Search Results (177)

Background/Objectives: PEGylated liposomes are widely recognized for their biocompatibility and capacity to extend systemic circulation via “stealth” properties. However, the PEG corona often limits tumor penetration and cellular internalization. Targeting matrix metalloproteinase-2 (MMP-2), frequently upregulated in breast cancer stroma, presents an opportunity to enhance tissue-specific drug delivery. In this study, we engineered MMP-2-responsive GPLGVRG peptide-modified cleavable PEGylated liposomes for targeted paclitaxel (PTX) delivery. Methods: Molecular docking simulations employed the MMP-2 crystal structure (PDB ID: 7XJO) to assess GPLGVRG peptide binding affinity. A cleavable, enzyme-sensitive peptide-PEG conjugate (Chol-PEG_2K-GPLGVRG-PEG_5K) was synthesized via small-molecule liquid-phase synthesis and characterized by ¹H NMR and MALDI-TOF MS. Liposomes incorporating this conjugate (S-Peps-PEG_5K) were formulated to evaluate whether MMP-2-mediated peptide degradation triggers detachment of long-chain PEG moieties, thereby enhancing internalization by 4T1 breast cancer cells. Additionally, the effects of tumor microenvironmental pH (~6.5) and MMP-2 concentration on drug release dynamics were investigated. Results: Molecular docking revealed robust GPLGVRG-MMP-2 interactions, yielding a binding energy of −7.1 kcal/mol. The peptide formed hydrogen bonds with MMP-2 residues Tyr A:23 and Arg A:53 (bond lengths: 2.4–2.5 Å) and engaged in hydrophobic contacts, confirming MMP-2 as the primary recognition site. Formulations containing 5 mol% Chol-PEG_2K-GPLGVRG-PEG_5K combined with 0.15 µg/mL MMP-2 (S-Peps-PEG_5K +MMP) exhibited superior internalization efficiency and significantly reduced clonogenic survival compared to controls. Notably, acidic pH (~6.5) induced MMP-2-mediated cleavage of the GPLGVRG peptide, accelerating S-Peps-PEG_5K dissociation and facilitating drug release. Conclusions: MMP-2-responsive, cleavable PEGylated liposomes markedly improve PTX accumulation and controlled release at tumor sites by dynamically modulating their stealth properties, offering a promising strategy to enhance chemotherapy efficacy in breast cancer. Full article

Liposomes represent a cornerstone of modern drug delivery systems due to their unique structural and physicochemical characteristics. Extensive research has refined their formulation, stability, and targeting capabilities, leading to numerous clinical applications, particularly in oncology. A key clinical feature is their ability to accumulate in malignant tissues via the enhanced permeability and retention effect, offering improved pharmacokinetics and reduced systemic toxicity. Advances in liposomal engineering, including PEGylation and ligand-based targeting, have significantly enhanced pharmacokinetic profiles and tissue specificity, minimizing off-target toxicity. The modern approach to nanocarrier-based drugs offers multidirectional perspectives on targeted therapy. Liposomes can bypass drug resistance mechanisms and provide controlled or stimuli-responsive drug release. Current trends in liposome research focus on hybrid nanocarriers, personalized medicine applications, and combination therapies. Full article

Neurodegenerative and neuroinflammatory diseases of the central nervous system are closely linked to aging and sustained oxidative and inflammatory stress. Polyphenols, plant-derived secondary metabolites, exhibit broad biological activities, including antioxidant and anti-inflammatory effects, the modulation of pathways such as PI3K/Akt, MAPK, Nrf2, and CREB, and the regulation of neurogenesis and microglial activation. This review focuses on the cell-specific actions of selected polyphenols in neurons, astrocytes, microglia, and oligodendrocytes within the context of Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. A major limitation to the therapeutic use of polyphenols is their poor bioavailability, due to instability, low solubility, and limited blood–brain barrier penetration. Liposomal nanocarriers are explored as promising delivery systems to overcome these barriers. Both conventional and functionalized liposomes (e.g., PEGylated, receptor-targeted) are discussed, alongside in vitro and in vivo studies demonstrating enhanced efficacy compared to free compounds. Intranasal delivery is also presented as a viable alternative to oral administration. Overall, polyphenols offer great potential as neuroprotective agents, and liposome-based delivery platforms have the potential to significantly enhance their clinical potential, provided that key formulation and targeting issues are addressed. Full article

