Capturing sources of health system legitimacy in fragmented conflict zones under different governance models: a case study of northwest Syria.

INTRODUCTION: Legitimacy and trust are crucial for resilient health systems in fragmented conflict zones. This study evaluates the legitimacy of health systems in northwest Syria under different governance models. METHODS: Using a deductive and inductive mixed-methods approach, the research team developed a framework with an index, 4 sub-indices and 18 indicators to assess the legitimacy of health systems using different governance models - top-down, bottom-up, and hybrid - in the context of the response to the earthquake that hit Syria in February 2023. The study includes surveys, workshops, stakeholder consultations, and an expert panel conducted in northwest Syria and online. RESULTS: The findings indicate that bottom-up health governance model is perceived as the most legitimate, followed by the mixed model, while top-down model is perceived as the least legitimate. This preference is measured across all legitimacy source sub-indices, including legality, justification, consent and performance and across the overall Health System Legitimacy Index (HSLI). However, the hybrid governance approach showed limited superiority at two indicator levels regarding long-term health system response. CONCLUSION: This study highlights the importance of considering the legitimacy of the health system in fragmented conflict zones. It helps explain the effectiveness of the bottom-up approach and community-based governance in enhancing trust, cooperative behaviour, health interventions and achieving sustainability. Additionally, the study highlighted the role of legitimate health systems in practising civic virtue and promoting social justice, thus contributing to peace-building efforts. These insights are crucial for policymakers and development donors to strengthen health systems in challenging contexts.

An analysis of humanitarian and health aid harmonisation over a decade (2011-2019) of the Syrian conflict.

INTRODUCTION: Aid harmonisation is a key component of donor efforts to make aid more effective by improving coordination and simplifying and sharing information to avoid duplication. This study evaluates the harmonisation of health and humanitarian aid in Syria during acute humanitarian and health crises from 2011 to 2019. METHODS: Data on humanitarian and health aid for Syria between 2011 and 2019 was collected from the Organisation for Economic Cooperation and Development's Creditor Reporting System to assess the harmonisation of aid. The data was linked to four key indicators of the conflict: the number of internally displaced persons; the number of people in need of humanitarian assistance; the number or frequency of internal movements (displacements) by individuals; and the decline in Syria's population between 2011 and 2019. This was compared with data from highly fragile states and developing countries. Four focus group discussions, four key informants' interviews and three consultations with humanitarian practitioners were also conducted. RESULTS: The findings suggest that overall aid harmonisation did not occur and importantly did not correlate with increased humanitarian needs. During the first 5 years, humanitarian and health pooled funds (which endorse aid harmonisation) in Syria were nearly entirely absent, far less than those in developing countries and highly fragile states. However, from 2016 to 2019, a visible surge in humanitarian pooled funds indicated an increase in the harmonisation of donors' efforts largely influenced by adopting the Whole of Syria approach in 2015 as a positive result of the cross-border United Nation (UN) Security Council resolution in 2014. CONCLUSION: Harmonisation of aid within the Syrian crisis was found to have little correlation with the crisis parameters and population needs, instead aligning more with donor policies. Assessing fragmentation solely at the donor level is also insufficient. Aid effectiveness should be assessed with the inclusion of community engagement and aid beneficiary perspectives. Harmonisation mechanisms must be disentangled from international politics to improve aid effectiveness. In Syria, this study calls for finding and supporting alternative humanitarian coordination and funding mechanisms that are not dependent on the persistent limitations of the UN Security Council.

"Enhancing Oral Drug Absorption: Overcoming Physiological and Pharmaceutical Barriers for Improved Bioavailability".

The oral route stands out as the most commonly used method for drug administration, prized for its non-invasive nature, patient compliance, and easy administration. Several elements influence the absorption of oral medications, including their solubility, permeability across mucosal membranes, and stability within the gastrointestinal (GI) environment. Research has delved into comprehending physicochemical, biochemical, metabolic, and biological obstacles that impact the bioavailability of a drug. To improve oral drug absorption, several pharmaceutical technologies and delivery methods have been studied, including cyclodextrins, micelles, nanocarriers, and lipid-based carriers. This review examines both traditional and innovative drug delivery methods, as well as the physiological and pharmacological barriers influencing medication bioavailability when taken orally. Additionally, it describes the challenges and advancements in developing formulations suitable for oral use.

