Conventional Liposomes Research Articles

Emerging Trends in Lipid-Based Vaccine Delivery: A Special Focus on Developmental Strategies, Fabrication Methods, and Applications

Lipid-based vaccine delivery systems such as the conventional liposomes, virosomes, bilosomes, vesosomes, pH-fusogenic liposomes, transferosomes, immuno-liposomes, ethosomes, and lipid nanoparticles have gained a remarkable interest in vaccine delivery due to their ability to render antigens in vesicular structures, that in turn prevents its enzymatic degradation in vivo. The particulate form of lipid-based nanocarriers confers immunostimulatory potential, making them ideal antigen carriers. Facilitation in the uptake of antigen-loaded nanocarriers, by the antigen-presenting cells and its subsequent presentation through the major histocompatibility complex molecules, leads to the activation of a cascade of immune responses. Further, such nanocarriers can be tailored to achieve the desired characteristics such as charge, size, size distribution, entrapment, and site-specificity through modifications in the composition of lipids and the selection of the appropriate method of preparation. This ultimately adds to its versatility as an effective vaccine delivery carrier. The current review focuses on the various lipid-based carriers that have been investigated to date as potential vaccine delivery systems, the factors that affect their efficacy, and their various methods of preparation. The emerging trends in lipid-based mRNA vaccines and lipid-based DNA vaccines have also been summarized.

Conventional and PEGylated Liposomes as Vehicles of Copaifera sabulicola

Traditional medicine uses resin oils extracted from plants of the genus Copaifera for several purposes. Resin oils are being studied to understand and profile their pharmacological properties. The aim of this work was to prepare and to characterize conventional and pegylated liposomes incorporating resin oils or the hexanic extract obtained from Copaifera sabulicola (copaiba) leaves. The cytotoxic effect of these products was also investigated. Conventional and stealth liposomes with copaiba extract showed similar average diameters (around 126 nm), encapsulation efficiencies greater than 75% and were stable for 90 days. A cytotoxicity test was performed on murine glioma cells and the developed liposomes presented antiproliferative action against these cancer cells at the average concentration of 30 μg/mL. Phytochemicals encapsulated in PEGylated liposomes induced greater reduction in the viability of tumor cells. In addition, bioassay-s measured the cytotoxicity of copaiba resin oil (Copaifera sabulicola) in liposomes (conventional and PEGylated), which was also checked against pheochromocytoma PC12 cells. Its safety was verified in normal rat astrocytes. The results indicate that liposomes encapsulating copaiba oil showed cytotoxic activity against the studied tumor strains in a dose-dependent fashion, demonstrating their potential applications as a chemotherapeutic bioactive formulation.

Evaluation of Conventional and Hyaluronic Acid-Coated Thymoquinone Liposomes in an In Vitro Model of Dry Eye.

Dry eye disease (DED) is a common ocular disorder characterized by an inadequate lubrication of the eye by tears leading to inflammation and the alteration of the ocular surface. Current treatments are often limited due to their side effects and ineffectiveness. Thymoquinone (TQ) is a natural compound present in the essential oil of Nigella sativa L., with anti-inflammatory and antioxidant activities. In this study, conventional and hyaluronic acid-coated liposomes were developed to improve TQ activity at ocular level. In the present study, the cytoprotective effects of TQ or TQ liposomes were assessed against oxidative and inflammatory processes in human corneal epithelial cells (HCE-2). Hyperosmolarity conditions (450 mOsm) were used as a model of DED. Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor (TNFα) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR); COX-2 and Phospho-NF-κB p65 (p-p65) by Western blotting (WB). Moreover, the mitochondrial reactive oxygen species (mtROS) levels were measured by MitoSOX assay. The hyperosmotic treatment induced a significant increase of the proinflammatory genes and proteins expression that were significantly decreased in the liposomes-treated cells. The coincubation with hyaluronic acid-coated liposomes significantly reverted the increase of mtROS production, evidently stimulated by the hyperosmotic stress. Our data suggest that TQ-loaded liposomes have potential as a therapeutic agent in dry eye disease, improving the TQ efficacy.

