Development of techniques to produce nanoformulations in a controlled and reproducible manner is of great importance for research, clinical trials, and industrial scale-up. This research aimed to introduce a cost-effective micromixing approach for the nanoassembly of liposomes and compared with thin-film hydration (TFH) method. Numerical simulations and design of experiments (DOE) by response surface methodology (RSM) were used to evaluate the effects of input parameters on liposome properties, aiming to identify optimal conditions.
View Article and Find Full Text PDFObjectives: For safe and effective gene therapy, the ability to deliver the therapeutic nucleic acid to the target sites is crucial. In this study, lactosylated lipid phosphate calcium nanoparticles (lac-LCP) were developed for targeted delivery of pDNA to the hepatocyte cells. The lac-LCP formulation contained lactose-modified cholesterol (CHL), a ligand that binds to the asialoglycoprotein receptor (ASGR) expressed on hepatocytes, and polyethyleneimine (PEI) in the core.
View Article and Find Full Text PDFThe frequent administration rate required for Glatiramer acetate (GA), a first-line therapy for Multiple sclerosis (MS), poses patient compliance issues. Only a small portion of the subcutaneously administered GA is available for phagocytosis by macrophages, as most of it is hydrolyzed at its administration site or excreted renally. To unravel these hurdles, we have prepared liposomal formulations of GA through thin film-hydration method plus extrusion.
View Article and Find Full Text PDFPEGylation 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.
View Article and Find Full Text PDFIndoleamine-2,3-dioxygenase (IDO1) pathway has vital role in cancer immune escape and its upregulation leads to immunosuppressive environment which is associated with poor prognosis and progression in various cancers like melanoma. Previously, we showed the antitumoral efficacy of nanoliposomal form of Epacadostat (Lip-EPA), as an IDO1 inhibitor. Herein, we used Lip-EPA as a combination approach with liposomal gp100 (Lip-gp100) anti-cancer vaccine in melanoma model.
View Article and Find Full Text PDFBackground: Colorectal cancer is one of the prominent leading causes of fatality worldwide. Despite recent advancements within the field of cancer therapy, the cure rates and long-term survivals of patients suffering from colorectal cancer have changed little. The application of conventional chemotherapeutic agents like doxorubicin is limited by some drawbacks such as cardiotoxicity and hematotoxicity.
View Article and Find Full Text PDFCancer vaccine efficacy is limited by the immunosuppressive nature of the tumor microenvironment created by inflammation, immune inhibitory factors, and regulatory T cells (Tregs). Inspired by the role of cyclooxygenase-2 (COX-2) in inflammation in the tumor site, we proposed that normalization of the tumor microenvironment by celecoxib as a COX-2 inhibitor might improve the efficacy of Dendritic Cell (DC) therapy in a melanoma model. In the present study, liposomal celecoxib (Lip-CLX) was combined with ex vivo generated DC vaccines pulsed with gp100 peptide (in liposomal and non-liposomal forms) for prophylactic and therapeutic evaluation in the B16F10 melanoma model.
View Article and Find Full Text PDFSeveral obstacles limit the efficacy of brain tumour treatment, most notably the blood-brain barrier (BBB), which prevents the brain uptake of the majority of accessible medicines due to tight junctions. The presence of glutathione (GSH) receptors on the BBB surface has been demonstrated in numerous papers; consequently, products containing glutathione as a targeting ligand coupled with nanoliposomes are used to enhance drug delivery across the BBB. Here, the 5% pre-inserted PEG2000-GSH PEGylated liposomal doxorubicin was conducted according to 2B3-101 being tested in clinical trials.
View Article and Find Full Text PDFAtherosclerotic cardiovascular disease (ASCVD) is one of the major leading global causes of death. Genetic and epidemiological studies strongly support the causal association between triacylglycerol-rich lipoproteins (TAGRL) and atherogenesis, even in statin-treated patients. Recent genetic evidence has clarified that variants in several key genes implicated in TAGRL metabolism are strongly linked to the increased ASCVD risk.
View Article and Find Full Text PDFHesperidin and hesperetin are two important plant flavanones abundantly found in citrus fruit. They have discovered many biological activities to treat diseases, including cancer, diabetes, and Alzheimer's disease. Despite their various benefits, they have poor solubility, which reduces their bioavailability and absorption.
View Article and Find Full Text PDFIn this study redox-sensitive (RS) liposomes manufactured using 10,10'-diselanediylbis decanoic acid (DDA), an organoselenium RS compound, to enhance the therapeutic performance of doxorubicin (Dox). The DDA structure was confirmed by 1H NMR and LC-MS/MS. Various liposomal formulations (33 formulations) were prepared using DOPE, Egg PC, and DOPC with Tm ˂ 0 and DDA.
View Article and Find Full Text PDFTechnol Cancer Res Treat
May 2022
Our brain is protected by physio-biological barriers. The blood-brain barrier (BBB) main mechanism of protection relates to the abundance of tight junctions (TJs) and efflux pumps. Although BBB is crucial for healthy brain protection against toxins, it also leads to failure in a devastating disease like brain cancer.
