Journal of Liposome Research最新文献

This study aimed to formulate diacerein loaded terpene-enriched invasomes (DCN-TINV) to fulfill a fruitful management of osteoarthritis. A 2³ factorial design was adopted, including A: cholesterol concentration (%w/v), B: ethanol volume (mL) and C: phosphatidylcholine: drug ratio as the studied factors. Invasomes were constructed using the thin film hydration technique. Herein, percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI) and zeta potential (ZP) were statistically analyzed using Design-Expert^® software to select the optimum formula. The selected criteria for detecting the optimum formula were restricting PS (<350 nm), dismissing PDI, magnifying ZP (as absolute value) and EE%. The selected formula was further scrutinized through multiple in-vitro studies, including Fourier-transform infrared spectroscopy, differential scanning calorimetry, pH measurement, stability study, release profile and transmission electron microscopy. Furthermore, the ex-vivo performance was evaluated through ex-vivo skin permeation and deposition. Finally, it was subjected to an array of in-vivo tests, namely Draize test, histopathology, In-vivo skin penetration, edema size, and nociception inhibition measurements. The optimum formula with desirability (0.913) demonstrated EE% (89.21% ± 2.12%), PS (319.75 ± 10.11 nm), ZP (-55 ± 3.96 mV) and a prolonged release profile. Intriguingly, revamped skin permeation (1143 ± 32.11 µg/cm²), nociception inhibition (77%) and In-vivo skin penetration (144 µm) compared to DCN suspension (285 ± 21.25 µg/cm², 26% and 48 µm, respectively) were displayed. The optimum DCN-TINV exhibited plausible safety and stability profiles consolidated with auspicious efficacy for better management of osteoarthritis.

Diabetic wound is one of the most challenge in healthcare, requiring innovative approaches to promote efficient healing. In recent years, lipid nanoparticle-based drug delivery systems have emerged as a promising strategy for enhancing diabetic wound repair by stimulating angiogenesis. These nanoparticles offer unique advantages, including improved drug stability, targeted delivery, and controlled release, making them promising in enhancing the formation of new blood vessels. In this review, we summarize the emerging advances in the utilization of lipid nanoparticles to deliver angiogenic agents and promote angiogenesis in diabetic wounds. Furthermore, we provide an in-depth exploration of key aspects, including the intricate design and fabrication of lipid nanoparticles, their underlying mechanisms of action, and a comprehensive overview of preclinical studies. Moreover, we address crucial considerations pertaining to safety and the translation of these innovative systems into clinical practice. By synthesizing and analyzing the available knowledge, our review offers valuable insights into the future prospects and challenges associated with utilizing the potential of lipid nanoparticle-based drug delivery systems for promoting robust angiogenesis in the intricate process of diabetic wound healing.

PEGylation is a commonly used approach to prolong the blood circulation time of cationic liposomes. However, PEGylation is associated with the "PEG dilemma", which hinders binding and uptake into tumor cells. The cleavable PEG products are a possible solution to this problem. In the current research, doxorubicin-loaded cationic liposomes (Dox-CLs) surface-conjugated with a matrix metalloproteinase-2 (MMP-2)-sensitive octapeptide linker-PEG derivative were prepared and compared to non-PEGylated and PEGylated CLs in terms of size, surface charge, drug encapsulation and release, uptake, in vivo pharmacokinetics, and anticancer efficacy. It was postulated that PEG deshielding in response to the overexpressed MMP-2 in the tumor microenvironment increases the interaction of protected CLs with cellular membranes and improves their uptake by tumor cells/vasculature. MMP2-responsive Dox-CLs had particle sizes of ∼115-140 nm, surface charges of ∼+25 mV, and encapsulation efficiencies of ∼85-95%. In vitro cytotoxicity assessments showed significantly enhanced uptake and cytotoxicity of PEG-cleavable CLs compared to their non-cleavable PEG-coated counterparts or Caelyx^®. Also, the chick chorioallantoic membrane assay showed great antiangiogenesis ability of Dox-CLs leading to target and prevent tumor neovascularization. Besides, in vivo studies showed an effective therapeutic efficacy of PEG-cleavable Dox-CLs in murine colorectal cancer with negligible hematological and histopathological toxicity. Altogether, our results showed that MMP2-responsive Dox-CLs could be served as a promising approach to improve tumor drug delivery and uptake.

