Journal of Liposome Research最新文献

The clinical application of Isoquercitrin (IQ) is limited by its low water solubility and short retention time in the body, despite its diverse pharmacological effects. To address these issues, we prepared polyethylene glycol (PEG)-modified IQ liposomes (IQ-L) using the thin film dispersion method and optimized the formulation through a combination of One Factor at a Time (OFAT) method and response surface experiments. Characterization of the IQ-L that was prepared using the optimal formulation revealed a particle size of 185.48 nm, a polydispersity index of 0.252, a zeta potential of -33.88 mV, and an impressive encapsulation efficiency of 97.84%. In vitro release studies showed a significantly higher cumulative release rate for IQ-L compared to free IQ. Pharmacokinetic evaluations in rats demonstrated a 4.54-fold increase in the area under the concentration-time curve, a 1.63-fold prolongation of the half-life, and a 2.07-fold increase in peak concentration for IQ-L compared to unmodified IQ. Moreover, assessments of renal function in a mouse model indicated promising therapeutic effects. In summary, the PEG-modified liposome system greatly improved the solubility and in vivo retention time of IQ, thus making it a potential clinical agent for the treatment of chronic kidney disease (CKD).

Poorly water-soluble drugs are common and challenging in pharmaceutical industry. The poor solubility can reduce the drugs' therapeutic efficiency and bioavailability. Improving the solubility and bioavailability of poorly water-soluble drugs is a challenge and a main issue in the development and application of these drugs in pharmaceutical industry. Liposomes is phospholipid-based vesicular drug delivery system which act as drug carriers for both lipophilic or hydrophilic drugs and have the ability to solubilize the carried drugs. An innovative approach is the incorporation of cyclodextrins (CDs) into the liposomes encapsulating the drug molecules for improving safety and effectiveness of drug molecules by the use of water-soluble CDs properties, which allow the formation of CDs liposomes complexes with lipophilic molecules. CDs liposomes complex increases targeting effect, regulates drug release, improves drug properties and drug encapsulation efficiency. The aim of this review is to summarize the advantages and applications of liposomes incorporating CDs to enhance bioavailability of poorly soluble drugs.

We previously developed a modified ethanol injection (MEI) method to construct small interfering RNA (siRNA) lipoplexes by mixing a lipid-ethanol solution with an siRNA-containing phosphate-buffered saline solution. Here, we constructed siRNA lipoplexes with 11-((1,3-bis(dodecanoyloxy)-2-((dodecanoyloxy)methyl)propan-2-yl)amino)-N,N,N-trimethyl-11-oxoundecan-1-aminium bromide (TC-1-12), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, and poly(ethylene glycol) (PEG)-lipid using our MEI method. The siRNA lipoplexes were PEGylated with 1, 3, 5, and 10 mol% PEG cholesteryl ether (PEG-Chol), 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (mPEG-DMG), or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethylene glycol]) (mPEG-DSPE). PEGylation of siRNA lipoplexes with PEG-Chol did not attenuate the inhibitory effects of Luc and polo-like kinase 1 (PLK1) siRNA lipoplexes on the luciferase (Luc) activity and proliferation of human cervical carcinoma HeLa-Luc, human ovarian cancer SK-OV-3-Luc, and human breast cancer MCF-7-Luc cells stably expressing Luc. In contrast, PEGylated lipoplexes with 10 mol% mPEG-DMG inhibited Luc activity by Luc siRNA but considerably attenuated the PLK1 siRNA-mediated cytotoxic effects. For PEGylated siRNA lipoplexes with mPEG-DSPE, inhibitory effect of Luc siRNA on Luc activity decreased with increasing amounts of PEG modification, and PLK1 siRNA-mediated cytotoxic effects disappeared at more than 3 mol% PEGylation. Erythrocyte aggregation and hemolysis induction by the siRNA lipoplexes were effectively inhibited by 10 mol% PEGylation, irrespective of the PEG-lipid. Compared to those with 1 mol% PEG-Chol, PEGylated siRNA lipoplexes with 10 mol% PEG-Chol potently reduced siRNA accumulation in mouse lungs post-intravenous administration. Overall, TC-1-12-based siRNA lipoplexes with 10 mol% PEG-Chol exerted PLK1 siRNA-mediated cytotoxic effects, without inducing hemolysis and erythrocyte aggregation.

