Liposomal System Research Articles

Preparation, characterization, in vitro and in vivo studies of liposomal berberine using novel natural Fiber Interlaced Liposomal technology

Berberine hydrochloride (BBR), used in various traditional medicinal practices, has a variety of pharmacological effects. It is a plant-derived quaternary isoquinoline alkaloid with a low water solubility and can be used in the treatment of various conditions. However, the therapeutic use of BBR has been compromised because of its hydrophobic characteristics, in addition to its low stability and poor bioavailability. To overcome these drawbacks of BBR’s oral bioavailability, technologies like liposomal delivery systems have been developed to ensure enhanced absorption. But conventional liposomes have low physical and chemical stability due to delicate liposomal membranes, peroxidation and rapid clearance from the bloodstream. Surface modification of liposomes could be a solution and creating a liposome with plant-based fibers as surface material will provide enhanced stability, aqueous solubility and protection against degradation. Consequently, the aim of this study is to create and describe a Fiber Interlaced Liposome™ (FIL) as a vehicle for an enhanced bioavailability platform for BBR and other biomolecules. This optimised FIL-BBR formulation was analysed for its structural and surface morphological characteristics by using FTIR, SEM, TEM, XRD, zeta potential and DSC. Encapsulation efficiency, stability, and sustained release studies using an in vitro digestion model with simulated gastric and intestinal fluids were also examined. FIL formulation showed a sustained release of BBR at 59.03 % as compared to the unformulated control (46.73 %) after 8 h of dialysis. Furthermore, the FIL-BBR demonstrated enhanced stability in the simulated gastric fluid (SGF) in addition to a more sustained release in the simulated intestinal fluid (SIF). The efficacy of FIL-BBR were further anlaysed by an in vivo bioavailability study using male Wistar rats and it demonstrated a 3.37−fold higher relative oral bioavailability compared to the unformulated BBR. The AUC 0-t for BBR in FIL-BBR was 1.38 ng.h/mL, significantly greater than the unformulated BBR (0.41 ng.h/mL). Similarly, the Cmax for BBR in FIL-BBR (50.98 ng/mL) was discovered to be far greater than unformulated BBR (15.54 ng/mL) after the oral administration. These findings imply that fruit fiber based liposomal encapsulation improves the stability and slows down BBR release, which could be advantageous for applications requiring a higher bioavailability and a more sustained release.

Targeted delivery of bee venom to A549 lung cancer cells by PEGylate liposomal formulation: an apoptotic investigation

This study focused on developing an optimal formulation of liposomes loaded with bee venom (BV) and coated with PEG (BV-Lipo-PEG). The liposomes were characterized using dynamic light scattering, transmission electron microscopy, and Fourier transform infrared spectroscopy. Among the liposomal formulations, F3 exhibited the narrowest size distribution with a low PDI value of 193.72 ± 7.35, indicating minimal agglomeration-related issues and a more uniform size distribution. BV-Lipo-PEG demonstrated remarkable stability over 3 months when stored at 4 °C. Furthermore, the release of the drug from the liposomal formulations was found to be pH-dependent. Moreover, BV-Lipo-PEG exhibited favorable entrapment efficiencies, with values reaching 96.74 ± 1.49. The anticancer potential of the liposomal nanocarriers was evaluated through MTT assay, flow cytometry, cell cycle analysis, and real-time experiments. The functionalization of the liposomal system enhanced endocytosis. The IC50 value of BV-Lipo-PEG showed a notable decrease compared to both the free drug and BV-Lipo alone, signifying that BV-Lipo-PEG is more effective in inducing cell death in A549 cell lines. BV-Lipo-PEG exhibited a higher apoptotic rate in A549 cell lines compared to other samples. In A549 cell lines treated with BV-Lipo-PEG, the expression levels of MMP-2, MMP-9, and Cyclin E genes decreased, whereas the expression levels of Caspase3 and Caspase9 increased. These findings suggest that delivering BV via PEGylated liposomes holds significant promise for the treatment of lung cancer.