A “Trojan Horse” Strategy: The Preparation of Bile Acid-Modifying Irinotecan Hydrochloride Nanoliposomes for Liver-Targeted Anticancer Drug Delivery System Study

The bile acid transport system is a natural physiological cycling process between the liver and the small intestine, occurring approximately 6-15 times during the day. There are various bile acid transporter proteins on hepatocytes that specifically recognize bile acids for transport. Therefore, in this paper, a novel liposome, cholic acid-modified irinotecan hydrochloride liposomes (named CA-CPT-11-Lip), was prepared based on the "Trojan horse" strategy. The liposomes preparation process was optimized, and some important quality indicators were investigated. The distribution of irinotecan hydrochloride in mice was then analyzed by high-performance liquid chromatography (HPLC), and the toxicity of liposomes to hepatocellular carcinoma cells (HepG-2) was evaluated in vitro. As a result, CA-CPT-11-Lip was successfully prepared. It was spherical with a particle size of 154.16 ± 4.92 nm, and the drug loading and encapsulation efficiency were 3.72 ± 0.04% and 82.04 ± 1.38%, respectively. Compared with the conventional liposomes (without cholic acid modification, named CPT-11-Lip), CA-CPT-11-Lip had a smaller particle size and higher encapsulation efficiency, and the drug accumulation in the liver was more efficient, enhancing the anti-hepatocellular carcinoma activity of irinotecan hydrochloride. The novel nanoliposome modified by cholic acid may help to expand the application of irinotecan hydrochloride in the treatment of hepatocellular carcinoma and construct the drug delivery system mode of drug liver targeting.

Development of Spleen Targeting H2S Donor Loaded Liposome for the Effective Systemic Immunomodulation and Treatment of Inflammatory Bowel Disease.

Nanoparticles are primarily taken up by immune cells after systemic administration. Thus, they are considered an ideal drug delivery vehicle for immunomodulation. Because the spleen is the largest lymphatic organ and regulates the systemic immune system, there have been studies to develop spleen targeting nanoparticles for immunomodulation of cancer and immunological disorders. Inflammatory bowel disease (IBD) includes disorders involving chronic inflammation in the gastrointestinal tract and is considered incurable despite a variety of treatment options. Hydrogen sulfide (H2S) is one of the gasotransmitters that carries out anti-inflammatory functions and has shown promising immunomodulatory effects in various inflammatory diseases including IBD. Herein, we developed a delicately tuned H2S donor delivering liposome for spleen targeting (ST-H2S lipo) and studied its therapeutic effects in a dextran sulfate sodium (DSS) induced colitis model. We identified the ideal PEG type and ratio of liposome for a high stability, loading efficiency, and spleen targeting effect. In the treatment of the DSS-induced colitis model, we found that ST-H2S lipo and conventional long-circulating liposomes loaded with H2S donors (LC-H2S lipo) reduced the severity of colitis, whereas unloaded H2S donors did not. Furthermore, the therapeutic effect of ST-H2S lipo was superior to that of LC-H2S lipo due to its better systemic immunomodulatory effect than that of LC-H2S lipo. Our findings demonstrate that spleen targeting H2S lipo may have therapeutic potential for IBD.

Insights into Asymmetric Liposomes as a Potential Intervention for Drug Delivery Including Pulmonary Nanotherapeutics

