Liposomal Formulation Research Articles

Enhancing glioblastoma cytotoxicity through encapsulating O6-benzylguanine and temozolomide in PEGylated liposomal nanocarrier: an in vitro study

Glioblastoma (GBM) (grade IV glioma) is the most fatal brain tumor, with a median survival of just 14 months despite current treatments. Temozolomide (TMZ), an alkylating agent used with radiation, faces challenges such as systemic toxicity, poor absorption, and drug resistance. To enhance TMZ effectiveness, we developed poly(ethylene glycol) (PEG) liposomes co-loaded with TMZ and O6-benzylguanine (O6-BG) for targeted glioma therapy. These liposomes, prepared using the thin-layer hydration method, had an average size of 146.33 ± 6.75 nm and a negative zeta potential (−49.6 ± 3.1 mV). Drug release was slower at physiological pH, with 66.84 ± 4.62% of TMZ and 69.70 ± 2.88% of O6-BG released, indicating stability at physiological conditions. The liposomes showed significantly higher cellular uptake (p < 0.05) than the free dye. The dual drug-loaded liposomes exhibited superior cytotoxicity against U87 glioma cells, with a lower IC50 value (3.99µg/mL) than the free drug combination, demonstrating enhanced anticancer efficacy. The liposome formulation induced higher apoptosis (19.42 ± 3.5%) by causing sub-G0/G1 cell cycle arrest. The novelty of our study lies in co-encapsulating TMZ and O6-BG within PEGylated liposomes, effectively overcoming drug resistance and improving targeted delivery for glioma treatment.

Synthesis of gold nanoparticles using soybean byproducts: applications in catalysis

AbstractThis study demonstrates the feasibility of extracting lecithin from oil industry byproducts in an eco‐friendly manner, with minimal use of water and without harmful chemicals. Liposomes can be generated directly from this extracted lecithin, enhancing the value of these byproducts and enabling the production of catalytic gold nanoparticles (AuNPs). Thin‐layer chromatography of the extracted lecithin revealed a phospholipid composition primarily consisting of phosphatidylethanolamine and phosphatidylcholine, and surface tension studies demonstrated similar behavior between the extracted and commercial lecithin. Liposome formation using sustainable lecithin (LPn) resulted in structures that were stable for at least 10 days, exhibiting a low polydispersity index (0.395) and uniform size (approximately 214 ± 7 nm). Gold nanoparticles were synthesized successfully in LPn loaded with [HAuCl4] by using different photoreduction methods: ultraviolet (UV) lamp, pulsed laser 355 nm, and sunlight irradiation. The AuNPs exhibited characteristic sizes (ranging from 5.03 to 6.78 nm) and optical properties typical of nanoparticles, including a distinct surface plasmon resonance. As a proof of concept, we also demonstrated that the synthesized AuNPs exhibited catalytic activity in UV‐induced cis‐trans isomerization reactions. Overall, the study highlights the potential of sustainable soy lecithin extraction for diverse applications, including nanoparticle synthesis and catalysis.

Single-Dose Physically Cross-Linked Hyaluronic Acid and Lipid Hybrid Nanoparticles Containing Cyclic Guanosine Monophosphate-Adenosine Monophosphate Eliminate Established Tumors.

Activating the STING pathway in the cytosol of tumor-infiltrating antigen-presenting cells (APCs) represents a promising strategy to elicit potent antitumor immune responses for cancer therapy. However, STING agonists are mostly small hydrophilic molecules that suffer from rapid clearance and poor cytosolic delivery following systemic administration. While various nanoparticles have been developed to promote cytosolic delivery, they often exhibit premature drug release during circulation. Alternatively, stable nanoparticles with sustained release during circulation have poor cytosolic delivery. In this study, we have developed physically cross-linked hyaluronic acid (HA) and lipid hybrid nanoparticles containing cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), denoted as HLHC, to address these challenges. The HLH delivery system has sustained drug release due to multiple lipid layers physically cross-linked by HA. HLHC efficiently delivers cGAMP to the cytosol of APCs, inducing more IFNβ than cGAMP and liposomal cGAMP. HLH also improves the drug circulation time and biodistribution to the tumor compared with the liposomal formulation and free drug. Strikingly, a single dose of HLHC, but not liposomal cGAMP or free cGAMP, elicits potent antitumor immunity and regresses established MC38 tumors. A single dose of HLHC even regresses established B16F10 tumors upon combination with αPD-L1. Moreover, cured animals were protected from rechallenge with the same tumor cells. HLHC represents an efficient strategy to address delivery challenges associated with STING agonists and may have broad applications for the delivery of drugs acting in the cytosol.

