Herein, we report ethosome (ET) formulations composed of a safe amount of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC)-based ionic liquid with various concentrations of ethanol as a carrier for the transdermal delivery of a high molecular weight drug, insulin. The Insulin-loaded ET vesicles exhibited long-term stability compared to conventional DMPC ETs, showing significantly higher drug encapsulation efficiency and increased skin permeation ability.
Cardiovascular diseases are caused by hypercholesterolemia. Astaxanthin (AST) has been reported to exhibit antioxidant and anti-inflammatory properties. However, its bioavailability is poor because of low solubility and instability. In order to improve the bioavailability of AST, we developed an intestinal-responsive composite carrier termed as "liposomes in micropheres" incorporating N-succinyl-chitosan (NSC)-poly(ethylene glycol) (PEG) liposomes that functionalized by neonatal Fc receptors (FcRn) into hydrogels of sodium alginate (SA) and carboxymethyl chitosan (CMCS). In the AST NSC/HSA-PEG liposomes@SA/CMCS microspheres, the AST's encapsulation efficiency (EE) was 96.26% (w/w) and its loading capacity (LC) was 6.47% (w/w). AST NSC/HSA-PEG liposomes had stability in the gastric conditions and achieved long-term release of AST in intestinal conditions. Then, AST NSC/HSA-PEG liposomes@SA/CMCS bind to intestinal epithelial cell targets by the neonatal Fc receptor. In vitro permeation studies show that there was a 4-fold increase of AST NSC/HSA-PEG liposomes@SA/CMCS in AST permeation across the intestinal epithelium. Subsequent in vivo experiments demonstrated that the composite carrier exhibited a remarkable mucoadhesive capacity, allowing for extended intestinal retention of up to 12 h, and it displayed deep penetration through the mucus layer, efficiently entering the intestinal villi epithelial cells, and enhancing the absorption of AST and its bioavailability in vivo. And oral administration of AST NSC/HSA-PEG liposomes@SA/CMCS could effectively prevent hypercholesterolemia caused by a high-fat, high-cholesterol diet (HFHCD). These advancements highlight the potential of NSC/HSA-PEG liposomes@SA/CMCS composite carriers for targeted and oral uptake of hydrophobic bioactives.
Colorectal cancer (CRC) continues to be one of the most prevalent and deadliest forms of cancer worldwide, despite notable advancements in its management. The prognosis for metastatic CRC remains discouraging, with a relative 5-year survival rate for stage IV CRC patients. Conventional treatments for advanced malignancies such as chemotherapy, often face limitations in effectively targeting cancer cells resulting in off-target distribution and significant side effects. In the quest for better strategies, researchers have explored numerous alternatives. Among these, nanoparticles (NPs) specifically liposomes have emerged as one of the most promising candidates in developing targeted delivery systems for cancer therapeutics. This review discusses the current approaches employing functionalised liposomes to overcome major biological barriers in therapeutics delivery for CRC treatment. We have also shared our perspectives on the technological development of liposomes for future clinical use and highlighted a few useful insights on the material choices for future research work in CRC.
Extracellular vesicles (EVs) are small vesicles that are naturally released by cells and play a crucial role in cell-to-cell communication, tissue repair and regeneration. As naturally secreted EVs are limited, liposomes with different physicochemical properties, such as 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and linoleic acid (LA) with modifications have been formulated to improve EVs secretion for in vitro wound healing. Various analyses, including dynamic light scattering (DLS) and transmission electron microscopy (TEM) were performed to monitor the successful preparation of different types of liposomes. The results showed that cholesterol-LA liposomes significantly improved the secretion of EVs from immortalized adipose-derived mesenchymal stem cells (AD-MSCs) by 1.5-fold. Based on the cell migration effects obtained from scratch assay, both LA liposomal-induced EVs and cholesterol-LA liposomal-induced EVs significantly enhanced the migration of human keratinocytes (HaCaT) cell line. These findings suggested that LA and cholesterol-LA liposomes that enhance EVs secretion are potentially useful and can be extended for various tissue regeneration applications.
Drug delivery through the skin improves solubility, bioavailability, and unwanted systemic side effects of the drug. The selection of a suitable carrier is a challenging process. The conventional lipid vesicles have some limitations. They deliver the drug in the stratum corneum and have poor colloidal stability. Here comes the need for ultra-deformable lipid vesicles to provide the drug beyond the stratum corneum. Transethosomes are novel ultra-deformable vesicles that can deliver drugs into deeper tissues. The composition of transethosomes includes phospholipid, ethanol and surfactants. Each ingredient has a pivotal role in the properties of the carrier. This review covers the design, preparation method, characterisation, and characteristics of the novel vesicle. Also, we cover the impact of surfactants on vesicular properties and the skin permeation behaviour of novel vesicles.