PEGylated liposomes play a critical role in drug delivery systems because they can evade immune recognition. However, conventional methods for synthesizing PEGylated liposomes often involve the direct incorporation of PEG-functionalized lipids, resulting in insufficient and inconsistent PEG distribution on the liposome surface, which compromises their stability and performance. In this study, we present a proof-of-concept synthesis approach that utilizes lipid-based initiators to form liposomes, followed by controllable grafting of PEG chains through atom transfer radical polymerization (ATRP). This method ensures controlled and uniform PEG coverage, resulting in improved functionality. Compared to conventional liposomes, the polymer-grafted liposomes synthesized via ATRP demonstrated superior cellular uptake in vitro, enhanced penetration of the blood-brain barrier (BBB), and improved stability in vivo, particularly for protein-encapsulated formulations such as green fluorescent protein (GFP). Live/dead assays confirmed the biocompatibility of the ATRP-synthesized PEGylated liposomes. Therefore, our strategy significantly enhances the efficiency of PEGylated liposomes for targeted brain drug delivery, providing a promising platform for the treatment of neurological disorders.

The synergistic approach of liposome integrated with gel matrix could reshape the current frameworks of drug delivery technology. The liposome-based approaches are limited by inadequate stability and rapid leakage of drug molecules. Undesired and immediate drug release from gel increases the local concentration of drug and causes toxicity. So, the stabilization of liposomes within a gel matrix can be an effective option to provide an ingenious solution to the conventional limitation on short half-life, instability, toxicity, uncontrolled drug release and poor retention of drug molecules on the target site. The capability to incorporate antibacterial as well as anti-oxidant drugs, antimicrobial peptides, ligands, growth hormones, antigens, and imaging agents had contributed to the establishment of multifunctional liposomal gel system has significant advantage in regenerative medicine area. This review will focus the advantage of multifunctional liposomal gels in context of infectious wound healing, skin rejuvenation, musculoskeletal repair and trauma management, spinal cord injury treatment, tumor specific chemotherapy as well as immunotherapy and vaccination. The versatility in executing the multiple functions will be a valuable solution for advancing the therapeutic outcomes in regenerative medicine.

Extrinsic skin aging is caused by chronic skin photodamage. The present study aims to inspect the role of nanoencapsulation of melatonin (MEL) in hyalurosomes in combating UVB-induced skin damage to take advantage of the hydrating penetration enhancing and antiaging effects of hyaluronic acid along with the powerful antioxidant effects of MEL. Measurement of particle size, zeta potential, encapsulation efficiency and in vitro MEL release were carried out. The in vivo photoprotective effects of MEL were tested in rats. A histopathological examination was conducted, and antioxidant and anti-inflammatory markers were measured along with estimating the expression of P38 MAPK, P-ERK and P-JNK. Particle size and zeta potential of MEL hyalurosomes were 285.9 nm and -26.3 mV with 95% entrapment efficiency and provided a sustained release profile for 48h. In vivo, results revealed the superior effect of MEL hyalurosomes in protecting skin against UVB-induced damage and reducing the levels of inflammatory mediators like TNF-α and IL6 compared with MEL suspension. However, they had a prominent role in increasing the levels of antioxidants. These findings may be accredited to the effect of nanoencapsulation in enhancing skin penetration and deposition of MEL besides the effect of hyaluronic acid as a powerful antiaging tool.