Preparation of New Liposomal Daunorubicin and Evaluation of its Anti-colorectal Cancer in HCT116 Cells

Background: Colorectal cancer (CRC) is the third most common cause of cancerrelated deaths worldwide. To develop more effective anti-CRC drugs, this research evaluated the impact of synthesized liposomal daunorubicin on HTC116 colon cancer cell line. Methods: Liposomal daunorubicin (LDNR) was synthesized by the thin layer hydration method and size was determined by dynamic light diffraction (DLS). MTT assay was used to determine the cytotoxicity and IC50 of LDNR against the HCT116 CRC cell line. Relative mRNA expression of the NF-κB gene and apoptosis were evaluated in 24 hours treatments of HCT116 cells by qRT-PCR and flow cytometry, respectively. Results: The hydrodynamic diameter of liposomes containing daunorubicin (DNR) was determined 25.2 nm. MTT assay showed a 38% decrease in HCT116 cells viability after 24-hour treatment with the DNR (0.5 μM). The lowest (0.125 μM) and highest (2 μM) dose of LDNR showed 20.4% and 71.6% cytotoxicity, respectively. LDNR showed dose-dependent cytotoxicity with the IC50 of 0.87 μM. The phase contrast microscope evaluation confirmed the LDNR cytotoxicity. The DNR and LDNR (0.87 μM) decreased relative mRNA levels of NF-κB 63% (P= 0.023) and 99.6% (P=0.003), respectively. The percentage of apoptotic cells in the DNR and LDNR increased by 27.1% (P&lt;0.0001) and 49.7% (P&lt;0.0001), respectively. Conclusion: DNR increases the rate of apoptosis by decreasing the NF-κB gene expression in HCT116 cells. These effects are intensified in the liposomal form. Therefore, the LDNR produced in this research can be considered in the treatment of CRC.

A DNA Origami Bubble Blower for Liposome Production.

While liposomes are commonly produced on the industrial scale with diameters in the hundreds of nanometers to micrometer size range, the variation from the mean diameter can be significant. In nature, functional liposome-like systems can be as small as tens of nanometers in diameter but reproducible synthetic production at this size scale is not easily achievable. Here we outline the development of a DNA origami "bubble blower"-a nanoscale ring able to seed and constrain liposome formation. The bubble blower has the potential to be employed in a reusable fashion for production of nanometric liposomes. It improves currently available DNA origami liposome seeding techniques by expanding the range of compatible detergents and introducing solid support integration with potential for semiautomated laboratory scale production.

Enhancing Gentamicin Antibacterial Activity by Co-Encapsulation with Thymoquinone in Liposomal Formulation

Background and Purpose. Gentamicin (GEN) is a broad-spectrum antibiotic that cannot be prescribed freely because of its toxicity. Thymoquinone (THQ), a phytochemical, has antibacterial, antioxidant, and toxicity-reducing properties. However, its hydrophobicity and light sensitivity make it challenging to utilize. This incited the idea of co-encapsulating GEN and THQ in liposomes (Lipo-GEN-THQ). Method. Lipo-GEN-THQ were characterized using the zeta-potential, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscope (TEM). The liposomes’ stability was evaluated under different storage and biological conditions. Lipo-GEN-THQ’s efficacy was investigated by the minimum inhibitory/bactericidal concentrations (MICs-MBCs), time–kill curves, and antibiofilm and antiadhesion assays. Bacterial interactions with the empty and GEN-THQ-loaded liposomes were evaluated using TEM. Results. The Lipo-GEN-THQ were spherical, monodispersed, and negatively charged. The Lipo-GEN-THQ were relatively stable and released GEN sustainably over 24 h. The liposomes exhibited significantly higher antibacterial activity than free GEN, as evidenced by the four-fold lower MIC and biofilm eradication in resistant E. coli strain (EC-219). TEM images display how the empty liposomes fused closely to the tested bacteria and how the loaded liposomes caused ultrastructure damage and intracellular component release. An antiadhesion assay showed that the Lipo-GEN-THQ and free GEN (0.125 mg/L) similarly inhibited Escherichia coli (EC-157) adhesion to the A549 cells (68% vs. 64%). Conclusions. The Lipo-THQ-GEN enhanced GEN by combining it with THQ within the liposomes, reducing the effective dose. The reduction in the GEN dose after adding THQ may indirectly reduce the toxicity and aid in developing an enhanced and safer form of GEN.