The central dogma of molecular biology was no longer "central" after ground-breaking discoveries conveyed gene expression involves more complex physiological functions in cancer pathogenesis over the last decade. MicroRNAs (miRNAs) are short non-coding RNA that regulate gene expression, affecting key molecular pathways involved in sustaining the proliferative signalling for tumour development, evasion of cellular death, invasion, angiogenesis, as well as metastasis in a plethora of cancer types. MiRNA expression is dysregulated in human cancer through a number of processes, including miRNA gene amplification or deletion, faulty miRNA transcriptional regulation, dysregulated epigenetic alterations, and flaws in the miRNA biogenesis machinery. As a result, the current progress of treatment intervention focuses on modifying the miRNA levels in cancer therapeutics. Nevertheless, the mode of delivery and current management of miRNA therapies remains one of the many questions that need to be addressed. Here, we provided a comprehensive mini-review outlining the role of miRNA in cancer as well as its mode of delivery which includes liposomes, viral vectors, inorganic material-based nanoparticles, and cell-derived membrane vesicles. Likewise, the regulation of miRNA in other diseases and their challenges in translational research was also thoroughly discussed.
Current anticancer drug research includes tumor-targeted administration as a critical component because it is the best strategy to boost efficacy and decrease toxicity. Low drug concentration in cancer cells, nonspecific distribution, rapid clearance, multiple drug resistance, severe side effects, and other factors contribute to the disappointing results of traditional chemotherapy. As an innovative technique of treatments for hepatocellular carcinoma (HCC) in recent years, nanocarrier-mediated targeted drug delivery systems can overcome the aforesaid limitations via enhanced permeability and retention effect (EPR) and active targeting. Epidermal growth factor receptor (EGFR) inhibitor Gefitinib (Gefi) has dramatic effects on hepatocellular carcinoma. Herein, we developed and assessed an αvβ3 integrin receptor targeted c(RGDfK) surface modified liposomes for better targeting selectivity and therapeutic efficacy of Gefi on HCC cells. The conventional and modified Gefi loaded liposomes, i.e., denoted as Gefi-L and Gefi-c(RGDfK)-L, respectively, were prepared through the ethanol injection method and optimized via Box Behnken design (BBD). The FTIR and 1H NMR spectroscopy verified that the c(RGDfK) pentapeptides had formed an amide bond with the liposome surface. In addition, the particle size, Polydispersity index, zeta potential, encapsulation efficiency, and in-vitro Gefi release of the Gefi-L and Gefi-c(RGDfK)-L were measured and analyzed. As indicated by the MTT assay on HepG2 cells, Gefi-c(RGDfK)-L displayed considerably higher cytotoxicity than Gefi-L or Gefi alone. Throughout the incubation period, HepG2 cells took up significantly more Gefi-c(RGDfK)-L than Gefi-L. According to the in vivo biodistribution analysis, Gefi-c(RGDfK)-L accumulated more strongly at the tumor site than Gefi-L and free Gefi. Furthermore, HCC-bearing rats treated with Gefi-c(RGDfK)-L showed a substantial drop in liver marker enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, and total bilirubin levels) compared to the disease control group. Gefi-c(RGDfK)-L suppresses tumour growth more effectively than Gefi-L and free Gefi, according to an in vivo analysis of their anticancer activities. Thus, c(RGDfK)-surface modified liposomes, i.e., Gefi-c(RGDfK)-L may serve as an efficient carrier for the targeted delivery of anticancer drugs.
The future of molecular-level therapy, efficient medical diagnosis, and drug delivery relies on the effective theragnostic function which can be achieved by the synergistic effect of fluorescent carbon dots (FCDs) liposomes (L) and nanoliposomes. FCDs act as the excipient navigation agent while liposomes play the role of the problem-solving agent, thus the term "theragnostic" would describe the effect of LFCDs properly. Liposomes and FCDs share some excellent at-tributes such as being nontoxic and biodegradable and they can represent a potent delivery system for pharmaceutical compounds. They enhance the therapeutic efficacy of drugs via stabilizing the encapsulated material by circumventing barriers to cellular and tissue uptake. These agents facilitate long-term drug biodistribution to the intended locations of action while eliminating systemic side effects. This manuscript reviews recent progress with liposomes, nanoliposomes (collectively known as lipid vesicles) and fluorescent carbon dots, by exploring their key characteristics, applications, characterization, performance, and challenges. An extensive and intensive understanding of the synergistic interaction between liposomes and FCDs sets out a new research pathway to an efficient and theragnostic / theranostic drug delivery and targeting diseases such as cancer.