Influence of archaeal lipids isolated from Aeropyrum pernix K1 on physicochemical properties of sphingomyelin-cholesterol liposomes

We investigated the influence of archaeal lipids (C25,25) isolated from thermophilic archaeon Aeropyrum pernix K1 on physicochemical properties of liposomes comprised of egg sphingomyelin (SM) and cholesterol (CH) using fluorescence emission anisotropy, calcein release studies, dynamic light scattering, transmissive electron microscopy and phase analysis light scattering. The 2 mol% addition of archaeal lipids enabled formation of small unilamellar vesicles by sonication while also having significant effect on reducing mean size, polydispersity index and zeta potential of C25,25/SM/CH vesicles. Increasing the ratio of C25,25 lipids in mixture of C25,25/SM/CH decreased lipid ordering parameter in dose dependent manner at different temperatures. We also demonstrated that adding 15 mol% C25,25 to SM/CH mixture will cause it to notably interact with fetal bovine serum which could make them a viable alternative adjuvant to synthetic ether-linked lipids in development of advanced liposomal vaccine delivery systems. The prospect of combining the proven strengths of SM/CH mixtures with the unique properties of C25,25 opens exciting possibilities for advancing drug delivery technologies, promising to yield formulations that are both highly effective and adaptable to a range of therapeutic applications.

Therapeutic liposomal combination to enhance chemotherapy response and immune activation of tumor microenvironment

Multiple oxaliplatin-resistance mechanisms have been proposed such as increase of anti-inflammatory M2 macrophages and lack of cytotoxic T-cells. Thereby oxaliplatin chemotherapy promotes an immunosuppressive tumor microenvironment and inhibits anti-tumor efficacy. It has been shown that toll-like receptor (TLR) agonists are capable of triggering broad inflammatory responses, which may potentially reduce oxaliplatin-resistance and improve the efficacy of chemotherapy. In this study, we established colorectal tumor-bearing zebrafish and mice, and investigated the effects of TLR agonists and oxaliplatin in macrophage function and anti-tumor T cell immunity as well as tumor growth control in vivo. To increase the potential of this strategy as well minimize side effects, neutral liposomes carrying oxaliplatin and cationic liposomes co-loaded with TLR agonists Poly I:C and R848 were employed for maximum immune activation. Both of two liposomal systems exhibited good physicochemical properties and excellent biological activities in vitro. The combination strategy delivered by liposomes showed more pronounced tumor regression and correlated with decreased M2 macrophage numbers in both zebrafish and mice. Increasing numbers of dendritic cells, DC maturation and T cell infiltration mediated via immunogenic cell death were observed in treated mice. Our study offers valuable insights into the potential of liposomal combination therapy to improve cancer treatment by reprogramming the tumor microenvironment and enhancing immune responses.

Stabilization of cationic liposomes using hyaluronic acid-modified gold nanoparticles by post-microfluidics conjugation approach for drug delivery applications

lipid-based nanoparticles (LNPs), particularly liposomes, have gained prominence throughout the pharmaceutical sector as a hopeful means for transporting a range of therapeutic agents. Improving LNPs stability is crucial in pharmaceuticals, and drug delivery systems to ensure their effectiveness and reliability. The current research was undertaken to design a pH-responsive hyaluronic acid-modified gold nanoparticle-stabilized cationic liposome (SPC/DOPE/DOTAP) system (HA-SH/AuNPs@liposomes) to improve the stability of liposomes. This was achieved through a post-microfluidics conjugation technique to encapsulate the 5-fluorouracil (5-FU) anticancer drug, usually employed in nonmelanoma skin cancer (NMSC) treatment. Microfluidics is an emerging technology that can be employed as a powerful tool for designing nanoscale liposomes with highly uniform size distributions and acceptable colloidal stability. Utilizing a microfluidics toroidal mixer, affixed HA-SH/AuNPs (size: 12.56 ± 1.65 nm) to positively charged liposomes (size: 75 ± 0.68 nm and PDI: 0.032 ± 0.0021). These liposomes exhibited strong stability, limited fusion propensity, and minimal cargo release at neutral pH. The gold stabilizers detached in an acidic environment, releasing encapsulated therapeutic agents. The dynamic light scattering (DLS) analysis results indicate that HA-SH/AuNPs@Liposomes (size: 102.2 ± 1.3 nm and PDI: 0.11 ± 0.01) exhibit greater stability than bare liposomes over 4 weeks at 4 °C. This enhanced stability can be attributed to the presence of HA-SH/AuNPs in the liposomal structure. This research outlines a systematic method to optimize the size rapidly and PDI of liposomes by employing the Design of Experiments (DoE). The results highlighted that utilizing both the microfluidic technique and gold nanoparticle-stabilized liposomes offers benefits for creating controlled drug release formulations. This approach leads to enhanced biopharmaceutical characteristics and improved scalability of liposomal formulations.