Vaccination governance in protracted conflict settings: the case of northwest Syria.

BACKGROUND: Effective vaccination governance in conflict-affected regions poses unique challenges. This study evaluates the governance of vaccination programs in northwest Syria, focusing on effectiveness, efficiency, inclusiveness, data availability, vision, transparency, accountability, and sustainability. METHODS: Using a mixed-methods approach, and adapting Siddiqi's framework for health governance, data were collected through 14 key informant interviews (KIIs), a validating workshop, and ethnographic observations. Findings were triangulated to provide a comprehensive understanding of vaccination governance. RESULTS: The study highlights innovative approaches used to navigate the complex health governance landscape to deliver vaccination interventions, which strengthened sub-national vaccination structures such as The Syria Immunisation Group (SIG). The analysis revealed several key themes. Effectiveness and efficiency were demonstrated through cold-chain reliability and extensive outreach activities, though formal reports lacked detailed analysis of vaccine losses and linkage between disease outbreak data and coverage statistics. Key informants and workshop participants rated the vaccination strategy positively but identified inefficiencies due to irregular funding and bureaucracy. Inclusiveness and data availability were prioritised, with outreach activities targeting vulnerable groups. However, significant gaps in demographic data and reliance on paper-based systems hindered comprehensive coverage analysis. Digitalisation efforts were noted but require further support. The SIG demonstrated a clear strategic vision supported by international organizations such as the World Health Organization, yet limited partner participation in strategic planning raised concerns about broader ownership and engagement. While the SIG was perceived as approachable, the lack of public documentation and financial disclosure limited transparency. Internal information sharing was prevalent, but public communication strategies were insufficient. Accountability and sustainability faced challenges due to a decentralized structure and reliance on diverse donors. Despite stabilizing factors such as decentralization and financial continuity, fragmented oversight and reliance on donor funding remained significant concerns. DISCUSSION: The study highlights the complexities of vaccination governance in conflict-affected areas. Comparisons with other conflict zones underscore the importance of local organisations and international support. The SIG's role is pivotal, but its legitimacy, transparency, and inclusivity require improvement. The potential transition to early recovery in Syria poses additional challenges to SIG's sustainability and integration into national programs. CONCLUSION: The governance of vaccination in northwest Syria is multifaceted, involving multiple stakeholders and lacking a legitimate government. Enhancing transparency, local ownership, and participatory decision-making are crucial for improving governance. The role of international bodies is essential, emphasising the need for structured feedback mechanisms and transparent monitoring processes to ensure the program's success and sustainability.

Infection prevention and control in conflict-affected areas in northeast Syria: A cross-sectional study.

Objectives: In northeastern Syria (NES), the adherence of health care facilities to infection prevention and control (IPC) standards remains underexplored. This study evaluates the IPC performance of various health facilities against World Health Organization (WHO) benchmarks using the IPC Assessment Framework (IPCAF) and the Hand Hygiene Self-Assessment Framework (HHSAF). Methods: We conducted a cross-sectional survey of 33 health care facilities, including primary (PHC), secondary (SHC), and tertiary health care centres (THC). Data were collected via on-site evaluations using the IPCAF and HHSAF tools. Results: A significant 91% of facilities did not meet half of the WHO IPC minimum requirements. Specifically, 57% of PHCs met 26-50% of the standards, while none exceeded 75%. Among SHCs, 71% met 26-50% of the standards, while 44% of THCs fell within this range. Notably, 81.8% of facilities were classified as 'inadequate' per the IPCAF, with none achieving 'intermediate' or 'advanced' levels. The HHSAF results were similarly concerning, with 34.4% deemed 'inadequate' and 65.6% at the 'basic' level. A weak positive correlation (0.137) was found between IPCAF and HHSAF scores. Conclusions: NES health care facilities demonstrate substantial deficiencies in IPC compliance, with critical gaps in IPC programmes, health care-associated infection surveillance, and training. Urgent interventions are required to enhance IPC practices, leveraging local strengths and fostering international collaborations to improve patient safety and health care quality in the region.