Breast cancer (BC) is among the most frequent malignancies women face around the globe. Nanotherapeutics are constantly evolving to overcome the limitations of conventional diagnostic and therapeutic approaches. Nanotechnology-based nanocarriers have a higher entrapment efficiency, low cytotoxicity, greater stability and improved half-life than conventional therapy. Nano-drug delivery systems have improved pharmacokinetics and pharmacodynamics parameters because of nanomeric size. Currently, various nano-formulations are in preclinical and clinical settings for breast cancer, like polymeric nanoparticles, micelles, nanobodies, magnetic nanoparticles, liposomes, niosomes, gold-nanoparticles, dendrimers and carbon-nanotubes. This review highlights the recent advancement in developing nano-drug delivery systems for BC treatment. This review will open the gateway to researchers to understand the current approaches to developing nano-formulation and improving problems associated with conventional therapy.
The unprecedented outbreak of severe acute respiratory syndrome-2 (SARS-CoV-2) worldwide has rendered it one of the most notorious pandemics ever documented in human history. As of November 2022, nearly 626 million cases of infection and over 6.6 million deaths have been reported globally. The scientific community has made significant progress in therapeutics and prevention for the management of coronavirus disease (COVID-19), including the development of vaccines and antiviral agents such as monoclonal antibodies and antiviral drugs. Although many advancements and a plethora of positive results have been obtained and global restrictions are being uplifted, obstacles in efficiently delivering these therapies, such as their rapid clearance, suboptimal biodistribution, and toxicity to organs, have yet to be addressed. To address these drawbacks, researchers have attempted applying nanotechnology-based formulations. Here, we summarized the recent data about COVID-19, its emergence, pathophysiology and life cycle, diagnosis, and currently-available medications. Subsequently, we discussed the progress in lipid nanocarriers, such as liposomes in infection detection and control. This review provides critical insights into the design of the latest liposomal-based formulations for tackling the barriers to detecting, preventing, and treating SARS-CoV-2.
The site-specific delivery of antitumor agents is of importance for providing effective cancer suppression. Poor bioavailability of anticancer compounds and the presence of biological barriers prevent their accumulation in tumor sites. These obstacles can be overcome using liposomal nanostructures. The challenges in cancer chemotherapy and stimuli-responsive nanocarriers are first described in the current review. Then, stimuli-responsive liposomes including pH-, redox-, enzyme-, light-, thermo- and magneto-sensitive nanoparticles are discussed and their potential for delivery of anticancer drugs is emphasized. The pH- or redox-sensitive liposomes are based on internal stimulus and release drug in response to a mildly acidic pH and GSH, respectively. The pH-sensitive liposomes can mediate endosomal escape via proton sponge. The multifunctional liposomes responsive to both redox and pH have more capacity in drug release at tumor site compared to pH- or redox-sensitive alone. The magnetic field and NIR irradiation can be exploited for external stimulation of liposomes. The light-responsive liposomes release drugs when they are exposed to irradiation; thermosensitive-liposomes release drugs at a temperature of >40 °C when there is hyperthermia; magneto-responsive liposomes release drugs in presence of magnetic field. These smart nanoliposomes also mediate co-delivery of drugs and genes in synergistic cancer therapy. Due to lack of long-term toxicity of liposomes, they can be utilized in near future for treatment of cancer patients.
Flavonoids represent a major group of polyphenolic compounds. Their capacity to inhibit tumor proliferation, cell cycle, angiogenesis, migration and invasion is substantially responsible for their chemotherapeutic activity against lung cancer. However, their clinical application is limited due to poor aqueous solubility, low permeability and quick blood clearance, which leads to their low bioavailability. Nanoengineered systems such as liposomes, nanoparticles, micelles, dendrimers and nanotubes can considerably enhance the targeted action of the flavonoids with improved efficacy and pharmacokinetic properties, and flavonoids can be successfully translated from bench to bedside through various nanoengineering approaches. This review addresses the therapeutic potential of various flavonoids and highlights the cutting-edge progress in the nanoengineered systems that incorporate flavonoids for treating lung cancer.