Ion-Mediated Structural Discontinuities in Phospholipid Vesicles.

Despite intense research, methods for controlling soft matter's spontaneous self-assembly into well-defined layers remain a significant challenge. We observed ion-induced structural discontinuities of phospholipid vesicles that can be exploited for controlled self-assembly of soft materials, using DOPC and NaCl as a model system. The observations were made for the 0.25 wt % lipid concentration. We used dynamic light scattering, zeta-potential measurement, cryo-electron microscopy, small-angle X-ray, and small-angle neutron scattering to understand the reason for the discontinuities. For salt concentrations below 8 mM, we observed a decrease in the liposome diameter with increased NaCl concentration. Above 8 mM, we measured a discontinuity; the radius increases within a very narrow salt concentration range within less than 0.1 mM and then decreases for values greater than 8 mM. At 75 mM, the radius becomes constant until it grows again at around 500 mM. Microscopy and scattering experiments show a transition from unilamellar to bilamellar at 8 mM and to trilamellar at 75 mM. At 500 mM, we found a heterogeneous liposome system with many different bilayer numbers. All the experimental observations indicate that declining solvent quality and increasing osmotic pressure direct lipids to expel preferentially to the inner compartment. Upon reaching a critical concentration, excess lipids can form a new bilayer. This spontaneous self-assembly process causes simultaneous shrinkage of the aqueous core and expansion of the vesicle. This approach opens an intriguing path for controlling the self-assembly of bioinspired colloids.

Synergistic effects of thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy in breast cancer management: an orthotopic mouse model study.

Liposome formulations of the cancer drug doxorubicin have been developed to address the severe side effects that result from administration of this drug in a conventional formulation. Among them, thermosensitive liposomal doxorubicin presents enhanced tumor targeting and efficient drug release when combined with mild hyperthermia localized to the tumor site. Exploiting the radiosensitizing benefits of localized thermal therapy, the integration of radiation therapy with the thermally activated liposomal system is posited to amplify the anti-tumor efficacy. This study explored a synergistic therapeutic strategy that combines thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy, using an orthotopic murine model of breast cancer. The protocol of sequential multi-modal treatment, incorporating low-dose chemotherapy and radiotherapy, substantially postponed the progression of primary tumor growth in comparison to the application of monotherapy at elevated dosages. Improvements in unheated distant lesions were also observed. Furthermore, the toxicity associated with the combination treatment was comparable to that of either thermosensitive liposome treatment or radiation alone at low doses. These outcomes underscore the potential of multi-modal therapeutic strategies to refine treatment efficacy while concurrently diminishing adverse effects in the management of breast cancer, providing valuable insight for the future refinement of thermosensitive liposomal doxorubicin applications.

Immunological Activity of Vaccine Systems Containing Liposomal Nanocarriers against Protozoan-Induced Diseases: A Systematic Review.