Caspase inhibitors: a review on recently patented compounds (2016-2023).

INTRODUCTION: Caspases are a family of protease enzymes that play a crucial role in apoptosis. Dysregulation of caspase activity has been implicated in various pathological conditions, making caspases an important focus of research in understanding cell death mechanisms and developing therapeutic strategies for diseases associated with abnormal apoptosis. AREAS COVERED: It is a comprehensive review of caspase inhibitors that have been comprising recently granted patents from 2016 to 2023. It includes peptide and non-peptide caspase inhibitors with their application for different diseases. EXPERT OPINION: This review categorizes and analyses recently patented caspase inhibitors on various diseases. Diseases linked to caspase dysregulation, including neurodegenerative disorders, and autoimmune conditions, are highlighted to accentuate the therapeutic relevance of the patented caspase inhibitors. This paper serves as a valuable resource for researchers, clinicians, and pharmaceutical developers seeking an up-to-date understanding of recently patented caspase inhibitors. The integration of recent patented compounds, structural insights, and mechanistic details provides a holistic view of the progress in caspase inhibitor research and its potential impact on addressing various diseases.

Expanding the Role of Chiral Drugs and Chiral Nanomaterials as a Potential Therapeutic Tool.

Chirality, the property of molecules having mirror-image forms, plays a crucial role in pharmaceutical and biomedical research. This review highlights its growing importance, emphasizing how chiral drugs and nanomaterials impact drug effectiveness, safety, and diagnostics. Chiral molecules serve as precise diagnostic tools, aiding in accurate disease detection through unique biomolecule interactions. The article extensively covers chiral drug applications in treating cardiovascular diseases, CNS disorders, local anesthesia, anti-inflammatories, antimicrobials, and anticancer drugs. Additionally, it explores the emerging field of chiral nanomaterials, highlighting their suitability for biomedical applications in diagnostics and therapeutics, enhancing medical treatments.

Cell-penetrating peptides for sustainable agriculture.

Cell-penetrating peptides (CPPs) are short (typically 5-30 amino acids), cationic, amphipathic, or hydrophobic peptides that facilitate the cellular uptake of diverse cargo molecules by eukaryotic cells via direct translocation or endocytosis across the plasma membrane. CPPs can deliver a variety of bioactive cargos, including proteins, peptides, nucleic acids, and small molecules into the cell. Once inside, the delivered cargo may function in the cytosol, nucleus, or other subcellular compartments. Numerous CPPs have been used for studies and drug delivery in mammalian systems. Although CPPs have many potential uses in plant research and agriculture, the application of CPPs in plants remains limited. Here we review the structures and mechanisms of CPPs and highlight their potential applications for sustainable agriculture.

A comprehensive review on doxorubicin: mechanisms, toxicity, clinical trials, combination therapies and nanoformulations in breast cancer.

Doxorubicin is a key treatment for breast cancer, but its effectiveness often comes with significant side effects. Its actions include DNA intercalation, topoisomerase II inhibition, and reactive oxygen species generation, leading to DNA damage and cell death. However, it can also cause heart problems and low blood cell counts. Current trials aim to improve doxorubicin therapy by adjusting doses, using different administration methods, and combining it with targeted treatments or immunotherapy. Nanoformulations show promise in enhancing doxorubicin's effectiveness by improving drug delivery, reducing side effects, and overcoming drug resistance. This review summarizes recent progress and difficulties in using doxorubicin for breast cancer, highlighting its mechanisms, side effects, ongoing trials, and the potential impact of nanoformulations. Understanding these different aspects is crucial in optimizing doxorubicin's use and improving outcomes for breast cancer patients. This review examines the toxicity of doxorubicin, a drug used in breast cancer treatment, and discusses strategies to mitigate adverse effects, such as cardioprotective agents and liposomal formulations. It also discusses clinical trials evaluating doxorubicin-based regimens, the evolving landscape of combination therapies, and the potential of nanoformulations to optimize delivery and reduce systemic toxicity. The review also discusses the potential of liposomes, nanoparticles, and polymeric micelles to enhance drug accumulation within tumor tissues while sparing healthy organs.