The object of the current study was to develop and evaluate trastuzumab-conjugated Paclitaxel (PTX) and Elacridar (ELA)-loaded PEGylated pH-sensitive liposomes (TPPLs) for site-specific delivery of an anticancer drug. In this study, paclitaxel is used as an anticancer drug which promotes microtubules polymerization and arrest cell cycle progression at mitosis and subsequently leading to cell death. The single use of PTX causes multiple drug resistance (MDR) and results failure of the therapy. Hence, the combination of PTX and P-glycoprotein inhibitor (ELA) are used to achieve maximum therapeutic effects of PTX. Moreover, monoclonal antibody (trastuzumab) is used as ligand for the targeting the drug bearing carriers to BC. Thus, trastuzumab anchored pH-sensitive liposomes bearing PTX and ELA were developed using thin film hydration method and Box-Behnken Design (BBD) for optimizing various formulation variables. The optimized liposomes undergo characterization such as vesicle size, PDI, and zeta potential, which were observed to be 122 ± 2.14 nm, 0.224, and -15.5 mV for PEGylated pH-sensitive liposomes (PEG-Ls) and 134 ± 1.88 nm, 0.238, and -13.98 mV for TPPLs, respectively. The results of the in vitro drug release study of both formulations (PEG-Ls and TPPLs) showed enhanced percentage drug release at an acidic pH 5 as compared to drug release at a physiological pH 7.4. Further, the in vitro cytotoxicity studies were performed in the SK-BR-3 and MDA-MB-231 cell lines. The cellular uptake study of FITC-loaded TPPLs in SK-BR-3 cells showed greater uptake than FITC-loaded PEG-Ls, while in MDA-MB-231 cells there was no significant difference in cell uptake between FITC-loaded TPPLs and FITC-loaded PEG-Ls. Hence, it can be concluded that the HER-2 overexpressing cancer cell line (SK-BR-3) was showed better cytotoxicity and cell uptake of TPPLs than the cells that expressed low levels of HER2 (MDA-MB-231). The in vivo tumor regression study, TPPLs showed significantly more tumor burden reduction i.e. up ∼74% as compared to other liposomes after 28 days. Furthermore, the in vivo studies of TPPLs showed a minimal toxicity profile, minimal hemolysis, higher tumor tissue distribution, and superior antitumor efficacy as compared to other formulations. These studies confirmed that TPPLs are a safe and efficacious treatment for breast cancer.

Solid Lipid Nanoparticles (SLN), the first type of lipid-based solid carrier systems in the nanometer range, were introduced as a replacement for liposomes. SLN are aqueous colloidal dispersions with solid biodegradable lipids as their matrix. SLN is produced using processes like solvent diffusion method and high-pressure homogenization, among others. Major benefits include regulated release, increased bioavailability, preservation of peptides and chemically labile compounds like retinol against degradation, cost-effective excipients, better drug integration, and a broad range of applications. Solid lipid nanoparticles can be administered via different routes, such as oral, parenteral, pulmonary, etc. SLN can be prepared by using high shear mixing as well as low shear mixing. The next generation of solid lipids, nanostructured lipid carriers (NLC), can reduce some of the drawbacks of SLN, such as its restricted capacity for drug loading and drug expulsion during storage. NLC are controlled nanostructured lipid particles that enhance drug loading. This review covers a brief introduction of solid lipid nanoparticles, manufacturing techniques, benefits, limitations, and their characterization tests.

Nano-drug delivery systems have opened new pathways for tumor treatment by overcoming some of the limitations of conventional drugs, such as physiological degradation, short half-life, and rapid release. Liposomes are promising nanocarrier systems due to their biocompatibility, low toxicity, and high inclusivity, as well as their enhanced drug bioavailability. Various strategies for active targeting of liposomal formulations have been investigated to achieve the highest drug efficacy. This review aims to summarize current developments in novel liposomal formulations, particularly ligand-targeted liposomes (such as folate, transferrin, hyaluronic acid, antibodies, aptamer, and peptide, etc.) used for the therapy of various cancers and provide an insight on the challenges and future of liposomes for scientists and pharmaceutical companies.

Thermoresponsive drug delivery systems have been used to treat diseases that cause hyperthermia or elevated body tissue temperatures, viz., rheumatoid arthritis and different cancers. The aim of the study was to enhance berberine (BER) release using thermosensitive nanostructured lipid carriers (TNLCs) through intra-articular administration for the management of arthritis. TNLCs were prepared using binary mixtures of stearic acid and decanoic acid as solid and liquid lipids, respectively. Lipid mixtures with an optimum melting point were assessed using differential scanning calorimetry studies. In vitro characterization of the BER TNLCs included particle size, zeta potential, entrapment efficiency, and drug release at 37 °C and 41 °C. Joint diameter measurement, real-time polymerase chain reaction (RT-PC) analysis, enzyme-linked immunosorbent assay (ELISA) for inflammatory markers, and histological evaluation of the dissected joints were all performed in vivo on rats with adjuvant-induced arthritis. In vitro characterization revealed negatively charged BER-loaded TNLCs with a spherical shape, particle size less than 500 nm, BER entrapment efficiency up to 79%, and a high drug release rate at an elevated temperature of 41 °C. In silico studies revealed the affinity of BER to different formula components and to the measured biomarkers. In vivo assessment of the optimum TNLCs showed that BER TNLCs were superior to the BER solution suspension regarding their effect on inflammatory biomarkers, joint diameter, and histological studies.