Neglected parasitic diseases constitute a broad spectrum of clinical conditions that, in the chronic phase, lack effective therapies for the target population. The utilization of vaccines based on liposomal nanocarrier systems is emerging, thereby enhancing clinical outcomes in various comorbidities. Consequently, this study aims to assess the immunological activity induced by liposomal nanocarriers against neglected parasitic diseases. For the review, the Pubmed, Embase, and Lilacs databases were used using the descriptors vaccine, parasite, and liposome. The following inclusion criteria were adopted: in vivo and in vitro experimental articles. As exclusion criteria: book chapters, editorials, literature reviews and duplicate articles found during the database search. A total of 226 articles were identified, from which 34 were selected for review. The primary diseases identified included Babesia bovis, Entamoeba histolytica, Leishmania braziliensis, Leishmania donovani, Leishmania major, Leishmania infantum, Plasmodium falciparum, Plasmodium chabaudi, Plasmodium chabaudi, Plasmodium yoelii, Toxoplasma gondii and Trypanosoma cruzi. An elevation in cytokines such as GM-CSF, MCP-1, INF-γ, TNF-α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, and IL-17 was observed in the studies evaluated regarding the parasitic diseases. Furthermore, cytokines such as IL-4, IL-10, and TGF-β were diminished with the administration of the vaccine systems in those studies. Therefore, the administration of liposomal nanovaccine systems can effectively ameliorate the clinical condition of patients by modulating their immunological profile.

A Novel Inhalable Dry Powder to Trigger Delivery of Voriconazole for Effective Management of Pulmonary Aspergillosis.

Invasive pulmonary aspergillosis (IPA) is a fatal fungal infection with a high mortality rate. Voriconazole (VCZ) is considered a first-line therapy for IPA and shows efficacy in patients for whom other antifungal treatments have been unsuccessful. The objective of this study was to develop a high-potency VCZ-loaded liposomal system in the form of a dry-powder inhaler (DPI) using the spray-drying technique to convert liposomes into a nanocomposite microparticle (NCMP) DPI, formulated using a thin-film hydration technique. The physicochemical properties, including size, morphology, entrapment efficiency, and loading efficiency, of the formulated liposomes were evaluated. The NCMPs were then examined to determine their drug content, production yield, and aerodynamic size. The L3NCMP was formulated using a 1:1 lipid/L-leucine ratio and was selected for in vitro studies of cell viability, antifungal activity, and stability. These formulated inhalable particles offer a promising approach to the effective management of IPA.

Co-Encapsulation of Paclitaxel and Doxorubicin in Liposomes Layer by Layer

The synergistic effect of antineoplastic drug co-encapsulation systems has made them highly regarded due to their improved pharmacological efficacy. Biopolymer-coated liposomes were evaluated for paclitaxel and doxorubicin co-encapsulation in MCF-7 and MDA-MB-231 breast cancer cell lines. These nanosystems are characterized by dynamic light scattering, transmission electron microscopy, and UV–VIS spectroscopy. The conventional and hybrid liposomal systems presented sizes of 150 to 230 nm and %EE greater than 80% for the encapsulated active ingredients. These drug-laden liposomal systems significantly decreased cell viability in both breast cancer cell lines compared with liposome-free drugs. The delivery of antineoplastic drugs in breast cancer therapy could potentially benefit from new hybrids for drug co-encapsulation.

Dual-targeting liposomal delivery of sorafenib and docetaxel for enhanced synergistic therapy in advanced hepatocellular carcinoma

Patients with advanced hepatocellular carcinoma (HCC) are not sensitive to sorafenib (SOR), therefore, combination therapy is required. In this study, an improved thin-film dispersion and post-insertion anchoring technique was utilized to construct a dual-targeted co-delivery SOR and docetaxel (DTX) liposome drug delivery system, folate/chondroitin sulfate with SOR/DTX-modified liposomes (FA/CS@SDLP), to jointly enhance the anti-recurrence and metastasis of HCC. FA/CS@SDLP can establish the gradual release of the two drugs because of successful lysosomal escape in the condensed hyaluronidase environment. The results indicated that modification with folate (FA) and chondroitin sulfate (CS) significantly enhanced the cellular uptake of FA/CS@SDLP and the internalization of SOR/DTX in HepG2 cells through FA and CD44 receptor-mediated endocytosis. Compared to free drugs or the mono-targeted liposomal system (FA@SDLP), FA/CS@SDLP presented higher potency against HepG2 cells regarding pro-apoptosis, anti-proliferation, and anti-metastasis (migration and invasion). Moreover, a more satisfactory antitumor efficacy was observed for FA/CS@SDLP in the pulmonary metastasis of HCC in a mouse model. In summary, dual-targeted co-delivery of liposomes can synergistically treat HCC recurrence and metastasis, providing a new approach for the clinically accurate treatment of HCC.