Here, we report a novel stimuli-responsive N-DOPE liposome where the redox-active 4-nitrobenzyl formate head group of liposomes would respond with respect to the presence of nitroreductase present in the environment of tumor tissues to release the payload. Our main emphasis is related to the construction of redox-sensitive liposomes that would function as the liposomal drug carriers to malignant tumors. Our N-DOPE liposome contains a nitro group (-NO₂) in the modified lipid, and we expect the reduction of the nitro group (-NO₂) to amine (-NH₂) would release the calcein (drug) through the 1,6 elimination as per our hypothesis. But we found no release after waiting for almost 20 hours with the use of Na₂S₂O₄, nitroreductase (NTR) and changes of different external environmental conditions, i.e. temperature, aerobic and anaerobic, etc. due to the formation of an azo (R-N = N-R) bond that stops the complete reduction of (-NO₂) all the way down to form amine (-NH₂) to stop releasing the payloads. However, adding an organic group containing nitro during the reduction process with the Na₂S₂O₄ resulted in a 45% release of liposomal content. A detailed study & explanation of the formation of azo bond in our N-DOPE liposome has been shown in a stepwise manner in through various spectroscopic methods, and we have discussed future directions.

Platelets, long recognized for their role in hemostasis and thrombosis, have emerged as key players in a wide array of physiological and pathological processes through the release of platelet-derived extracellular vesicles (PEVs). These nanoscale vesicles, rich in bioactive molecules such as proteins, lipids, and nucleic acids, facilitate intercellular communication and influence processes ranging from angiogenesis and inflammation to immune modulation and tissue repair. PEVs, the most abundant extracellular vesicles in circulation, display procoagulant activity 50-100 times greater than activated platelets, underscoring their pivotal role in hemostasis and thrombosis. Recent research has unveiled their dual role in health and disease, highlighting their potential as diagnostic biomarkers and therapeutic vehicles. PEVs are implicated in cancer progression, autoimmune diseases, and infectious diseases, where they modulate tumor microenvironments, immune responses, and inflammatory pathways. Moreover, their ability to deliver therapeutic agents with high specificity and biocompatibility positions them as promising tools in regenerative medicine, drug delivery, and targeted therapies. This review comprehensively explores PEV biogenesis, cargo composition, and their multifaceted roles in hemostasis and thrombosis, as well as their broader implications in disease. It also explores the potential of PEVs as diagnostic markers and innovative therapeutic strategies, offering insights into their application in treating thrombotic disorders, cancer, and inflammatory diseases. Despite significant advancements, challenges remain in standardizing isolation protocols and translating preclinical findings into clinical applications. Unlocking the full potential of PEVs promises to revolutionize diagnostics and therapeutics, paving the way for novel approaches to managing complex diseases.

Hyperlipidemia, a critical risk factor for various health conditions, necessitates innovative therapeutic strategies. Investigating the effectiveness of liposomal formulations in managing hyperlipidemia is essential. Resveratrol (RES)-loaded nanoliposomes present a promising new approach for hyperlipidemia treatment. In this study, we investigated the anti-hyperlipidemic potential of RES-loaded nanoliposomes in high-fat diet (HFD)-fed rats. The nanoliposomes were prepared using a thin-film hydration method. According to transmission electron microscopy (TEM) and dynamic light scattering (DLS) results, the mean size of prepared RES-loaded nanoliposomes were about 42 nm and 68 nm, respectively, with a zeta potential of -65.6 mV. The entrapment efficiency and loading content were 83.78% and 14.25%, respectively. Additionally, the RES-loaded nanoliposomes exhibited controlled release kinetics compared to the free RES form. Moreover, in a hyperlipidemic rat model induced by an HFD, orally administered RES-loaded nanoliposomes significantly reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG), while concurrently increasing high-density lipoprotein cholesterol (HDL-C) levels. Additionally, liver damage induced by HFD was alleviated by RES-loaded nanoliposomes. The expression levels of Toll-like receptor 3 (TLR3) and TIR domain-containing adaptor-inducing interferon-β (TRIF) were assessed using fluorescence immunohistochemistry. Notably, RES-loaded nanoliposomes significantly reduced the expression of these protein. The effect of RES-loaded nanoliposomes was measured on body weight of HFD rats, demonstrting RES-loaded nanoliposomes hold promise for weight management. These findings underscore the potential of RES-loaded nanoliposomes as a safe and effective therapeutic option for hyperlipidemia.