Glioma is one of the most severe central nervous systems (CNS)-specific tumors, with rapidly growing malignant glial cells accounting for roughly half of all brain tumors and having a poor survival rate ranging from 12 to 15 months. Despite being the most often used technique for glioma therapy, conventional chemotherapy suffers from low permeability of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) to anticancer drugs. When it comes to nanocarriers, liposomes are thought of as one of the most promising nanocarrier systems for glioma treatment. However, owing to BBB tight junctions, non-targeted liposomes, which passively accumulate in most cancer cells primarily via the increased permeability and retention effect (EPR), would not be suitable for glioma treatment. The surface modification of liposomes with various active targeting ligands has shown encouraging outcomes in the recent times by allowing various chemotherapy drugs to pass across the BBB and BBTB and enter glioma cells. This review article introduces by briefly outlining the landscape of glioma, its classification, and some of the pathogenic causes. Further, it discusses major barriers for delivering drugs to glioma such as the BBB, BBTB, and tumor microenvironment. It further discusses modified liposomes such as long-acting circulating liposomes, actively targeted liposomes, stimuli responsive liposomes. Finally, it highlighted the limitations of liposomes in the treatment of glioma and the various actively targeted liposomes undergoing clinical trials for the treatment of glioma.

Psoriasis is a chronic, immune-mediated skin disease with no cure. Intravenous arsenic trioxide (ATO) has been used to treat psoriasis in animal studies. However, the high toxicity of ATO limits its application to clinics for systemic administration. The aim of this study was to fabricate sustained-release ATO liposome gels (ATO-Lip-Gels) to be used for the treatment of psoriasis. The ATO Liposomes were prepared using a zinc acetate gradient method. ATO concentrations were analyzed by HPLC-HG-AFS. The ATO-Lip-Gels were characterized with respect to size, zeta potential, and entrapment efficiency. Stability, in vitro drug release, and in vivo efficacy were also evaluated. The optimal formulation of ATO-Lip was ATO (0.45%), S100 (9%), and cholesterol (1.5%) (W/V) in 0.3 mol/L zinc acetate and incubated for 10 min. In the in vitro drug release study, ATO-Lip-Gels exhibited a slower release profile of ATO than that from Gels only. Compared with the model group, ATO-Lip-Gels-H significantly reduced PASI scores after psoriasis in mice and was superior to tacrolimus at day 5. HE staining showed that the pathological changes caused by psoriasis in mice were significantly improved in the treatment groups, and ATO-Lip-Gels-H had the best effect among the treatment groups. ATO-Lip-Gels applied topologically to imiquimote-induced psoriatic plaque models significantly reduced the levels of key psoriatic cytokines such as IL-6 and TNF-α. We have developed ATO-Lip-Gels for the treatment of psoriasis, which demonstrated higher efficacy with the benchmark, Tacrolimus, and can be an alternative to the conventional treatment with Tacrolimus.

Curable approaches for primary osteosarcoma are inadequate and urge investigation of novel therapeutic formulations. Cannabinoid ligands exert antiproliferative and apoptotic effect on osteosarcoma cells via cannabinoid 2 (CB2) or transient receptor potential vanilloid type (TRPV1) receptors. In this study, we confirmed CB2 receptor expression in MG63 and Saos-2 osteosarcoma cells by qRT-PCR and flow cytometry (FCM), then reported the reduction effect of synthetic specific CB2 receptor agonist CB65 on the proliferation of osteosarcoma cells by WST-1 (water-soluble tetrazolium-1) and RTCA (real-time impedance-based proliferation). CB65 revealed an IC50 (inhibitory concentration) for MG63 and Saos-2 cells as 1.11 × 10^-11 and 4.95 × 10^-11 M, respectively. The specific antiproliferative effect of CB65 on osteosarcoma cells was inhibited by CB2 antagonist AM630. CB65 induced late apoptosis of MG63 and Saos-2 cells at 24 and 48 h, respectively by FCM when applied submaximal concentration. A novel CB65 liposomal system was generated by a thin film hydration method with optimal particle size (141.7 ± 0.6 nm), polydispersity index (0.451 ± 0.026), and zeta potential (-10.9 ± 0.3 mV) values. The encapsulation efficiency (EE%) of the CB65-loaded liposomal formulation was 51.12%. The CB65 and CB65-loaded liposomal formulation releasing IC50 of CB65 reduced proliferation by RTCA and invasion by scratch assay and induced late apoptosis of MG63 and Saos-2 cells, by FCM. Our results demonstrate the CB2 receptor-mediated antiproliferative and apoptotic effect of a new liposomal CB65 delivery system on osteosarcoma cells that can be used as a targeted and intelligent tool for bone tumors to ameliorate pediatric bone cancers following in vivo validation.