Chitosan-coated liposomal systems for delivery of antibacterial peptide LL17-32 to Porphyromonas gingivalis

Periodontal disease is triggered by surface bacterial biofilms where bacteria are less susceptible to antibiotic treatment. The development of liposome-based delivery mechanisms for the therapeutic use of antimicrobial peptides is an attractive alternative in this regard. The cationic antimicrobial peptide LL-37 (human cathelicidin) is well-known to exert antibacterial activity against Porphyromonasgingivalis, a keystone oral pathogen. However, the antibacterial activity of the 16-amino acid fragment (LL17-32) of LL-37, is unknown. In addition, there are still gaps in studies using liposomal formulations as delivery vehicles of antibacterial peptides against this pathogen. This study was designed to examine the influence of the different types of liposomal formulations to associate and deliver LL17-32 to act against P. gingivalis. Chitosans of varying Mw and degree of acetylation (DA) were adsorbed at the surface of soya lecithin (SL) liposomes. Their bulk (average hydrodynamic size, ζ-potential and membrane fluidity) and ultrastructural (d-spacing, half-bilayer thickness and the water layer thickness) biophysical properties were investigated by a panel of techniques (DLS, SAXS, M3-PALS, fluorescence spectroscopy and TEM imaging). Their association efficiency, in vitro release, stability, and efficacy in killing the periodontal pathogen P. gingivalis were also investigated. All liposomal systems possessed spherical morphologies and good shelf-life stabilities. Under physiological conditions, chitosan formulations with a high DA demonstrated enhanced stability in comparison to low DA-chitosan formulations. Chitosans and LL17-32 both decreased SL-liposomal membrane fluidity. LL17-32 exhibited a high degree of association with SL-liposomes without in vitro release. In biological studies, free LL17-32 or chitosans alone, demonstrated microbicidal activity against P. gingivalis, however this was attenuated when LL17-32 was loaded onto the SL-liposome delivery system, presumably due to the restrained release of the peptide. A property that could be harnessed in future studies (e.g., oral mucoadhesive slow-release formulations).

Methotrexate-modified docetaxel liposome targeting with ginsenoside Rh2 as a membrane stabilizer for the treatment of ovarian cancer

At present, nano-agent-targeted therapy has become the main means of clinical treatment for ovarian cancer. Conventional liposomes, while commonly used as drug carriers, often suffer from stability issues that reduce drug bioavailability. Cholesterol, a frequent component in liposome membranes, may cause adverse effects such as dyspnea and shortness of breath when accumulated excessively. To address these challenges, we employed G-Rh2 as an alternative to cholesterol in liposome membranes as it acts as a membrane stabilizer to increase the stability of the liposome system. We prepared methotrexate-modified docetaxel liposomes (MTX@DTX-Rh2-Lips), characterized their properties and evaluated their stability. The ability of MTX@DTX-Rh2-Lips to target SKOV3 cells and loaded mice was confirmed. Assessments through CCK-8, EDU proliferation, and wound healing assay demonstrated the in vitro antitumor effects of MTX@DTX-Rh2-Lips. The in vivo antitumor effects of MTX@DTX-Rh2-Lips were evaluated by immunohistochemistry and immunofluorescence staining. Our findings revealed that MTX@DTX-Rh2-Lips was uniformly spherical and stable, effectively targeting the tumor site, inhibiting the proliferation, invasion, metastasis, and angiogenesis of SKOV3 cells, and affecting the expression of tumor-associated proteins, with a good safety profile. In conclusion, the successful establishment of MTX@DTX-Rh2-Lips introduces promising avenues for the clinical treatment of ovarian cancer.