View Article and Find Full Text PDFMultiple Sclerosis (MS) is an autoimmune disease with complicated immunopathology which necessitates considering multifactorial aspects for its management. Nano-sized pharmaceutical carriers named nanoparticles (NPs) can support impressive management of disease not only in early detection and prognosis level but also in a therapeutic manner. The most prominent initiator of MS is the domination of cellular immunity to humoral immunity and increment of inflammatory cytokines.
View Article and Find Full Text PDFExpert Opin Drug Deliv
December 2021
Introduction: Multiple Sclerosis (MS), as an autoimmune disease, has complicated immunopathology, which makes its management relevant to various factors. Novel pharmaceutical vehicles, especially liposomes, can support efficacious handling of this disease both in early detection and prognosis and also in a therapeutic manner. The most well-known triggers of MS onset are the predominance of cellular to humoral immunity and enhancement of inflammatory cytokines level.
View Article and Find Full Text PDFImmunotolerance induction in an antigen-specific manner is the long-term goal of immunotherapy to treat autoimmune diseases. Nanocarriers (NCs) can be designed as a new generation of delivery systems to modulate the immune responses through targeted delivery of antigens and immunomodulators to antigen presenting cells (APCs). In this manuscript, several formulation factors in the preparation of NCs which affect their uptake using APCs and generation of tolerance have been reviewed.
View Article and Find Full Text PDFThe drug delivery systems improve the efficacy of chemotherapeutics through enhanced targeting and controlled release however, biological barriers of tumor microenvironment greatly impede the penetration of nanomedicine within the tumor. We report herein the fabrication of a PEG-detachable silybin (SLB) pH-sensitive liposome decorated with TAT-peptide. For this, Acyl hydrazide-activated PEG was prepared and linked with ketone-derivatized DPPE via an acid-labile hydrazone bond to form mPEG-HZ-DPPE.
View Article and Find Full Text PDFLapatinib, a dual tyrosine kinase inhibitor, has poor water solubility, which results in poor and incomplete absorption from the gastrointestinal tract. To overcome this obstacle, we designed a stable and high-loaded liposomal formulation encapsulating lapatinib and examined its therapeutic efficacy in vitro and in vivo on TUBO and 4T1 cell lines. We also assessed the impact of liposomal lapatinib on the extent of the tumor and spleen-infiltrating lymphocytes and the autophagy and apoptosis gene expression within the tumor site.
View Article and Find Full Text PDFDendritic cell (DC) vaccination can be achieved via straight loading of vaccine into DCs ex vivo or administration to DCs in vivo. However, there is no certain consensus on which approach is preferable, and each strategy has its advantages and disadvantages, which affect the efficacy and safety of vaccines. It will also be more complicated when a vaccine delivery system is included.
View Article and Find Full Text PDFBackground: One of the important metabolic pathways in cancer progression is tryptophan catabolism by the indoleamin-2,3-dioxygenase (IDO) enzyme, which suppresses the immune system and induces tolerance. Inhibition of IDO1 is an important therapeutic goal for immunotherapy in many cancers such as metastatic melanoma. Epacadostat (EPA) is a very strong inhibitor of IDO1, and its clinical studies are being performed in a higher clinical phase than other inhibitors.
View Article and Find Full Text PDFLack of pre-existing tumor infiltrated T cells resulting in resistance to programmed cell death protein 1 (PD-1) blockade therapies can be solved by combining with anti-cancer vaccines and CpG-ODN in increasing T cell expansion and infiltration. Therefore, we prepared an ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of either liposomal or non-liposomal gp100 antigen (2.8 µg) plus CpG-ODN (800 ng) formulations and evaluated its anti-tumor activity in combination with anti-PD-1 therapy.
View Article and Find Full Text PDFObjectives: Whole lysate antigens (WLL) has been shown to be effective to tackle leishmaniasis in murine models. Although liposomes can be considered as promising vaccines, the activity of phospholipase-A (PLA) in WLL, breeds difficulties to preparing stable liposomal WLL. One strategy to overcome this shortcoming is to use lipids such as sphingomyelin (SM) which is resistant against PLA.
View Article and Find Full Text PDFThe aim of this study was to surface-functionalize PEGylated liposomal doxorubicin (PLD) using anti-p32 CGKRK peptide to evaluate its anti-angiogenic and anti-tumour activities. CGKRK was conjugated to DSPE-mPEG-maleimide and post-inserted into PLD at 25, 50, 100, 200 and 400 peptides per each liposome and characterised for their size, zeta potential, drug loading, release properties; and cell binding, cell uptake and cytotoxicity on three C26, 4T1 and human umbilical vein endothelial cell (HUVEC) cell lines. The results indicated the better efficiency of the PLD-100 (PLD with 100 CGKRK) formulation on 4T1 and HUVEC cell lines.
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