Recent advancements and applications of ophthalmic gene therapy strategies: A breakthrough in ocular therapeutics.

Over the past twenty years, ocular gene therapy has primarily focused on addressing diseases linked to various genetic factors. The eye is an ideal candidate for gene therapy due to its unique characteristics, such as easy accessibility and the ability to target both corneal and retinal conditions, including retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), age-related macular degeneration (AMD), and Stargardt disease. Currently, literature documents 33 clinical trials in this field, with the most promising results emerging from trials focused on LCA. These successes have catalyzed further research into other ocular conditions such as glaucoma, AMD, RP, and choroideremia. The effectiveness of gene therapy relies on the efficient delivery of genetic material to specific cells, ensuring sustained and optimal gene expression over time. Viral vectors have been widely used for this purpose, although concerns about potential risks such as immune reactions and genetic mutations have led to the development of non-viral vector systems. Preliminary laboratory research and clinical investigations have shown a connection between vector dosage and the intensity of immune response and inflammation in the eye. The method of administration significantly influences these reactions, with subretinal delivery resulting in a milder humoral response compared to the intravitreal route. This review discusses various ophthalmic diseases, including both corneal and retinal conditions, and their underlying mechanisms, highlighting recent advances and applications in ocular gene therapies.

Health information management systems and practices in conflict-affected settings: the case of northwest Syria.

BACKGROUND: In conflict settings, as it is the case in Syria, it is crucial to enhance health information management to facilitate an effective and sustainable approach to strengthening health systems in such contexts. In this study, we aim to provide a baseline understanding of the present state of health information management in Northwest Syria (NWS) to better plan for strengthening the health information system of the area that is transitioning to an early-recovery stage. METHODS: A combination of questionnaires and subsequent interviews was used for data collection. Purposive sampling was used to select twenty-one respondents directly involved in managing and directing different domains of health information in the NWS who worked with local NGOs, INGOs, UN-agencies, or part of the Health Working Group. A scoring system for each public health domain was constructed based on the number and quality of the available datasets for these domains, which were established by Checci and others. RESULTS & CONCLUSIONS: Reliable and aggregate health information in the NWS is limited, despite some improvements made over the past decade. The conflict restricted and challenged efforts to establish a concentrated and harmonized HIS in the NWS, which led to a lack of leadership, poor coordination, and duplication of key activities. Although the UN established the EWARN and HeRAMS as common data collection systems in the NWS, they are directed toward advocacy and managed by external experts with little participation or access from local stakeholders to these datasets. RECOMMENDATIONS: There is a need for participatory approaches and the empowerment of local actors and local NGOs, cooperation between local and international stakeholders to increase access to data, and a central domain for planning, organization, and harmonizing the process. To enhance the humanitarian health response in Syria and other crisis areas, it is imperative to invest in data collection and utilisation, mHealth and eHealth technologies, capacity building, and robust technical and autonomous leadership.

Demographics and risk factors for suicide in Syria: A retrospective media content analysis of online news sources.

Since the beginning of the Syrian conflict in 2011, Syrians have faced violence and displacement causing an increase in mental health issues. The COVID-19 pandemic, the 2023 earthquake, and deteriorating living conditions have exacerbated these issues. Suicide in Syria remains an under-researched topic since accurate data are difficult to obtain. In this study, we aimed to explore the demographics and risk factors of suicide in Syria by performing a retrospective content analysis of selected online news (media) outlets from across Syria. Twelve news outlets from the three regions of Syria were selected and news of suicide cases were searched retrospectively. The age range was between 9 and 79 years old with the average age being 27.1 ± SD 5.9 years. The most reported causes of suicide were harsh living conditions (18.5%) and relationship problems (18.3%). The most common method of suicide was hanging followed by using firearms. More suicides occurred at night and in the summer and spring seasons. Based on our study's results, young adult, male, unmarried, individuals in rural settings and northern governorates were at the highest risk of suicide in Syria. This study highlights the urgent need for mental health interventions that address the unique challenges faced by Syrians.