Liposome-based drug delivery systems are nanosized spherical lipid bilayer carriers that can encapsulate a broad range of small drug molecules (hydrophilic and hydrophobic drugs) and large drug molecules (peptides, proteins, and nucleic acids). They have unique characteristics, such as a self-assembling bilayer vesicular structure. There are several FDA-approved liposomal-based medicines for treatment of cancer, bacterial, and viral infections. Most of the FDA-approved liposomal-based therapies are in the form of conventional "symmetric" liposomes and they are administered mainly by injection. Arikace® is the first and only FDA-approved liposomal-based inhalable therapy (amikacin liposome inhalation suspension) to treat only adults with difficult-to-treat Mycobacterium avium complex (MAC) lung disease as a combinational antibacterial treatment. To date, no "asymmetric liposomes" are yet to be approved, although asymmetric liposomes have many advantages due to the asymmetric distribution of lipids through the liposome's membrane (which is similar to the biological membranes). There are many challenges for the formulation and stability of asymmetric liposomes. This review will focus on asymmetric liposomes in contrast to conventional liposomes as a potential clinical intervention drug delivery system as well as the formulation techniques available for symmetric and asymmetric liposomes. The review aims to renew the research in liposomal nanovesicle delivery systems with particular emphasis on asymmetric liposomes as future potential carriers for enhancing drug delivery including pulmonary nanotherapeutics.

Design of Novel Tricaprylin-Incorporated Multi-Layered Liposomal System for Skin Delivery of Ascorbic Acid with Improved Chemical Stability.

L-ascorbic acid (Vit C) possesses a variety of dermatological functions in maintaining skin health and anti-aging properties. However, its topical application is challenging owing to its liability to light, oxygen, or heat. Therefore, in this study, a novel liposomal system, including a lipophilic neutral oil named a lipo-oil-some (LOS), was designed to improve the chemical stability and aid the skin absorption of Vit C. The vesicular systems were prepared using the ethanol injection method, employing phosphatidylcholine, cholesterol, dipalmitoyl-sn-glycerol-3-phosphoglycerol, and tricaprylin as neutral oil. The optimized LOS was characterized as follows: shape, multi-layered sphere; size, 981 nm; zeta potential, -58 mV; and Vit C encapsulation efficiency, 35%. The encapsulation of the labile compound into the novel system markedly enhanced photostability, providing over 10% higher Vit C remaining compared to Vit C solution or Vit C-loaded conventional liposome under a light intensity of 20,000 lx. On the other hand, the ex vivo skin permeation and accumulation of Vit C with the LOS system were comparable to those of smaller conventional liposomes (198 nm) in a Franz diffusion cell model mounted with porcine skin. Based on these findings, we concluded that the novel liposomal system could be utilized for skin delivery of Vit C with enhanced chemical stability.

Polysaccharide-modified liposomes and their application in cancer research.

Nanodrug delivery systems have been widely used in cancer treatment. Among these, liposomal drug carriers have gained considerable attention due to their biocompatibility, biodegradability, and low toxicity. However, conventional liposomes have several shortcomings, such as poor stability, rapid clearance, aggregation, fusion, degradation, hydrolysis, and oxidation of phospholipids. Polysaccharides are natural polymers of biological origin that exhibit structural stability, excellent biocompatibility and biodegradability, flexibility, non-immunogenicity, low toxicity, and targetability. Therefore, they represent a promising class of polymers for the modification of the surface properties of liposomes to overcome their shortcomings. In addition, polysaccharides can be readily combined with other materials to develop new composite materials. Hence, they represent the optimal choice for liposomal modification to improve pharmacokinetics and clinical utility. Polysaccharide-coated liposomes exhibit better stability, drug release kinetics, and cellular uptake than conventional liposomes. The oncologic application of polysaccharide-coated liposomes has become a research hotspot. We summarize the preparation, physicochemical properties, and antineoplastic effects of polysaccharide-coated liposomes to facilitate antitumor drug development.

Transfersome as Topical Drug Delivery: Formulation and Characterization

A transdermal delivery system is a non-invasive delivery system that provide a controlled therapeutic effect. However, this system has a barrier that is the outermost layer of the skin, so that only part of the drug can be administered via the transdermal route. The use of the vesicular system as a carrier for drugs or active substances is a solution for transdermal delivery systems to be able to pass through the skin barrier. One of the vesicular systems that can overcome this problem is transfersome. Displacement is elastic and can change shape by squeezing itself to pass through smaller-than-sized pores. In addition, transfersomes can encapsulate drugs or active substances that are amphiphilic, and have permeation ability than conventional liposomes. This review article aims to explain the definition and general description of transfersomes, their mechanism of action, methods of preparation and characterization, and their recent application in drug delivery using the vesicular transfersome system.