A new method of the design of stimuli-sensitive multiliposomal containers for encapsulation and controlled drug release is described. Despite quite a wide choice of pH-sensitive containers, there is still a considerable challenge to synthesize those that respond quickly to small variations in pH and release most of the encapsulated drug in a short time. The suggested AMS-containing multiliposomal complexes demonstrated an excellent rate of encapsulated substance release under altering the pH of the outer solution. To improve the efficiency of the delivery of bioactive compounds to target cells and to increase the therapeutic effect, pH-sensitive liposomes were concentrated on the surface of the carrier- PEG-coated cationic liposomes. A pH-sensitive ampholytic derivative of cholan-24-oic acid embedded into the membrane of anionic liposomes allowed the rapid release of the cargo in the areas of low pH, such as tumors, inflammation sites, etc. The diameter of the complexes was optimized for passive targeting and typically ranged from 250 to 400 nm. The biodegradability of liposomes ensured enzymatic destruction of the multiliposomal containers and their elimination from the body after performing their transport function. The multiliposomal complexes and products of their biodegradation demonstrated low cytotoxicity. The composition of multiliposomal complexes, in particular, the amount of PEGylated lipid in the bilayer, was estimated to provide a high speed of the cargo release upon changing the pH. The novel developed pH-sensitive containers show potential for biomedical applications. Full article

Background/Objectives: While adenovirus (Ad) therapies have been proven to be effective in local administration, systemic Ad treatments have shown limited success due to pre-existing antibodies in the human blood that neutralize the virus. We developed a liposome coating procedure that protects the Ad from pre-existing neutralizing antibodies in human blood. To assess the in vivo stability of the liposomes, the present study used a novel in vivo method to quantitatively assess the protective capabilities of liposome-encapsulated Ad (DfAd) from neutralizing antibodies. Methods: The assay systemically administers DfAd with a green fluorescent protein transgene (DfAd-GFP) into pre-immunized mice and allows it to circulate in the presence of neutralizing antibodies; the infected blood is extracted and used to transduce HEK293 cells, which emits fluorescence in the presence of protected, un-neutralized Ad. Results: The PEGylated liposome formulation provides 12× protection in vivo relative to unencapsulated Ads. In vitro optimization of the liposome coating reveals a strong correlation between the structural stability of liposomes and protection against anti-Ad neutralizing antibodies, where DSPE-PEG2000-carboxylic acid (DSPE-PEG2000-CA) is a critical component for liposome stability and increasing protection against antibody neutralization of the encapsulated Ad. Conclusions: The findings in the present study confirm that the DfAd liposome can protect against neutralizing antibodies in blood circulation. The novel in vivo assay for liposome protection against neutralizing antibodies and in vitro experiments in the present study provide new tools and insights toward designing liposome–Ad complexes for the systemic treatment of cancer. Full article

The occurrence of antibiotic-resistant bacteria is a serious global health issue, and it emphasizes the need for novel antimicrobial agents. This review explores the potential of snake venom as another alternative strategy against antimicrobial resistance. Snake venoms are complex combinations of bioactive peptides and proteins, including metalloproteases (MPs), serine proteases (SPs), phospholipase A₂ (PLA₂) enzymes, three-finger toxins (3FTXs), cysteine-rich secretory proteins (CRISPs), L-amino acid oxidases (LAAOs), and antimicrobial peptides (AMPs). The antibacterial products possess wide-spectrum antibacterial activity against resistant microbes via diverse mechanisms such as cell membrane disruption, enzymatic hydrolysis of microbial structures, generation of oxidative stress, inhibition of biofilms, and immunomodulation. Strong antimicrobial activity is reported by most studies, but these are mostly restricted to in vitro testing with low translational use. Although preliminary insights into molecular targets and physiological effects exist, further studies are needed to clarify long-term safety and therapeutic potential. Special attention is given to snake venom-derived extracellular vesicles (SVEVs), which enhance the therapeutic potential of venom toxins by protecting them from degradation, improving bioavailability, and facilitating targeted delivery. Furthermore, innovative delivery strategies such as PEGylation, liposomes, hydrogels, microneedle patches, biopolymer films, and nanoparticles are discussed for their role in reducing systemic toxicity and enhancing antimicrobial efficacy. The rational modification of venom-derived peptides further expands their therapeutic utility by improving pharmacokinetics and minimizing off-target effects. Together, these approaches highlight the translational potential of snake venom-based therapies as next-generation antimicrobials in the fight against resistant infections. By outlining these challenges and directions, this review positions snake venom as an overlooked but fertile resource in the battle against antibiotic resistance. Full article