Development and in vitro characterization of new carnosine-loaded liposomal formulations.

Carnosine is an endogenous dipeptide characterized by a multimodal mechanism of action. However, its clinical potential is limited by serum and cytosolic carnosinases, which significantly reduce its bioavailability. Based on that, different research groups have worked on the development of new strategies able not only to prevent its rapid metabolization but also to improve its distribution and specific targeting. In the present study, the development and in vitro characterization of new liposomal formulations loaded with carnosine are described. Nanoliposomes, produced through Thin-Layer Hydration followed by Extrusion method, were first investigated for their physicochemical stability. Photon correlation spectroscopy and electrophoretic light scattering, assessing the stability of the formulations, showed a strong homogeneity-oriented tendency for up to two months. Particle size, polydispersity index, and zeta potential were determined through dynamic light scattering and electrophoretic light scattering, demonstrating an almost neutral charge of the formulation and an effective encapsulation of carnosine. The morphology assessment performed via scanning electron microscopy showed good conformity and polydispersity. Differential scanning calorimetry measurements suggest the ability of carnosine to stabilize the large unilamellar vesicles. Lastly, the newly developed carnosine-loaded liposomal formulations also showed a good safety profile in human microglia.

Small-Molecule Therapeutics Achieve Multiple Mechanism-Mediated Sensitizations of Colorectal Cancer to Immune Checkpoint Blockade via Neutrophil Micropharmacies.

Immune checkpoint blockade (ICB) therapy has been approved for colorectal cancer (CRC). However, response rates are variable and often <50%. The low tumor immunogenicity and immunosuppressive tumor microenvironment (TME) jointly contribute to this suboptimal response rate. This study confirmed the potential of combining immunogenic cell death (ICD) inducer irinotecan (IRI) and transforming growth factor-β (TGF-β) inhibitor galunisertib (GAL) to improve tumor immunogenicity and remodel the immunosuppressive TME. Moreover, to ameliorate the in vivo delivery barriers associated with small molecules, neutrophil micropharmacies (NOG) were developed for the codelivery of IRI and GAL, which loaded the commercial liposome formulation of IRI (ONIVYDE, ONI) intracellularly and conjugated the pH-responsive GAL liposome (GLP) on the cell surface. This neutrophil-based formulation resulted in a >4-fold increase in the ratios of the amount of both IRI and GAL accumulated in tumors to the dosage administration, effectively achieving multiple mechanism-mediated sensitization of CRC to ICB therapy.

A Mechanical Immune Checkpoint Inhibitor Stiffens Tumor Cells to Potentiate Antitumor Immunity.

Tumor progression is associated with tumor-cell softening. Improving the stiffness of the tumor cells can make them more vulnerable to lymphocyte-mediated attack. Tumor cell membranes typically exhibit higher cholesterol levels than normal cells, making tumor cells soft. Herein, we demonstrate a mechanical immune checkpoint inhibitor (MICI) formulated by cyclodextrin (CD) lipids and fusogenic lipids. Through fusing CD lipids into the tumor cell membrane using a fusogenic liposome formulation, the cholesterol in the plasma membrane is reduced due to the specific host-guest interactions between CD lipid and cholesterol. As a result, tumor cells are stiffened, and the activation of lymphocytes (including NK and cytotoxic effector T cells) is improved when contacting the stiffened tumor cells, characterized by robust degranulation and effector cytokine production. Notably, this treatment has negligible influence on the infiltration and proliferation of lymphocytes in tumor tissues, confirming that the enhanced antitumor efficacy should result from activating a specific number of lymphocytes caused by direct regulation of the tumor cell stiffness. The combination of MICIs and clinical immunotherapies enhances the lymphocyte-mediated antitumor effects in two tumor mouse models, including breast cancer and melanoma. Our research also reveals an unappreciated mechanical dimension to lymphocyte activation.