Enhanced skin penetration of Finasteride loaded DMSO-liposomes for the treatment of androgenic alopecia: comparison with conventional liposomes

Long-term treatment with finasteride (FIN) for androgenic alopecia is restricted due to its systemic side effects. To address this problem, DMSO-modified liposomes were prepared in the present study to improve the topical delivery of FIN. DMSO-liposomes were prepared by a modification of the ethanol injection method. It was hypothesized that the permeation-enhancing property of DMSO could promote drug delivery to deeper skin layer where hair follicles are present. Liposomes were optimized by quality by design (QbD) approach and biologically evaluated in a rat model of testosterone-induced alopecia. Optimized DMSO-liposomes were spherical and had mean vesicle size, zeta potential, and entrapment efficiency of 330.1 ± 1.5, −14.52 ± 1.32, and 59.02 ± 1.12%, respectively. Biological evaluation on testosterone-induced alopecia and skin histology shows that follicular density and anagen/telogen (A/T) ratio were increased in rats treated with DMSO-liposomes as compared to FIN-liposomes without DMSO and an alcoholic solution of FIN applied topically. DMSO-liposomes could be promising skin delivery vehicles for FIN or similar drugs.

Thermosensitive Liposomal Drug Delivery Systems: A Review

When combined with local hyperthermia or high intensity focused ultrasound, thermosensitive liposomes are a promising technique for externally directing medications to solid tumours. To selectively focus drug delivery to diseased or damaged tissue while reducing drug distribution to vital normal tissues is the main goal of liposomal drug delivery. An overview of temperature-sensitive liposomes is provided in this review. The ability to heat tumours with external energy sources in a controlled and predictable manner makes temperature-sensitive liposomes an especially alluring alternative. The lipids used to make conventional thermosensitive liposomes experience a gel-to-liquid phase shift many degrees above physiological temperature. Lysolipids and artificial temperature-sensitive polymers have recently been used to show how liposomes can be made to be sensitive to temperature. Thermosensitive liposomes (TSL) and localized hyperthermia are potent delivery vehicles for tumor-specific drugs. In addition to chemotherapy, hyperthermia is given to cancer patients to help certain chemotherapeutic medications work more effectively. Using temperature-sensitive liposomes in conjunction with localized hyperthermia, which specifically releases the medicine contained in the heated tumor tissue, can significantly increase the temperature-dependent effect.

Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes.

Chitosan-decorated liposomes were proposed for the first time for the intranasal delivery of acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) to the brain as a therapy for organophosphorus compounds (OPs) poisoning. Firstly, the chitosome composition based on phospholipids, cholesterol, chitosans (Cs) of different molecular weights, and its arginine derivative was developed and optimized. The use of the polymer modification led to an increase in the encapsulation efficiency toward rhodamine B (RhB; ~85%) and 2-PAM (~60%) by 20% compared to conventional liposomes. The formation of monodispersed and stable nanosized particles with a hydrodynamic diameter of up to 130 nm was shown using dynamic light scattering. The addition of the polymers recharged the liposome surface (from -15 mV to +20 mV), which demonstrates the successful deposition of Cs on the vesicles. In vitro spectrophotometric analysis showed a slow release of substrates (RhB and 2-PAM) from the nanocontainers, while the concentration and Cs type did not significantly affect the chitosome permeability. Flow cytometry and fluorescence microscopy qualitatively and quantitatively demonstrated the penetration of the developed chitosomes into normal Chang liver and M-HeLa cervical cancer cells. At the final stage, the ability of the formulated 2-PAM to reactivate brain AChE was assessed in a model of paraoxon-induced poisoning in an in vivo test. Intranasal administration of 2-PAM-containing chitosomes allows it to reach the degree of enzyme reactivation up to 35 ± 4%.