A New Insight Into The Huisgen Reaction: Heterogeneous Copper Catalyzed Azide-Alkyne Cycloaddition for the Synthesis of 1,4-Disubstituted Triazole (From 2018-2023).

The Huisgen cycloaddition, often referred to as 1,3-Dipolar cycloaddition, is a well-established method for synthesizing 1,4-disubstituted triazoles. Originally conducted under thermal conditions [3+2] cycloaddition reactions were limited by temperature, prolonged reaction time, and regioselectivity. The introduction of copper catalyzed azide-alkyne cycloaddition (CuAAC) revitalized interest, giving rise to the concept of "click chemistry". The CuAAC has emerged as a prominent method for producing 1,2,3-triazole with excellent yields and exceptional regioselectivity even in unfavorable conditions. Copper catalysts conventionally facilitate azide-alkyne cycloadditions, but challenges include instability and recycling issues. In recent years, there has been a growing demand for heterogeneous and porous catalysts in various chemical reactions. Chemists have been more interested in heterogenous catalysts as a result of the difficulties in separating homogenous catalysts from reaction products. These catalysts are favored for their abundant active sites, extensive surface area, easy separation from reaction mixtures, and the ability to be reused. Heterogeneous catalysts have garnered significant attention due to their broad industrial utility, characterized by cost-effectiveness, stability, resistance to thermal degradation, and ease of removal compared to their homogeneous counterparts. The present review covers recent advancements from year 2018 to 2023 in the field of click reactions for obtaining 1,2,3-triazoles through Cu catalyzed 1,3-dipolar azide-alkyne cycloaddition and the properties of the catalyst, reaction conditions such as solvent, temperature, reaction time, and the impact of different heterogeneous copper catalysts on product yield.

Aptamer as a targeted approach towards treatment of breast cancer.

Aptamers, a novel type of targeted ligand used in drug delivery, have quickly gained popularity due to their high target specificity and affinity. Different aptamer-mediated drug delivery systems, such as aptamer-drug conjugate (ApDC), aptamer-siRNA, and aptamer-functionalised nanoparticle systems, are currently being developed for the successful treatment of cancer based on the excellent properties of aptamers. These systems can decrease potential toxicity and enhance therapeutic efficacy by targeting the drug moiety. In this review, we provide an overview of recent developments in aptamer-mediated delivery systems for cancer therapy, specifically for breast cancer, and talk about the potential applications and current issues of novel aptamer-based techniques. This study in aptamer technology for breast cancer therapy highlights key aptamers targeting well-established biomarkers such as HER2, oestrogen receptor, and progesterone receptor. Additionally, we explore the potential of aptamers in overcoming various challenges such as drug resistance and improving the delivery of therapeutic agents. This review aims to provide a deeper understanding of the present aptamer-based targeted delivery applications through in-depth analysis to increase efficacy and create new therapeutic approaches that may ultimately lead to better treatment outcomes for cancer patients.

Alternatives of Animal Models for Biomedical Research: a Comprehensive Review of Modern Approaches.

Biomedical research has long relied on animal models to unravel the intricacies of human physiology and pathology. However, concerns surrounding ethics, expenses, and inherent species differences have catalyzed the exploration of alternative avenues. The contemporary alternatives to traditional animal models in biomedical research delve into three main categories of alternative approaches: in vitro models, in vertebrate models, and in silico models. This unique approach to artificial intelligence and machine learning has been a keen interest to be used in different biomedical research. The main goal of this review is to serve as a guide to researchers seeking novel avenues for their investigations and underscores the importance of considering alternative models in the pursuit of scientific knowledge and medical breakthroughs, including showcasing the broad spectrum of modern approaches that are revolutionizing biomedical research and leading the way toward a more ethical, efficient, and innovative future. Models can insight into cellular processes, developmental biology, drug interaction, assessing toxicology, and understanding molecular mechanisms.