Fine-tuning of liposome integrity for differentiated transcytosis and enhanced antitumor efficacy

Transcytosis-inducing nanomedicines have been developed to improve tumor extravasation. However, the fate during transcytosis across multicell layers and the structural integrity of the nanomedicines before reaching tumor cells could impact antitumor therapy. Here, a BAY 87–2243 (a hypoxia-inducible factor-1 inhibitor)-loaded liposomal system (HA-P-LBAY) modified by low molecular weight protamine (LMWP) and crosslinked by hyaluronic acid (HA) was constructed. This system could accomplish differentiate cellular transport in endothelial and tumor cells by fine-tuning its structural integrity, i.e. transcytosis across the endothelial cells while preserving structural integrity, facilitating subsequent retention and drug release within tumor cells via degradation-induced aggregation. In vitro cellular uptake and transwell studies demonstrated that HA-P-LBAY were internalized by endothelial cells (bEnd.3) via an active, caveolin and heparin sulfate proteoglycan (HSPG)-mediated endocytosis, and subsequently achieved transcytosis mainly through the ER/Golgi pathway. Moreover, the fluorescence resonance energy transfer (FRET) study showed that HA-crosslinking maintained higher integrity of HA-P-LBAY after transcytosis, more efficiently than electrostatic coating of HA (HA/P-LBAY). In addition, more HA-P-LBAY was retained in tumor cells (4T1) compared to HA/P-LBAY corresponding to its enhanced in vitro cytotoxicity. This may be attributed to better integrity of HA-P-LBAY post endothelial transcytosis and more degradation of HA in tumor cells, leading to more liposome aggregation and inhibition of their transcytosis, which was inferred by both TEM images and the HAase responsiveness assay proved by FRET. In vivo, HA-P-LBAY exhibited more potency in tumor suppression than the other formulations in both low and high permeability tumor models. This highlighted that fine-tuning of structural integrity of nanocarriers played a key role no matter whether the transcytosis of nanocarriers contributed to cellular transport. Collectively, this study provides a promising strategy for antitumor therapies by fine-tuning liposome integrity to achieve active trans-endothelial transport with structural integrity and selective aggregation for prolonged tumor retention.

Development and Characterization of Quercetin-Loaded Polymeric Liposomes with Gelatin-Poly(ethylene glycol)-Folic Acid Coating to Increase Their Long-Circulating and Anticancer Activity.

Liposomes as drug-delivery systems have been researched and applied in multiple scientific reports and introduced as patented products with interesting therapeutic properties. Despite various advantages, this drug carrier faces major difficulties in its innate stability, cancer cell specificity, and control over the release of hydrophobic drugs, particularly quercetin, a naturally derived drug that carries many desirable characteristics for anticancer treatment. To improve the effectiveness of liposomes to deliver quercetin by tackling and mitigating the mentioned hurdles, we developed a strategy to establish the ability to passively target cancerous cells, as well as to increase the bioavailability of loaded drugs by incorporating poly(ethylene glycol), gelatin, and folic acid moieties to modify the liposomal system's surface. This research developed a chemically synthesized gelatin, poly(ethylene glycol), and folic acid as a single polymer to coat drug-loaded liposome systems. Liposomes were coated with gelatin-poly(ethylene glycol)-folic acid by electrostatic interaction, characterized by their size, morphology, ζ potential, drug loading efficiency, infrared structures, differential scanning calorimetry spectra, and drug-releasing profiles, and then evaluated for their cytotoxicity to MCF-7 breast cancer cells, as well as cellular uptake, analyzed by confocal imaging to further elaborate on the in vitro behavior of the coated liposome. The results indicated an unusual change in size with increased coating materials, followed by increased colloidal stability, ζ potential, and improved cytotoxicity to cancer cells, as shown by the cellular viability test with MCF-7. Cellular uptake also confirmed these results, providing data for the effects of biopolymer coating, while confirming that folic acid can increase the uptake of liposome by cancer cells. In consideration of such results, the modified gelatin-poly(ethylene glycol)-folic acid-coated liposome can be a potential system in delivering the assigned anticancer compound. This modified biopolymer showed excellent properties as a coating material and should be considered for further practical applications in the future.

