressed glycolysis and downregulated the transcription factors c-Maf and Mafb overcoming the MDSC-mediated immunosuppressive microenvironment and enhancing PTX-Rg3-lipo's antitumor effect. Taken together, we supply substantial evidence for its advantageous bioavailability and safety in multiple animal models, including nonhuman primates, and Rg3-lipo's dual targeting of cancer cells and MDSCs. Further investigation regarding Rg3-lipo's druggability will be conducted in clinical trials.

Leveraging machine learning to streamline the development of liposomal drug delivery systems

Drug delivery systems efficiently and safely administer therapeutic agents to specific body sites. Liposomes, spherical vesicles made of phospholipid bilayers, have become a powerful tool in this field, especially with the rise of microfluidic manufacturing during the COVID-19 pandemic. Despite its efficiency, microfluidic liposomal production poses challenges, often requiring laborious, optimization on a case-by-case basis. This is due to a lack of comprehensive understanding and robust methodologies, compounded by limited data on microfluidic production with varying lipids. Artificial intelligence offers promise in predicting lipid behaviour during microfluidic production, with the still unexploited potential of streamlining development. Herein we employ machine learning to predict critical quality attributes and process parameters for microfluidic-based liposome production. Validated models predict liposome formation, size, and production parameters, significantly advancing our understanding of lipid behaviour. Extensive model analysis enhanced interpretability and investigated underlying mechanisms, supporting the transition to microfluidic production. Unlocking the potential of machine learning in drug development can accelerate pharmaceutical innovation, making drug delivery systems more adaptable and accessible.

Targeted Therapy of Antibody-Induced Autoimmune Arthritis Using Peptide-Guided Nanoparticles.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and it affects over 18 million people worldwide. Despite the availability of a variety of potent drugs for RA, over 30-40 percent of patients fail to achieve adequate remission, and many patients suffer from systemic adverse effects. Thus, there is an urgent need for a joint-targeted drug delivery system. Nanotechnology-based drug delivery methods offer a promising resource that is largely untapped for RA. Using the T cell-driven rat adjuvant-induced arthritis (AA) model of human RA, we developed a peptide-targeted liposomal drug delivery system for arthritis therapy. It was based on a novel joint-homing peptide ART-2 to guide liposomes entrapping dexamethasone (Dex) to arthritic joints of rats, and this approach was more effective in suppressing arthritis than the unpackaged (free) drug. To de-risk the translation of our innovative drug delivery technology to RA patients, we undertook the validation of ART-2-liposomal delivery in a genetically and mechanistically distinct arthritis model in mice, the collagen antibody-induced arthritis (CAIA) model. Using live imaging for tissue distribution of liposomes in vivo, immunohistochemistry of paws for cellular binding of ART-2, and liposomal Dex delivery, our results fully validated the key findings of the rat model, namely, preferential homing of peptide-functionalized liposomes to arthritic joints compared to healthy joints, and higher efficacy of liposomal Dex than free Dex. These results offer a proof-of-concept for the benefits of targeted drug delivery to the joints and its potential translation to RA patients.