Background/Objectives: [6]-Gingerol ([6]-G), a bioactive compound derived from Zingiber officinale (ginger), exhibits strong anticancer potential but is hindered by poor aqueous solubility and low bioavailability. This study aimed to develop and evaluate PEGylated liposomal [6]-G (6-G-Lip) to enhance its stability, bioavailability, and chemopreventive efficacy in benzo[a]pyrene (BaP)-induced lung carcinogenesis. Methods: 6-G-Lip was synthesized using a modified thin-film hydration technique and characterized for size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE%), and release kinetics. The chemopreventive effects were assessed in BaP-induced lung cancer in Swiss albino mice, with prophylactic 6-G-Lip administration from two weeks before BaP exposure through 21 weeks. Cancer biomarkers, antioxidant enzyme activity, reactive oxygen species (ROS) generation, induction of apoptosis, and histopathological alterations were analyzed. Results: 6-G-Lip exhibited a particle size of 129.7 nm, a polydispersity index (PDI) of 0.16, a zeta potential of −18.2 mV, and an encapsulation efficiency (EE%) of 91%, ensuring stability and effective drug loading. The formulation exhibited a controlled release profile, with 26.5% and 47.5% of [6]-G released in PBS and serum, respectively, at 72 h. 6-G-Lip significantly lowered cancer biomarkers, restored antioxidant defenses (SOD: 5.60 U/min/mg protein; CAT: 166.66 μm H₂O₂/min/mg protein), reduced lipid peroxidation (MDA: 3.3 nm/min/mg protein), and induced apoptosis (42.2%), highlighting its chemopreventive efficacy. Conclusions: This study is the first to prepare, characterize, and evaluate PEGylated [6]-G-Lip for the chemoprevention of lung cancer. It modulates oxidative stress, restores biochemical homeostasis, and selectively induces apoptosis. These findings support 6-G-Lip as a promising nanotherapeutic strategy for cancer prevention. Full article

Doxorubicin (DOX), an anthracycline chemotherapeutic agent, demonstrates efficacy against various types of cancer. Combining DOX with the antihypertensive drug hydralazine (HDZ) has been proposed as cardioprotective combination therapy, allowing for the use of a reduced DOX dose. The current study describes the remote co-loading of DOX and HDZ into PEGylated liposomes using, for the first time, a simultaneous pH gradient technique. First, PEGylated liposomes were prepared using an ethanol injection method and remotely loaded with DOX and HDZ. Then, DOX- and HDZ-loaded liposomes (Lip-DOX-HDZ) were characterized using DLS, TEM, FTIR, thermal analysis, drug leakage, and stability. Furthermore, the cellular uptake and cytotoxicity were evaluated in two human breast cancer cell lines (MCF7 and MDA-MB-231) and two normal cell lines (human dermal fibroblasts (HDFs) and rat cardiac cells (H9C2)). The results revealed that Lip-DOX-HDZ had a particle size of 158 ± 18 nm, PDI of 0.22 ± 0.08, and zeta potential of −22 ± 5 mV. The encapsulation efficiency of DOX and HDZ was 90% and 30%, respectively. Moreover, the IC₅₀ values of Lip-DOX-HDZ showed higher cytotoxicity against the MDA-MB-231 (5.5 ± 0.4 µM) and MCF7 (6.25 ± 0.9 µM) breast cancer cell lines compared to normal cells: HDF cells (20 ± 3.0 µM) and H9C2 cardiac cells (19.37 ± 2.0 µM). Our study found that remotely loaded Lip-DOX-HDZ showed a ~4-fold lower toxicity and selectivity for normal cells (HDFs and H9C2), compared to breast cancer cells. This suggests that Lip-DOX-HDZ is a promising nanocarrier for both DOX and HDZ, clinically potent molecules. Full article

Precision medicine aims to tailor treatments to individual patients based on their unique characteristics and disease pathophysiology. This study presents a novel mathematical model of breast tumor growth, specifically focusing on implanted breast tumors in mice treated with Pegylated Liposomal Doxorubicin (PLD). The model describes drug pharmacokinetics, drug resistance development, and the evolution of tumor mass over time. The introduction of a compartment for drug resistance development represents the novel aspect of this work, providing a straightforward description of this critical process. The model was adapted to observed data on two mice and model parameters were estimated. To assess the qualitative properties of the model solutions and to investigate its potential limitations, a stability analysis was conducted to identify equilibrium points. The analysis revealed that if the tumor cell spontaneous elimination rate exceeds the growth rate, then the tumor is stable, preventing any form of treatment. On the contrary, the pathological case occurs, the equilibrium becomes unstable, and the tumor requires treatment. By accurately modeling drug pharmacokinetics and resistance development, this model can inform clinical decisions by predicting patient-specific responses to PLD treatment, thereby guiding personalized therapeutic strategies. The findings from this study contribute to a deeper understanding of tumor growth dynamics and provide valuable insights for the development of personalized treatment strategies. Full article