An Expedition on Synthetic Methodology of FDA-approved Anticancer Drugs (2018-2021).

New drugs being established in the market every year produce specified structures for selective biological targeting. With medicinal insights into molecular recognition, these begot molecules open new rooms for designing potential new drug molecules. In this review, we report the compilation and analysis of a total of 56 drugs including 33 organic small molecules (Mobocertinib, Infigratinib, Sotorasib, Trilaciclib, Umbralisib, Tepotinib, Relugolix, Pralsetinib, Decitabine, Ripretinib, Selpercatinib, Capmatinib, Pemigatinib, Tucatinib, Selumetinib, Tazemetostat, Avapritinib, Zanubrutinib, Entrectinib, Pexidartinib, Darolutamide, Selinexor, Alpelisib, Erdafitinib, Gilteritinib, Larotrectinib, Glasdegib, Lorlatinib, Talazoparib, Dacomitinib, Duvelisib, Ivosidenib, Apalutamide), 6 metal complexes (Edotreotide Gallium Ga-68, fluoroestradiol F-18, Cu 64 dotatate, Gallium 68 PSMA-11, Piflufolastat F-18, 177Lu (lutetium)), 16 macromolecules as monoclonal antibody conjugates (Brentuximabvedotin, Amivantamab-vmjw, Loncastuximabtesirine, Dostarlimab, Margetuximab, Naxitamab, Belantamabmafodotin, Tafasitamab, Inebilizumab, SacituzumabGovitecan, Isatuximab, Trastuzumab, Enfortumabvedotin, Polatuzumab, Cemiplimab, Mogamulizumab) and 1 peptide enzyme (Erwiniachrysanthemi-derived asparaginase) approved by the U.S. FDA between 2018 to 2021. These drugs act as anticancer agents against various cancer types, especially non-small cell lung, lymphoma, breast, prostate, multiple myeloma, neuroendocrine tumor, cervical, bladder, cholangiocarcinoma, myeloid leukemia, gastrointestinal, neuroblastoma, thyroid, epithelioid and cutaneous squamous cell carcinoma. The review comprises the key structural features, approval times, target selectivity, mechanisms of action, therapeutic indication, formulations, and possible synthetic approaches of these approved drugs. These crucial details will benefit the scientific community for futuristic new developments in this arena.

NOTCH Signaling Pathway: Occurrence, Mechanism, and NOTCH-Directed Therapy for the Management of Cancer.

It is now well understood that many signaling pathways are vital in carrying out and controlling essential pro-survival and pro-growth cellular functions. The NOTCH signaling pathway, a highly conserved evolutionary signaling pathway, has been thoroughly studied since the discovery of NOTCH phenotypes about 100 years ago in Drosophila melanogaster. Abnormal NOTCH signaling has been linked to the pathophysiology of several diseases, notably cancer. In tumorigenesis, NOTCH plays the role of a "double-edged sword," that is, it may act as an oncogene or as a tumor suppressor gene depending on the nature of the context. However, its involvement in several cancers and inhibition of the same provides targeted therapy for the management of cancer. The use of gamma (γ)-secretase inhibitors and monoclonal antibodies for cancer treatment involved NOTCH receptors inhibition, leading to the possibility of a targeted approach for cancer treatment. Likewise, several natural compounds, including curcumin, resveratrol, diallyl sulfide, and genistein, also play a dynamic role in the management of cancer by inhibition of NOTCH receptors. This review outlines the functions and structure of NOTCH receptors and their associated ligands with the mechanism of the signaling pathway. In addition, it also emphasizes the role of NOTCH-targeted nanomedicine in various cancer treatment strategies.

Hydroxamic acid derivatives as selective HDAC3 inhibitors: computer-aided drug design strategies.