A Mechanical Immune Checkpoint Inhibitor Stiffens Tumor Cells to Potentiate Antitumor Immunity

Tumor progression is associated with tumor‐cell softening. Improving the stiffness of the tumor cells can make them more vulnerable to lymphocyte‐mediated attack. Tumor cell membranes typically exhibit higher cholesterol levels than normal cells, making tumor cells soft. Herein, we demonstrate a mechanical immune checkpoint inhibitor (MICI) formulated by cyclodextrin (CD) lipids and fusogenic lipids. Through fusing CD lipids into the tumor cell membrane using a fusogenic liposome formulation, the cholesterol in the plasma membrane is reduced due to the specific host–guest interactions between CD lipid and cholesterol. As a result, tumor cells are stiffened, and the activation of lymphocytes (including NK and cytotoxic effector T cells) is improved when contacting the stiffened tumor cells, characterized by robust degranulation and effector cytokine production. Notably, this treatment has negligible influence on the infiltration and proliferation of lymphocytes in tumor tissues, confirming that the enhanced antitumor efficacy should result from activating a specific number of lymphocytes caused by direct regulation of the tumor cell stiffness. The combination of MICIs and clinical immunotherapies enhances the lymphocyte‐mediated antitumor effects in two tumor mouse models, including breast cancer and melanoma. Our research also reveals an unappreciated mechanical dimension to lymphocyte activation.

A Comprehensive Review of Challenges in Oral Drug Delivery Systems and Recent Advancements in Innovative Design Strategies.

The oral route of drug administration is often preferred by patients and healthcare providers due to its convenience, ease of use, non-invasiveness, and patient acceptance. However, traditional oral dosage forms have several limitations, including low bioavailability, limited drug loading capacity, and stability and storage issues, particularly with solutions and suspensions. Over the years, researchers have dedicated considerable effort to developing novel oral drug delivery systems to overcome these limitations. This review discusses various challenges associated with oral drug delivery systems, including biological, pharmaceutical, and physicochemical barriers. It also explores common delivery approaches, such as gastroretentive drug delivery, small intestine drug delivery, and colon-targeting drug delivery systems. Additionally, numerous strategies aimed at improving oral drug delivery efficiency are reviewed, including solid dispersion, absorption enhancers, lipidbased formulations, nanoparticles, polymer-based nanocarriers, liposomal formulations, microencapsulation, and micellar formulations. Furthermore, innovative approaches like orally disintegrating tablets (ODT), orally disintegrating films (ODF), layered tablets, micro particulates, self-nano emulsifying formulations (SNEF), and controlled release dosage forms are explored for their potential in enhancing oral drug delivery efficiency and promoting patients' compliance. Overall, this review highlights significant progress in addressing challenges in the pharmaceutical industry and clinical settings, offering novel approaches for the development of effective oral drug delivery systems.

Development and In vitro and In vivo efficacy investigation of multifunctional, targeted, theranostic liposomes for imaging and photodynamic therapy of glioblastoma

The challenge of effectively diagnosing and treating glioblastoma, which has a high incidence and low survival rate, remains unresolved. Consequently, research efforts have increased to develop specific and effective diagnostic and therapeutic agents. In this study, N-acetyl glucosamine-modified, IR780-encapsulated, PEG-coated, nanosized, 68Ga-labeled, neutral, and positively charged theranostic liposomes were developed for GLUT1 targeting for PET/CT and NIR imaging and PDT/PTT of GBM. Characterization, in vitro release profile, stability, radiolabeling efficiency, and labeling stability were evaluated. In vitro cell uptake studies were conducted in RG2 and U87 GBM cell lines, NIR images were obtained in the RG2 and U87 cell lines, and fluorescence microscope images were obtained in the RG2 cell line. PDT/PTT activities were assessed after exposure to NIR light (808 nm, 0.8–1 W/cm2). Cytotoxicity was studied in RG2, U87, and L929 cell lines. In vivo studies were performed in GBM model nude mice. The liposomes had an optimum mean particle size (181–193 nm), high encapsulation efficiency (79–84 %), and zeta potential (−5 to −7 mV). The maximum 68Ga labeling efficiency was achieved with an incubation at 80 °C, pH: 3.5, and 5 min. Liposomes remained stable for 30 days at 4 °C. While the intracellular uptake of targeted formulations was higher than non-targeted ones, it was similar for positively charged and neutral formulations. In U87 and RG2 cell lines, cell viability remained above 50 % for liposomal formulations at a concentration of 1.5 μg/mL exposed to NIR light (808 nm, 0.8–1 W/cm2). The formulations showed significant PDT/PTT activity under NIR light and lower cytotoxicity in the L929 than in RG2 and U87 cell lines. In vivo bioluminescence images and biodistribution studies in U87 tumor-bearing nude mice revealed higher tumor uptake of targeted, IR780-encapsulated liposomal formulations in tumor tissue compared to non-targeted ones. Liposomal formulations showed higher tumor uptake than the free IR780 solution. The data suggest that targeted liposomes have potential as theranostic agents for PDT/PTT and multifunctional glioblastoma imaging.