Present study prepared curcumin-loaded nanoliposomes using bovine milk, krill phospholipids and cholesterol; and investigated the effects of cholesterol on membrane characteristics, storage stability and antibacterial properties of the curcumin nanoliposomes. Bovine milk phospholipids which have higher saturation than krill phospholipids resulted in formation of curcumin-loaded nanoliposomes with higher encapsulation efficiency (84.78%), larger absolute value of zeta potential and vesicle size (size: 159.15 ± 5.27 nm, zeta potential: -28.3 ± 0.62 mV). Cholesterol helps to formation of a more hydrophobic, compact and tighter bilayer membrane structure which improved the storage stability of nanoliposomes under alkaline (66.25 ± 0.46%), heat (43.25 ± 0.69%) and sunlight (49.44 ± 1.78%) conditions. In addition, curcumin-loaded nanoliposomes can effectively target infectious bacteria which secrete pore-forming toxins such as Staphylococcus aureus by causing the bacterial cell wall to lysis. Findings from present work can guide future development of novel antibacterial agents for use in food preservation.
Pickering water-in-oil (W/O) emulsions were fabricated by using medium-long chain diacylglycerol (MLCD)-based solid lipid nanoparticles (SLNs) and the connection between the characteristics of the SLNs and the colloidal stability of the emulsions was established. Via melt-emulsification and ultrasonication, MLCD-based SLNs with particle sizes of 120-300 nm were obtained with or without other surfactants. The particle size of the SLNs was influenced by the chemical properties of the surfactants, and surfactants decreased the contact angle of SLNs at the oil-water interface. Gelation was observed in SLNs modified by sodium stearoyl lactylate and lecithin, whereas the addition of Tween 20 resulted in a homogeneous SLN solution. The adsorption of surfactants onto SLN surfaces caused the production of higher amounts of α crystals accompanied by delayed crystallization onset which contributed to the reduction of particle size, interfacial tension and oil wetting ability. The W/O emulsions with higher rigidity and physical stability can be obtained by varying surfactant types and by increasing SLN mass ratios to 60%, whereby more SLNs are adsorbed at the droplet surface as a Pickering stabilizer. This study provides useful insights for the development of diacylglycerol-based SLNs and Pickering W/O emulsions which have great potential for food, cosmetic and pharmaceutical applications.
Inflammatory lung diseases related morbidity and mortality impose a significant financial burden. Inflammation is a hallmark of many diseases of the respiratory system which is directly or indirectly linked to adverse health conditions, air pollution, rapid lifestyle changes, and regular outbreaks of microbial infections. The unique anatomical and physiological features of the lungs make them an ideal target organ in the treatment of inflammatory respiratory disease and with the help of inhaled therapy lungs can be targeted directly. The principal objective of this review is to present the comprehensive role of inhaled nano-based therapeutics such as liposomes, niosomes, nanoparticles, nanoemulsion, nanosuspension, and exosomes in the treatment and management of inflammatory respiratory diseases. Inhaled nanomedicines provide targeted diagnosis and treatment, improved drug solubility and distribution, prevent first-pass hepatic metabolism, improved patient compliance, and reduced drug side effects. They overcome several biological barriers in the human body and provide immediate, and quick-onset of action. Future research should be focused on improving the therapeutic efficiency of inhaled nanocarriers and to carry out in-depth mechanistic studies to translate current scientific knowledge for the efficient management of inflammatory lung diseases with minimal or no toxicity.
Epigenetic inhibitors have shown anticancer effects. Combination chemotherapy with epigenetic inhibitors has shown high effectiveness in gastric cancer clinical trials, but severe side effect and local progression are the causes of treatment failure. Therefore, we sought to develop an acidity-sensitive drug delivery system to release drugs locally to diminish unfavorable outcome of gastric cancer. In this study, we showed that, as compared with single agents, combination treatment with the demethylating agent 5'-aza-2'-deoxycytidine and HDAC inhibitors Trichostatin A or LBH589 decreased cell survival, blocked cell cycle by reducing number of S-phase cells and expression of cyclins, increased cell apoptosis by inducing expression of Bim and cleaved Caspase 3, and reexpressed tumor suppressor genes more effectively in MGCC3I cells. As a carrier, reconstituted apolipoprotein B lipoparticles (rABLs) could release drugs in acidic environments. Orally administrated embedded drugs not only showed inhibitory effects on gastric tumor growth in a syngeneic orthotopic mouse model, but also reduced the hepatic and renal toxicity. In conclusion, we have established rABL-based nanoparticles embedded epigenetic inhibitors for local treatment of gastric cancer, which have good therapeutic effects but do not cause severe side effects.