Multifunctional nanoparticles with anti-inflammatory effect for improving metabolic syndromes

Metabolic syndromes are a group of metabolic disorders for which the molecular mechanisms are still unclear. An increasing number of studies have implicated metabolic syndrome in the association with inflammation. Currently, lipsomes is known to improve nanoparticle hydrophobicity. Meanwhile, in drug delivery systems the application of cholesterol, which is commonly used to stabilise liposomal structures, has essentially no pharmacological effect on liposomes. Herein, we developed an ‘anti-inflammatory liposome’ (Phy-Lip) to effectively handle these challenges via employing Phytosterol instead of cholesterol. Different with the conventional liposomes, Phy-Lip is a much more brilliant nanoparticle with anti-inflammatory functions. In Phy-Lip, cholesterol was substituted by Phy, which works as membrane stabiliser, anti-inflammatory adjuvant at the same time. The experimental results show that Phy-Lip has a strong anti-inflammatory effect, and improves Metabolic syndromes. This study aims to provide a way to solve the challenge.

Design and applications of liposome-in-gel as carriers for cancer therapy

Cancer has long been a hot research topic, and recent years have witnessed the incidence of cancer trending toward younger individuals with great socioeconomic burden. Even with surgery, therapeutic agents serve as the mainstay to combat cancer in the clinic. Intensive research on nanomaterials can overcome the shortcomings of conventional drug delivery approaches, such as the lack of selectivity for targeted regions, poor stability against degradation, and uncontrolled drug release behavior. Over the years, different types of drug carriers have been developed for cancer therapy. One of these is liposome-in-gel (LP–Gel), which has combined the merits of both liposomes and hydrogels, and has emerged as a versatile carrier for cancer therapy. LP–Gel hybrids have addressed the lack of stability of conventional liposomes against pH and ionic strength while displaying higher efficiency of delivery hydrophilic drugs as compared to conventional gels. They can be classified into three types according to their assembled structure, are characterized by their nontoxicity, biodegradability, and flexibility for clinical use, and can be mainly categorized based on their controlled release, transmucosal delivery, and transdermal delivery properties for anticancer therapy. This review covers the recent progress on the applications of LP–Gel hybrids for anticancer therapy.

Updates on Responsive Drug Delivery Based on Liposome Vehicles for Cancer Treatment.

Liposomes are well-known nanoparticles with a non-toxic nature and the ability to incorporate both hydrophilic and hydrophobic drugs simultaneously. As modern drug delivery formulations are produced by emerging technologies, numerous advantages of liposomal drug delivery systems over conventional liposomes or free drug treatment of cancer have been reported. Recently, liposome nanocarriers have exhibited high drug loading capacity, drug protection, improved bioavailability, enhanced intercellular delivery, and better therapeutic effect because of resounding success in targeting delivery. The site targeting of smart responsive liposomes, achieved through changes in their physicochemical and morphological properties, allows for the controlled release of active compounds under certain endogenous or exogenous stimuli. In that way, the multifunctional and stimuli-responsive nanocarriers for the drug delivery of cancer therapeutics enhance the efficacy of treatment prevention and fighting over metastases, while limiting the systemic side effects on healthy tissues and organs. Since liposomes constitute promising nanocarriers for site-targeted and controlled anticancer drug release, this review focuses on the recent progress of smart liposome achievements for anticancer drug delivery applications.