Liposomal Nanoformulation-encapsulated Paclitaxel for Reducing Chemotherapy Side Effects in Lung Cancer Treatments: Recent Advances and Future Outlooks.

Paclitaxel is one notable chemotherapy drug that is used to treat a number of cancers, including lung cancer. Nevertheless, it has drawbacks such as toxicity, low solubility in water, and the emergence of multidrug resistance (MDR). This article reviews the use of liposomal formulations to improve paclitaxel administration and efficacy for lung cancer therapy. Paclitaxel's pharmacological characteristics can be improved by liposomes through increased solubility, extended circulation, passive tumor targeting through leaky vasculature, and decreased side effects. Recent developments in paclitaxel liposomal formulations, including as cationic liposomes, conventional liposomes, targeted liposomes with particular ligands, and liposome-loaded microorganisms, are outlined in this article. In comparison to free paclitaxel, these nanoformulations exhibit enhanced cytotoxicity, cellular uptake, apoptosis, tumor growth suppression, and anticancer effects in lung cancer cell lines and animal models. One efficient way to get around the drawbacks of paclitaxel is to alter its size, makeup, and surface characteristics. This will let the medication accumulate and penetrate tumors more easily, avoid multidrug resistance, and cause less systemic toxicity. The article explores clinical studies showcasing the safety and therapeutic efficacy of liposomal paclitaxel for individuals afflicted with lung cancer. In its entirety, the document provides an in-depth examination of the potential enhancement in paclitaxel's dispersion and anti-tumor impacts through the utilization of liposomal technology when addressing diverse manifestations of lung cancer.

Targeted Cancer Therapy: The Role of Liposomes in Oncology. A Literature Review

Liposomal formulations represent a significant advancement in the field of oncology, providing innovative solutions for the delivery of chemotherapeutic agents. These nanoscale carriers, made of phospholipid bilayers, enhance drug stability and allow for targeted delivery to tumor tissues, thereby improving the therapeutic index of anticancer medications. By altering the pharmacokinetics and biodistribution of these drugs, liposomes help reduce systemic side effects while increasing the concentration of therapeutic agents at the tumor site. Recent developments in liposomal technology have led to the creation of targeted liposomes, which can bind specifically to cancer cells, enhancing treatment accuracy. This review examines the various applications of liposomes in cancer treatment, discusses important clinical trials, identifies challenges in formulation and delivery, and considers future directions for integrating liposomal therapies into routine oncology practice. As ongoing research progresses, liposomes are poised to play a crucial role in advancing cancer treatment strategies and improving patient outcomes. Additionally, we discuss the challenges associated with their clinical translation and future perspectives in optimizing liposome formulations for personalized cancer therapies.

Smart Accumulating Dual-Targeting Lipid Envelopes Equipping Oncolytic Adenovirus for Enhancing Cancer Gene Therapeutic Efficacy.