HER2-targeted, enzyme-activated liposomes show superior in vivo efficacy in an ovarian cancer model

Liposomes carrying chemotherapeutic drugs can accumulate passively in solid tumors at high levels. However, additional targeting of the liposomes towards e.g. receptors expressed on cancer cells may improve their interaction and therapeutic properties. In this study, we designed a liposomal delivery system, which utilizes the intrinsic characteristics of HER2-positive tumors to ensure efficient delivery of oxaliplatin to the cancer cells. On the liposome surface, trastuzumab, an antibody specific to the HER2 receptor, was shown to facilitate internalization by the cancer cells. A polyethylene glycol (PEG) layer on the liposome surface provides protection from mononuclear phagocyte system uptake. To optimize the interaction between liposomes and cancer cells, a protease-sensitive cleavable peptide linker was inserted at the base of each PEG. The PEG layer is then cleaved off by intra- and extracellular matrix metalloproteinases (MMPs) upon accumulation in the tumor. Our data demonstrate that the removal of PEG significantly destabilizes the liposomes and leads to substantial oxaliplatin release. The proposed beneficial effect of combining antibody-mediated internalization with MMP sensitivity was confirmed in a series of in vivo studies using ovarian cancer xenograft models. The results demonstrated that HER2-targeted MMP-sensitive liposomes have superior anticancer activity compared to non-targeted and non-cleavable liposomes.

Application of Nanotechnology for Herbal Medicine Development: A Review

Background: Herbal medicines have been extensively used to treat diseases since the prehistoric era, but written records date back more than 5,000 years only. All civilizations developed their knowledge of herbal medicines in a well-ordered system, such as Ayurveda, Unani, Traditional Chinese Medicine, etc. The interest in traditional medicine declined after the discovery of modern medicine. However, in the 21st century, herbal medicines are staging a comeback as the dangers and limitations of modern medicine have become more apparent and herbal medicines are viewed as a balanced and moderate approach to healing. Methods: This review includes the nanoformulations of phytoconstituents and extract. Advancements in analysis and clinical research prove the efficacy of nano-herbal medicines in preventing and treating diseases. This review is mostly about how nanotechnology can be used to help herbal medicines work better. Result: The major problems with herbal medicines are their poor solubility and stability. New technological advancements are capable of removing the problems associated with herbal medicine. Novel drug delivery systems such as microemulsion, liposome, niosome, and nano-drug delivery systems are used to enhance the safety and efficacy of herbal medicines. Conclusion: Nanotechnology has significant merit for herbal medicines, such as improving solubility, bioavailability, pharmacological activity enhancement, and stability enhancement.

Efficacy of a new system of targeted delivery of tenecteplase in acute myocardial infarction in an in vivo experiment

A new system of targeted delivery of tissue plasminogen activator tenecteplase for restoration of coronary blood flow in acute myocardial infarction in animal experiments was developed.The new system of targeted delivery of fibrinolytic consists of native (“free”) and encapsulated (“bound”) tenecteplase in liposomes, in the percentage ratio (60 and 40 %, respectively), which are conjugated through carboxylated dextran with fibrin-specific monoclonal antibodies Fnl-3C.The physicochemical characteristics of the obtained liposomes conjugated with fibrin-specific monoclonal antibodies (immunoliposomes) with tenecteplase were determined: immunoliposomes have a hydrodynamic diameter of ~76‒77 nm, a zeta potential of ~(‒33) mV, a polydispersity index of ~0.55. Modification of liposomes with fibrin-specific monoclonal antibodies does not alter thrombolytic activity.When using immunoliposomes the survival rate of animals with acute myocardial infarction is ~90 %, liposomal and native form of the drug ‒ 80 %.The use of immunoliposomal delivery system in animals with acute myocardial infarction leads to an increase in the free lumen of the infarct-related artery (p < 0.05) by 26 % compared to the liposomal delivery system and by 46 % compared to native tenecteplase. At the same time, the mass of ischemic myocardium on the background of thrombolytic therapy with>< 0.05) by 26 % compared to the liposomal delivery system and by 46 % compared to native tenecteplase. At the same time, the mass of ischemic myocardium on the background of thrombolytic therapy with immunoliposomes decreases (p < 0.05) by 16 % in rats in comparison with the liposomal system and by 26 % in comparison with native tenecteplase. The new system of targeted delivery of tenecteplase provides effective and safe thrombolysis in animal experiment> < 0.05) by 16 % in rats in comparison with the liposomal system and by 26 % in comparison with native tenecteplase.The new system of targeted delivery of tenecteplase provides effective and safe thrombolysis in animal experiment.