High skin permeation, deposition and whitening activity achieved by xanthan gum string vitamin c flexible liposomes for external application

For most external applied antioxidant whitening ingredients, effective stratum corneum breakthrough, epidermal penetration and dermal deposition are necessary premises for inhibition of melanin production and transfer occurring in stratum basale. Herein, xanthan gum was added into vitamin C-containing flexible liposome (Vc-L) suspension. The long polymer chain of xanthan gum string dispersed Vc-L together to gain a lotion (Vc-LX) for external application. In this study, the storage stability experiments demonstrated that the additional xanthan gum could improve the storage stability of Vc liposome suspension. The cumulative in vitro skin penetration and deposition of Vc-LX was found to significantly increase within 24 h in mouse skin, compared with those of the Vc aqueous solution and Vc conventional liposomes treated groups (***p < 0.001). Most importantly, in vivo skin whitening experiments gave that Vc-LX has better skin whitening activity (ΔL*) than marketed products (GARNIER® Vc377), Vc flexible liposomes, and Vc conventional liposomes. Moreover, in vitro cytotoxicity experiments and skin irritation experiments demonstrated that Vc-LX has good biosafety. Therefore, this study suggested that Vc-LX may be a promising local skin delivery system for water-soluble antioxidant ingredients.

Highly Stable Liposomes Based on Tetraether Lipids as a Promising and Versatile Drug Delivery System.

Conventional liposomes often lack stability, limiting their applicability and usage apart from intravenous routes. Nevertheless, their advantages in drug encapsulation and physicochemical properties might be helpful in oral and pulmonary drug delivery. This study investigated the feasibility and stability of liposomes containing tetraether lipids (TEL) from Thermoplasma acidophilum. Liposomes composed of different molar ratios of TEL:Phospholipon 100H (Ph) were produced and exposed to various temperature and pH conditions. The effects on size, polydispersity index, and zeta potential were examined by dynamic and electrophoretic light scattering. Autoclaving, which was considered an additional process step after fabrication, could minimize contamination and prolong shelf life, and the stability after autoclaving was tested. Moreover, 5(6)-carboxyfluorescein leakage was measured after incubation in the presence of fetal calf serum (FCS) and lung surfactant (Alveofact). The incorporation of TEL into the liposomes significantly impacted the stability against low pH, higher temperatures, and even sterilization by autoclaving. The stability of liposomes containing TEL was confirmed by atomic force microscopy as images revealed similar sizes and morphology before and after incubation with FCS. It could be concluded that increasing the molar ratio in the TEL:Ph liposome formulations improved the structural stability against high temperature, low pH, sterilization via autoclaving, and the presence of FCS and lung surfactant.

Paclitaxel-loaded ginsenoside Rg3 liposomes for drug-resistant cancer therapy by dual targeting of the tumor microenvironment and cancer cells

IntroductionInherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various targeted drug-delivery systems, including nanoparticles and liposomes, are effective for MDR cancer treatment, their efficacy is restricted by immunosuppressive tumor microenvironment (TME). MethodsGinsenosides Rg3 was used to formulate unique Rg3-based liposomes loaded with PTX to establish Rg3-PTX-LPs, which were prepared by the thin-film hydration method. The stability of the Rg3-PTX-LPs was evaluated by particle size analysis through dynamic light scattering. The active targeting effect of Rg3-based liposomes was examined in an MCF-7/T xenograft model by an in a vivo imaging system. To evaluate the antitumor activity and mechanism of Rg3-PTX-LP, MTT, apoptosis assays, TAM regulation, and TME remodeling were performed in MCF-7/T cells in vitro and in vivo. ResultsRg3-PTX-LPs could specifically distribute to MCF7/T cancer cells and TME simultaneously, mainly through the recognition of GLUT-1. The drug resistance reversing capability and in vivo antitumor effect of Rg3-PTX-LPs were significantly improved compared with conventional cholesterol liposomes. The TME remodeling mechanisms of Rg3-PTX-LPs included inhibiting IL-6/STAT3/p-STAT3 pathway activation to repolarize protumor M2 macrophages to antitumor M1 phenotype, suppressing myeloid-derived suppressor cells (MDSCs), decreasing tumor-associated fibroblasts (TAFs) and collagen fibers in TME, and promoting apoptosis of tumor cells. Hence, through the dual effects of targeting tumor cells and TME remodeling, Rg3-PTX-LPs achieved a high tumor inhibition rate of 90.3%. ConclusionOur multifunctional Rg3-based liposome developed in the present study offered a promising strategy for rescuing the drug resistance tumor treatment.