Systemic delivery of oncolytic adenovirus (oAd) for cancer gene therapy must overcome several limitations such as rapid clearance from the blood, nonspecific accumulation in the liver, and insufficient delivery to the tumor tissues. In the present report, a tumor microenvironment-triggered artificial lipid envelope composed of a pH-responsive sulfamethazine-based polymer (PUSSM)-conjugated phospholipid (DOPE-HZ-PUSSM) and another lipid decorated with epidermal growth factor receptor (EGFR) targeting peptide (GE11) (GE11-DOPE) was utilized to encapsulate replication-incompetent Ad (dAd) or oAd coexpressing short-hairpin RNA (shRNA) against Wnt5 (shWnt5) and decorin (dAd/LP-GE-PS or oAd/LP-GE-PS, respectively). In vitro studies demonstrated that dAd/LP-GE-PS transduced breast cancer cells in a pH-responsive and EGFR-specific manner, showing a higher level of transduction than naked Ad under a mildly acidic pH of 6.0 in EGFR-positive cell lines. In vivo biodistribution analyses revealed that systemic administration of oAd/LP-GE-PS leads to a significantly higher level of intratumoral virion accumulation compared to naked oAd, oAd encapsulated in a liposome without PUSSM or EGFR targeting peptide moiety (oAd/LP), or oAd encapsulated in a liposome with EGFR targeting peptide alone (oAd/LP-GE) in an EGFR overexpressing MDA-MB-468 breast tumor xenograft model, showing that both pH sensitivity and EGFR targeting ability were integral to effective systemic delivery of oAd. Further, systemic administration of all liposomal oAd formulations (oAd/LP, oAd/LP-GE, and oAd/LP-GE-PS) showed significantly attenuated hepatic accumulation of the virus compared to naked oAd. Collectively, our findings demonstrated that pH-sensitive and EGFR-targeted liposomal systemic delivery of oAd can be a promising strategy to address the conventional limitations of oAd to effectively treat EGFR-positive cancer in a safe manner.

Development and optimization of an in vitro release assay for evaluation of liposomal irinotecan formulation

Onivyde®, a pegylated irinotecan liposomal formulation, is approved by the USFDA for treating metastatic pancreatic adenocarcinoma. Despite the substantial interest in developing its generic versions, the unique structural and manufacturing complexities of liposomal formulations pose challenges. In this study, we address this gap by developing a robust in vitro release test (IVRT) using dialysis membrane techniques. The release of Onivyde® is influenced by several key factors, including the composition of the release medium, temperature, initial formulation concentration, the materials and molecular weight cut-offs of dialysis bags, and the pH of the release medium. Our optimized IVRT for Onivyde® incorporates a release medium containing 5 mM ammonium bicarbonate in a HEPES solution with a pH of 7.4. Additionally, the method includes an initial formulation concentration of 4.6 µg/mL and 50 kDa dialysis bags, while maintaining a temperature of 37 °C with continuous agitation at 80 rpm. This optimized IVR assay effectively differentiates between varying qualities of irinotecan liposomal formulations. Our findings contribute to optimizing IVRT for liposomal irinotecan formulations, enabling better quality control procedures. This assay serves as a reliable tool for evaluating generic irinotecan liposomal formulations, aiding in their development and ensuring in vitro comparability.

In vitro characterization of beta-cyclodextrin liposomal formulation of cisplatin nanomedicine

This study aims to develop a nanomedicine-based approach to protect healthy tissue during cancer treatment, improve patient compliance, reduce adverse drug reactions, and enhance the quality of life. By utilizing hydroxypropyl-β-cyclodextrin (BPCP) to increase drug hydrophilicity and liposomes for controlled release of cisplatin (CP), the hydroxypropyl-β-cyclodextrin-cisplatin liposomal formulation (BCDCPLP) demonstrated improved stability, targeted delivery, and reduced toxicity. The study confirmed that the above formulation had the highest cytotoxicity against HeLa cells, with significantly lower IC50 and IC90 values than cisplatin alone. This is attributed to improved drug stability and cellular uptake. Caspase-3 and cleaved PARP assays confirmed that BCDCPLP and CP-loaded liposomes induced substantial apoptosis, with BCDCPLP showing the highest increase in caspase-3 activity and PARP cleavage at 85 kDa. The ability of BCDCPLP to enhance apoptosis was further demonstrated through Western blot analysis, where the density of PARP cleavage bands was highest in BCDCPLP-treated cells, followed by CPLP and CP-treated cells. The study highlights that the cumulative release of PARP from CP-nanocarrier complexes leads to more efficient apoptosis than free CP. These findings align with the synergistic effects observed when combining CP with PARP inhibitors, which induce mitochondrial membrane permeabilization and cytochrome C release, activating the intrinsic apoptosis pathway. The potential of these nanomedicines, especially BCDCPLP, is in reducing the required dosage while maintaining therapeutic efficacy offers promising advances in cancer therapy.