Synthetic Biomimetic Liposomes Harness Efferocytosis Machinery for Highly Efficient Macrophages-Targeted Drug Delivery to Alleviate Inflammation.

Macrophages play pivotal roles in the regulation of inflammatory responses and tissue repair, making them a prime target for inflammation alleviation. However, the accurate and efficient macrophages targeting is still a challenging task. Motivated by the efficient and specific removal of apoptotic cells by macrophages efferocytosis, a novel biomimetic liposomal system called Effero-RLP (Efferocytosis-mediated Red blood cell hybrid Liposomes) is developed which incorporates the membrane of apoptotic red blood cells (RBCs) with liposomes for the purpose of highly efficient macrophages targeting. Rosiglitazone (ROSI), a PPARγ agonist known to attenuate macrophage inflammatory responses, is encapsulated into Effero-RLP as model drug to regulate macrophage functions in DSS-induced colitis mouse model. Intriguingly, the Effero-RLP exhibits selective and efficient uptake by macrophages, which is significantly inhibited by the efferocytosis blocker Annexin V. In animal models, the Effero-RLP demonstrates rapid recognition by macrophages, leading to enhanced accumulation at inflammatory sites. Furthermore, ROSI-loaded Effero-RLP effectively alleviates inflammation and protects colon tissue from injury in the colitis mouse model, which is abolished by deletion of macrophages from mice model. In conclusion, the study highlights the potential of macrophage targeting using efferocytosis biomimetic liposomes. The development of Effero-RLP presents novel and promising strategies for alleviating inflammation.

Triplet-Triplet Annihilation Upconverting Liposomes: Mechanistic Insights into the Role of Membranes in Two-Dimensional TTA-UC.

Triplet-triplet annihilation upconversion (TTA-UC) implemented in nanoparticle assemblies is of emerging interest in biomedical applications, including in drug delivery and imaging. As it is a bimolecular process, ensuring sufficient mobility of the sensitizer and annihilator to facilitate effective collision in the nanoparticle is key. Liposomes can provide the benefits of two-dimensional confinement and condensed concentration of the sensitizer and annihilator along with superior fluidity compared to other nanoparticle assemblies. They are also biocompatible and widely applied across drug delivery modalities. However, there are relatively few liposomal TTA-UC systems reported to date, so systematic studies of the influence of the liposomal environment on TTA-UC are currently lacking. Here, we report the first example of a BODIPY-based sensitizer TTA-UC system within liposomes and use this system to study TTA-UC generation and compare the relative intensity of the anti-Stokes signal for this system as a function of liposome composition and membrane fluidity. We report for the first time on time-resolved spectroscopic studies of TTA-UC in membranes. Nanosecond transient absorption data reveal the BODIPY-perylene dyad sensitizer has a long triplet lifetime in liposome with contributions from three triplet excited states, whose lifetimes are reduced upon coinclusion of the annihilator due to triplet-triplet energy transfer, to a greater extent than in solution. This indicates triplet energy transfer between the sensitizer and the annihilator is enhanced in the membrane system. Molecular dynamics simulations of the sensitizer and annihilator TTA collision complex are modeled in the membrane and confirm the co-orientation of the pair within the membrane structure and that the persistence time of the bound complex exceeds the TTA kinetics. Modeling also reliably predicted the diffusion coefficient for the sensitizer which matches closely with the experimental values from fluorescence correlation spectroscopy. The relative intensity of the TTA-UC output across nine liposomal systems of different lipid compositions was explored to examine the influence of membrane viscosity on upconversion (UC). UC showed the highest relative intensity for the most fluidic membranes and the weakest intensity for highly viscous membrane compositions, including a phase separation membrane. Overall, our study reveals that the co-orientation of the UC pair within the membrane is crucial for effective TTA-UC within a biomembrane and that the intensity of the TTA-UC output can be tuned in liposomal nanoparticles by modifying the phase and fluidity of the liposome. These new insights will aid in the design of liposomal TTA-UC systems for biomedical applications.