Background: Steric stabilization of liposomes using PEGylation has been used widely in pharmaceutical research to overcome the limitations of conventional liposomes and to extend circulation time. PEGylation tended to improve the physicochemical stability and reverse the chemoresistance in multidrug-resistant (MDR) breast cancer cell lines. In this study, PEGylated formulations of disulfiram (DS) and paclitaxel (PAC) were developed using the ethanol-based proliposome technology. Methods: PEGylated liposomal formulations of disulfiram (DS) and paclitaxel (PAC) were developed using the ethanol-based proliposome approach combined with high-pressure homogenization (HPH). The liposomes were characterized for particle size, polydispersity index (PDI), zeta potential, drug loading efficiency (DLE%), and drug entrapment efficiency (DEE%). Cytotoxicity studies were performed on sensitive (MCF7, MDA-MB-231) and chemoresistant (MDA-MB-231_PAC10) breast cancer cell lines using the MTT assay to assess the anti-ancer potential of the formulations. Synergistic cytotoxic effects of DS and PAC co-delivery were also evaluated. Results: There was no significant difference in drug loading (DLE%) and drug entrapment efficiency (EE%) between conventional liposomes and the developed PEGylated vesicles. DS demonstrated higher loading in liposomes than PAC, and a greater cytotoxic effect on both sensitive (MCF7 and MDA-MB-231) and chemoresistant (MDA-MB-231_PAC10) human breast cancer cell lines. For both DS- and PAC-loaded liposomes, PEGylation did not compromise the cytotoxic effect on both sensitive and chemoresistant cells. Interestingly, the combination of DS- and PAC-loaded PEGylated liposomes had significantly higher cytotoxic effect and lower IC50 than that of each drug alone. Conclusions: Overall, PEGylated liposomal formulation of DS and PAC acted synergistically to reverse the multidrug resistance in breast cancer cells and could serve as a promising system for delivery of PAC and DS simultaneously in one formulation using an alcohol-based proliposome formulation. Full article

Background: Preclinical studies on liposomal interleukin (IL) therapy demonstrate considerable promise in cancer treatment. This review explores the achievements, challenges, and future potential of liposomal IL encapsulation, focusing on preclinical studies. Methods: A structured search was conducted using the PubMed and Web of Science databases with the following search terms and Boolean operators: (“liposomal interleukin” OR “liposome-encapsulated interleukin”) AND (“gene therapy” OR “gene delivery”) AND (“cancer” OR “tumor” OR “oncology”) AND (“pre-clinical studies” OR “animal models” OR “in vitro studies”. Results: Liposomal IL-2 formulations are notable for enhancing delivery and retention at tumor sites. Recombinant human interleukin (rhIL-2) adsorbed onto small liposomes (35–50 nm) substantially reduces metastases in murine models. Hepatic metastasis models demonstrate superior efficacy of liposomal IL-2 over free IL-2 by enhancing immune responses, particularly in the liver. Localized delivery strategies, including nebulized liposomal IL-2 in canine pulmonary metastases and intrathoracic administration in murine sarcoma models, reduce systemic toxicity while promoting immune activation and tumor regression. Liposomal IL gene therapy, delivering cytokine genes directly to tumor sites, represents a notable advancement. Combining IL-2 gene therapy with other cytokines, including IL-6 or double-stranded RNA adjuvants, synergistically enhances macrophage and T-cell activation. Liposomal IL-4, IL-6, and IL-21 therapies show potential across various tumor types. Pairing liposomal IL-2 with chemotherapy or immune agents improves remission and survival. Innovative strategies, including PEGylation and ligand-targeted systems, optimize delivery, release, and therapeutic outcomes. Conclusions: Utilizing immune-stimulatory ILs through advanced liposomal delivery and gene therapy establishes a strong foundation for advancing cancer immunotherapy. Full article