Targeting therapy and tumor microenvironment remodeling of triple-negative breast cancer by ginsenoside Rg3 based liposomes

The chemotherapy effect of docetaxel (DTX) against triple-negative breast cancer (TNBC) remains mediocre and limited when encapsulated in conventional cholesterol liposomes, mainly ascribed to poor penetration and immunosuppressive tumor microenvironment (TME) caused by tumor stroma cells, especially cancer-associated fibroblasts (CAFs). Many studies have attempted to address these problems but trapped into the common dilemma of excessively complicated formulation strategies at the expense of druggability as well as clinical translational feasibility. To better address the discrepancy, ginsenoside Rg3 was utilized to substitute cholesterol to develop a multifunctional DTX-loaded Rg3 liposome (Rg3-Lp/DTX). The obtained Rg3-Lp/DTX was proved to be preferentially uptake by 4T1 cells and accumulate more at tumor site via the interaction between the glycosyl moiety of Rg3 exposed on liposome surface and glucose transporter1 (Glut1) overexpressed on tumor cells. After reaching tumor site, Rg3 was shown to reverse the activated CAFs to the resting stage and attenuate the dense stroma barrier by suppressing secretion of TGF-β from tumor cells and regulating TGF-β/Smad signaling. Therefore, reduced levels of CAFs and collagens were found in TME after incorporation of Rg3, inducing enhanced penetration of Rg3-Lp/DTX in the tumor and reversed immune system which can detect and neutralize tumor cells. Compared with wooden cholesterol liposomes, the smart and versatile Rg3-Lp/DTX could significantly improve the anti-tumor effect of DTX, providing a promising approach for TNBC therapy with excellent therapeutic efficacy and simple preparation process.

EthoLeciplex: a new tool for effective cutaneous delivery of minoxidil

This work designates EthoLeciplex, a vesicular system consisting of phospholipid, CTAB, ethanol and water, as an innovative vesicular system for cutaneous/transfollicular minoxidil (MX) delivery. MX-loaded EthoLeciplex was fabricated by one-step fabrication process. Formulations were designed to study the effects of drug/phospholipid ratio, CTAB/phospholipid ratio, and ethanol concentration on vesicular size, PDI, surface charge and EE%. The optimized formulation was characterized by in vitro release, drug/excipient compatibility, ex vivo skin permeability and safety. A size of 83.6 ± 7.3 to 530.3 ± 29.4 nm, PDI of 0.214 ± 0.01 to 0.542 ± 0.08 and zeta potential of +31.6 ± 4.8 to +57.4 ± 12.5 mV were observed. Encapsulation efficiency was obtained in its maximum value (91.9 ± 16.2%) at the lowest drug/phospholipid ratio, median CTAB/phospholipid and the highest ethanol concentration. The optimized formulation was consisted of 0.3 as drug/lipid ratio, 1.25 as CTAB/lipid ratio and 30% ethanol concentration and showed responses’ values in agreement with the predicted results. Differential scanning calorimetry studies suggested that EthoLeciplex existed in flexible state with complete incorporation of MX into lipid bilayer. The cumulative amount of MX permeated from EthoLeciplex, conventional liposome and ethanolic solution after 12 h were 36.3 ± 1.5 µg/ml, 21 ± 2.0 µg/ml and 55 ± 4.0 µg/ml respectively. Based on the remaining amount, the amount of MX accumulated in different skin layers can be predicted in descending order as follows; EthoLeciplex > conventional liposome > MX solution. EthoLeciplex produced marked disorder in the stratum corneum integrity and swelling with no features of skin toxicity. This new cationic system is a promising carrier for cutaneous/transfollicular drug delivery.