The anti-inflammatory property of ratite oils as well as its ability to act as a penetration enhancer makes it an ideal agent to be used in transdermal formulations. The present study aims to develop an effective transfersomal delivery of 4-hydroxytamoxifen (4-OHT), an anti-cancer drug, using ratite oil as a carrier agent for the treatment of breast cancer (BC). The 4-OHT transfersomes were prepared with and without ratite oils using soy phosphatidylcholine and three different edge activators (EAs) in five different molar ratios using the rotary evaporation-ultrasonication method. Optimal transfersome formulations were selected using physical-chemical characterization and ex vivo studies. Results from physical-chemical characterization of the developed formulations found sodium taurocholate to be the most suitable EA, which recorded highest entrapment efficiency of 95.1 ± 2.70% with 85:15, (w/w) and lowest vesicle size of 82.3 ± 0.02 nm with 75:25, (w/w) molar ratios. TEM and DSC studies showed that the vesicles were readily identified and present in a nearly perfect spherical shape. In addition, formulations with emu oil had better stability than formulations with ostrich oil. Physical stability studies at 4 °C showed that ratite oil transfersomes were stable up to 4 weeks, while transfersomes without ratite oils were stable for 8 weeks. Ex vivo permeability studies using porcine skin concluded that 4-OHT transfersomal formulations with (85:15, w/w) without emu oil have the potential to be used in transdermal delivery approach to enhance permeation of 4-OHT, which may be beneficial in the treatment of BC.
Nanoliposome and nanoniosome formulations containing myrtle extract were prepared without using cholesterol and toxic organic solvents for the first time. The formulations had different concentrations of lecithin (5, 7, and 9% w/w) and Hydrophilic-Lipophilic Balance (HLB) values (6.76, 8.40, and 9.59). The physicochemical characterization results showed a nearly spherical shape for the prepared nanosamples. The particle sizes, zeta potentials and encapsulation efficiencies for the prepared nanoliposomes and nanoniosomes were at a range of 260-293 nm and 224-520 nm; -33.16 to - 31.16 mV and - 33.3 to - 10.36 mV; and 68-73% and 79-83%, respectively. The formulated nanoniosomes showed better stability during storage time. Besides, the encapsulation efficiency and in vitro release rate of myrtle extract could be controlled by adjusting the lecithin concentration and HLB value. The release of myrtle extract from nanovesicles showed a pH-responsive character. The FTIR analysis confirmed that the myrtle extract was encapsulated in nanovesicles physically.
Introduction: Diabetic neuropathy (DN) is one of the major complications arising from hyperglycaemia in diabetic patients. In recent years polyphenols present in plants have gained attention to treat DN. The main advantages associated with them are their action via different molecular pathways to manage DN and their safety. However, they failed to gain clinical attention due to challenges associated with their formulation development such as lipophilicity,poor bioavailability, rapid systemic elimination, and enzymatic degradation.Area covered: This article includes different polyphenols that have shown their potential against DN in preclinical studies and the research carried out towards development of their nanoformulations in order to overcome aforementioned issues.Expert opinion: In this review various polyphenol based nanoformulations such as nanospheres, self-nanoemulsifying drug delivery systems, niosomes, electrospun nanofibers, metallic nanoparticles explored exclusively to treat DN are discussed. However, the literature available related to polyphenol based nanoformulations to treat DN is limited. Moreover, these experiments are limited to preclinical studies. Hence, more focus is required towards development of nanoformulations using simple and single step process as well as inexpensive and non-toxic excipients so that a stable, scalable, reproducible and non-toxic formulation could be achieved and clinical trials could be initiated.
Aim: To synthesize niosomes co-encapsulating gemcitabine (GEM) and tocotrienols, and physicochemically characterize and evaluate the antipancreatic effects of the nanoformulation on Panc 10.05, SW 1990, AsPC-1 and BxPC-3 cells. Materials & methods: Niosomes-entrapping GEM and tocotrienols composed of Span 60, cholesterol and D-α-tocopheryl polyethylene glycol 1000 succinate were produced by Handjani-Vila and film hydration methods. Results: The film hydration produced vesicles measuring 161.9 ± 0.5 nm, approximately 50% smaller in size than Handjani-Vila method, with maximum entrapment efficiencies of 20.07 ± 0.22% for GEM and 34.52 ± 0.10% for tocotrienols. In Panc 10.05 cells, GEM's antiproliferative effect was enhanced 2.78-fold in combination with tocotrienols. Niosomes produced a significant ninefold enhancement in cytotoxicity of the combination, supported by significantly higher cellular uptake of GEM in the cells. Conclusion: This study is a proof of concept on the synthesis of dual-drug niosomes and their efficacy on pancreatic cancer cells in vitro.