Background/Objectives: Epilepsy is one of the most common chronic neurological disorders, characterized by alterations in neuronal electrical activity that result in recurrent seizures and involuntary body movements. Anticonvulsants are the primary treatment for this condition, helping patients improve their quality of life. However, the development of new drugs with fewer side effects and greater economic accessibility remains a key focus in nanomedicine. Macamides, secondary metabolites derived from Maca (Lepidium meyenii), represent a promising class of novel drugs with diverse therapeutic applications, particularly in the treatment of neurological disorders. Methods: In this study, we optimized the potential of the macamide N-3-methoxybenzyl-linoleamide (3-MBL) as an anticonvulsant agent through its encapsulation in PEGylated liposomes conjugated with OX26 F(ab′)₂ fragments. Results: These immunoliposomes exhibited a size of 120.52 ± 9.46 nm and a zeta potential of −8.57 ± 0.80 mV. Furthermore, in vivo tests using a pilocarpine-induced status epilepticus model revealed that the immunoliposomes provided greater efficacy against epileptic seizures compared to the free form of N-3-methoxybenzyl-linoleamide at the same dose. Notably, the observed anticonvulsant effect was comparable to that of carbamazepine, a traditional FDA-approved antiepileptic drug. Conclusions: This pioneering work employs liposomal nanocarriers to deliver macamides to the brain, aiming to set a new standard for the use of modified liposomes in anticonvulsant epilepsy treatment. Full article

Throughout the last 5 years, extensive research has been carried out towards the development of effective treatments for coronavirus disease 2019 (COVID-19). Regardless of the worldwide efforts, only a few drugs have passed clinical trials, and there is still a need to develop therapies, especially for those who are particularly vulnerable to a severe disease course. Maleimide-functionalized liposomes are proposed to serve as a platform for the immobilization, stabilization, and delivery of a short peptide sequence with high affinity towards severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, extensive optimizations should be performed in order to achieve features required for a reliable drug candidate, such as homogeneity of physical parameters and their long-term stability. Here, we present a step-by-step development process for maleimide-functionalized liposomes, which—once decorated with the SARS-CoV-2-binding peptide—could inhibit the infection progress of COVID-19. The main emphasis is placed on defining optimal lipid composition and formation conditions of PEGylated liposomes. We propose that the developed nanocarrier technology can be used as a universal platform for the construction of multiple antiviral agents. Full article

Background/Objectives: Ovarian cancer is the fifth most common cancer among women, with an estimated 19,680 new cases projected in 2024. Adjuvant chemotherapy remains the standard treatment for epithelial ovarian cancers but is frequently associated with adverse events, such as chemotherapy-induced alopecia (CIA). CIA is a particularly distressing side effect that significantly affects the body image, self-esteem, and quality of life of patients. Unfortunately, CIA remains underexplored in patients with ovarian cancer. Methods: This scoping review analyzed PubMed- and EMBASE-indexed studies investigating the incidence, severity, and mechanisms of CIA in ovarian cancer patients. Eighteen studies were included for analysis. Results: Our analysis identified platinum-based compounds, taxanes, and topoisomerase I inhibitors as the agents most strongly correlated with severe alopecia, particularly in combination regimens such as carboplatin–paclitaxel (CP), and cyclophosphamide, adriamycin, and cisplatin (CAP). Among the monotherapies, taxanes, including paclitaxel and docetaxel, posed the highest risk of CIA. Mild-to-moderate alopecia was observed in patients treated with gemcitabine or pegylated liposomal doxorubicin. Alternative factors such as dosing schedules and prior chemotherapy exposure also significantly influence CIA severity. Conclusions: Given the profound psychosocial impact of CIA, optimizing treatment protocols to reduce the severity of alopecia without compromising therapeutic efficacy is crucial. These findings offer insights that may guide future therapeutic strategies for improving patient outcomes and quality of life. Full article

Background: Retrospective studies are often criticized for their susceptibility to case selection bias compared to prospective studies, which include all patients consecutively and are thus less prone to such limitations. However, the larger sample sizes typical of retrospective studies can sometimes offset this drawback. On behalf of the Fondazione Italiana Linfomi (FIL), a substantial retrospective study involving 946 patients was conducted to examine the use of non-pegylated liposomal anthracycline (Myocet). This was followed by a prospective study, the Prospective Elderly Project, which enrolled 308 patients treated with the same liposomal anthracycline regimen. Methods: The objective of this analysis was to determine whether the patient cohort from the retrospective study significantly differed from the cohort in the prospective study. Statistical hypothesis testing was applied to assess whether the samples from both studies originated from the same underlying population. The Anderson–Darling test, a non-parametric statistical method, was utilized to evaluate and compare the overall survival distributions between the two patient cohorts. Results: The statistical tests produced conflicting results, suggesting a potential selection bias in the retrospective study or the possibility that the two groups were from the same population. These discrepancies may have arisen due to the choice of statistical methods or the quality of the data analyzed. Conclusions: This study highlights the challenges of comparing retrospective and prospective cohorts and underscores the importance of selecting appropriate statistical methodologies. The findings provide valuable insights and lay the groundwork for developing innovative approaches to improve such comparisons in future research. Full article