Cellular uptake of CPX-351 by scavenger receptor class B type 1-mediated nonendocytic pathway

The proper uptake of drugs in liposome formulations into target cells markedly impacts therapeutic efficacy. The protein corona (PC), formed by the adsorption of serum proteins onto the liposome surface, binds to specific surface receptors of target cells, influencing the uptake pathway. We investigated the uptake pathway into leukemia cells based on PC analysis of CPX-351, a liposome containing cytarabine and daunorubicin in a fixed 5:1 synergistic molar ratio. The PC of CPX-351 mixed with fetal bovine serum was analyzed by nanoflow liquid chromatography-tandem mass spectrometry. CPX-351 uptake in HL-60, K562, and THP-1 leukemia cell lines, was measured by flow cytometry using daunorubicin fluorescence. The major components of CPX-351 PC were apolipoproteins A-I and A-II, which bind to scavenger receptor class B type 1 (SR-BI), a nonendocytic pathway that takes up only liposome contents. SR-BI was expressed in each cell, and its expression correlated with CPX-351 uptake. The uptake was significantly decreased by the inhibition of clathrin-mediated endocytosis and macropinocytosis. Additionally, blocks lipid transport-1 (BLT-1), a selective inhibitor of SR-BI, decreased the uptake; however, high-dose BLT-1 addition significantly increased the uptake, which was more strongly inhibited by macropinocytosis suppression compared with clathrin-mediated endocytosis. BLT-1 enhances the binding of SR-BI to liposomes in a dose-dependent manner. These findings indicate that the enhancement of binding between SR-BI and CPX-351 activates different pathways, such as macropinocytosis, distinct from CPX-351 alone. SR-BI may be a biomarker for CPX-351 therapy, and the combination of CPX-351 with high-dose BLT-1 may augment therapeutic efficacy.

Cisplatin-based Liposomal Nanocarriers for Drug Delivery in Lung Cancer Therapy: Recent Progress and Future Outlooks.

In order to improve the treatment of lung cancer, this paper looks at the development of cisplatinbased liposomal nanocarriers. It focuses on addressing the drawbacks of conventional cisplatin therapy, including systemic toxicity, inadequate tumor targeting, and drug resistance. Liposomes, or spherical lipid vesicles, offer a potentially effective way to encapsulate cisplatin, enhancing its transport and minimizing harmful effects on healthy tissues. The article discusses many liposomal cisplatin formulations, including pH-sensitive liposomes, sterically stabilized liposomes, and liposomes coupled with specific ligands like EGFR antibodies. These novel formulations show promise in reducing cisplatin resistance, optimizing pharmacokinetics, and boosting therapeutic results in the two in vitro and in vivo models. They also take advantage of the Enhanced Permeability and Retention (EPR) effect in the direction of improved tumor accumulation. The study highlights the need for more investigation to move these liposomal formulations from experimental to clinical settings, highlighting their potential to offer less harmful and more effective cancer therapy alternatives.

Curcumin Nanostructured Drug Delivery Induces the Anti-cancer and Anti-inflammatory activity In Vitro and In Vivo

Background: The therapeutic potential of plant-derived pharmaceuticals is often limited by poor bioavailability and rapid metabolism. This study aims to enhance the pharmacological effects of curcumin, a bioactive compound from plants, through the development of novel drug delivery systems (NDDS). Methods: Various NDDS, including liposomes, nanoparticles, and microspheres, were formulated to encapsulate curcumin. We evaluated their drug release characteristics, encapsulation efficiency, and particle size in vitro. The pharmacological effectiveness of these formulations was assessed using cytotoxicity assays on human cancer cell lines and anti-inflammatory models in rats. Results: The liposomal formulation achieved an encapsulation efficiency of 85% with an average particle size of 150 nm. The nanoparticle and microsphere formulations demonstrated encapsulation efficiencies of 78% and 90%, with particle sizes of 200 nm and 10 µm, respectively. All formulations exhibited a sustained release profile, with 70% of curcumin released over 24 hours. Cytotoxicity studies revealed that the NDDS formulations significantly increased cell death in cancer cells, with the liposomal formulation showing a 50% increase in apoptosis. In vivo experiments indicated a 60% reduction in paw edema with the nanoparticle formulation compared to the control group, highlighting enhanced anti-inflammatory effects. Conclusion: The findings of this study suggest that NDDS significantly improve the encapsulation efficiency, sustained release, and pharmacological activity of curcumin. This approach demonstrates the potential of NDDS to enhance the clinical efficacy of plant-derived drugs, leading to improved therapeutic outcomes.