Histone deacetylases (HDACs) are critical epigenetic drug targets that have gained significant attention in the scientific community for the treatment of cancer. The currently marketed HDAC inhibitors lack selectivity for the various HDAC isoenzymes. Here, we describe our protocol for the discovery of novel potential hydroxamic acid based HDAC3 inhibitors through pharmacophore modeling, virtual screening, docking, molecular dynamics (MD) simulation and toxicity studies. The ten pharmacophore hypotheses were established, and their reliability was validated by different ROC (receiving operator curve) analysis. Among them, the best model (Hypothesis 9 or RRRA) was employed for searching SCHEMBL, ZINC and MolPort database to screen out hit molecules as selective HDAC3 inhibitors, followed by different docking stages. MD simulation (50 ns) and MMGBSA study were performed to study the stability of ligand binding modes and with the help of trajectory analysis, to calculate the ligand-receptor complex RMSD (root-mean-square deviation), RMSF (root-mean-square fluctuation) and H-bond distance, etc. Finally, in-silico toxicity studies were performed on top screened molecules and compared with reference drug SAHA and established structure-activity relationship (SAR). The results indicated that compound 31, with high inhibitory potency and less toxicity (probability value 0.418), is suitable for further experimental analysis.Communicated by Ramaswamy H. Sarma.

Pharmacophore modeling and virtual screening were performed with hydroxamic acid derivatives as HDAC3 inhibitors.MD simulation was performed for 50 ns time duration for selected protein-ligand complexes.SAR and toxicity studies (using TOPKAT tool) were performed.The results of these studies might be valuable in the further design and development of more potent HDAC3 inhibitors.

α-Tocopherol Polyethylene Glycol 1000 Succinate-Based Cationic Liposome for the Intracellular Delivery of Doxorubicin in MDA-MB-231 Triple-Negative Breast Cancer Cell Line.

Present research work reports the development of doxorubicin (DOX) loaded α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes. The developed formulation was evaluated for its anticancer potential and intracellular uptake against the MDA-MB-231 breast cancer cell line. Moreover, hemocompatibility studies were also done on human blood red blood cells for the determination of blood compatibility. The prepared doxorubicin-loaded TPGS liposomes (DOX-LIPO-TPGS) and doxorubicin-loaded cationic liposomes (DOX-LIPO+-TPGS) reveal vesicle size (177.5 ± 2.5 and 201.7 ± 2.3 nm), polydispersity index (0.189 ± 0.01 and 0.218 ± 0.02), zeta potential (-36.9 ± 0.7 and 42 ± 0.9 mv), and % entrapment efficiency (65.88% ± 3.7% and 74.5% ± 3.9%). Furthermore, in vitro, drug release kinetics of the drug alone and drug from formulation shows sustained release behavior of developed formulation with 99.98% in 12 h and 80.98% release of the drug in 72 h, respectively. In addition, cytotoxicity studies and cellular DOX uptake on the MDA-MB-231 breast cancer cell line depict higher cytotoxic and drug uptake potential with better hemocompatibility of DOX-LIPO+-TPGS with respect to DOX. The data from the study revealed that TPGS plays an important role in enhancing the formulation's quality attributes like stability, drug release, cytotoxicity, and hemocompatibility behavior. This may serve that TPGS-coated cationic liposome as a vital candidate for the treatment of cancer and drug delivery in case of breast cancer.

Quality by design-assisted development of D-α-tocopherol polyethylene glycol 1000 succinate-incorporated gefitinib-loaded cationic liposome(s).

Aim: Gefitinib-loaded D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes (GEF-TPGS-LIPO+) were developed and optimized by the quality by design (QbD) approach for its potential anticancer effect. Methods/materials: Box-Behnken design (BBD) a systematic design of experiments was added to screen and optimize the formulation variables. Results: GEF-TPGS-LIPO+ shows vesicle size (210 ± 4.82 nm), polydispersity index (0.271 ± 0.002), zeta potential (22.2 ± 0.84 mV) and entrapment efficiency (82.3 ± 1.95). MTT result shows the enhanced cytotoxicity and higher intracellular drug uptake with highest and lowest levels of the reactive oxygen species and NF-κB expressions on A549 lung cancer cells, determined by fluorescence-activated cell sorting flow cytometry. Conclusion: Potential anticancer effect on A549 cells might be found due to cationic liposomal interaction with cancer cells.