Highly controllable dendritic structural design means dendrimers are a leading carrier in drug delivery applications. Dendrimer- and other nanocarrier-based hybrid systems are an emerging platform in the field of drug delivery. This review is a compilation of increasing reports of dendrimer interactions, such as dendrimer-liposome, dendrimer-carbon-nanotube, among others, known as hybrid carriers. This should prompt entirely new research with promising results for these hybrid carriers. It is assumed that such emerging hybrid nanosystems - from combining two already-established drug delivery platforms - could lead the way for the development of newer delivery systems with multiple applicability for latent theranostic applications in the future.
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.
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.
Topical route of administration is the most commonly used method for the treatment of ophthalmic diseases. However, presence of several layers of permeation barriers starting from the tear film till the inner layers of cornea make it difficult to achieve the therapeutic concentrations in the target tissue within the eye. In order to circumvent these barriers and to provide sustained and targeted drug delivery, tremendous advances have been made in developing efficient and safe drug delivery systems. Liposomes due to their unique structure prove to be extremely beneficial drug carriers as they can entrap both the hydrophilic and hydrophobic drugs. The conventional liposomes had several drawbacks particularly their tendency to aggregate, the instability and leakage of entrapped drug and susceptibility to phagocytosis. Due to this reason, for a long time, liposomes as drug delivery systems did not attract much attention of researchers and clinicians. However, over recent years development of new generation liposomes has opened up new approaches for targeted and sustained drug delivery using liposomes and has rejuvenated the interest of researchers in this field. In this review we present a summary of current literature to understand the anatomical and physiological limitation in achieving adequate ocular bioavailability of topically applied drugs and utility of liposomes in overcoming these limitations. The recent developments related to new generation liposomes are discussed.
Der p 2 is a major dust mite allergen and >80% of mite allergic individuals have specific IgE to this allergen. Although it is well characterized in terms of allergenicity, there is still some ambiguity in terms of its biological function. Three-dimensional structural analysis of Der p 2 and its close homologues indicate the presence of a hydrophobic cavity which can potentially bind to lipid molecules. In this study, we aimed to identify the potential ligand of Der p 2. Using a liposome pulldown assay, we show that recombinant Der p 2 binds to liposomes prepared with exogenous cholesterol in a dose dependent fashion. Next, an ELISA based assay using immobilized lipids was used to study binding specificities of other lipid molecules. Cholesterol was the preferred ligand of Der p 2 among 11 different lipids tested. Two homologues of Der p 2, Der f 2 and Der f 22 also bound to cholesterol. Further, using liquid chromatography-mass spectrometry (LC-MS), we confirmed that cholesterol is the natural ligand of Der p 2. Three amino acid residues of Der p 2, V104, V106 and V110 are possible cholesterol binding sites, as alanine mutations of these residues showed a significant decrease in binding (p
Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug's effects on cardiac function in a rat experimental autoimmune myocarditis (EAM) model. We prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 ± 4.4 nm). We induced EAM by immunization with porcine myosin and assessed the tissue distribution of the nano-sized beads and liposomal FK506 in this model. After liposomal or free FK506 was administered on days 14 and 17 after immunization, the cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal FK506 was administered. The administration of liposomal FK506 markedly suppressed the expression of cytokines, such as interferon-γ and tumor necrosis factor-α, and reduced inflammation and fibrosis in the myocardium on day 21 compared to free FK506. The administration of liposomal FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano-sized liposomes may be a promising drug delivery system for targeting myocarditic hearts with cardioprotective agents.
The aim of this study was to produce and characterise nanosize liposomes containing bioactive peptides with antioxidative and ACE-inhibitory properties, derived from winged bean seeds (WBS) protein. WBS powder was papain-proteolysed, at 70 °C and pH 6.5 for six hours, followed by encapsulation via a solvent-free heating method. The results showed that the WBS proteolysate was successfully incorporated into spherical, unilamellar liposomal particles, with particle diameter, polydispersity index, zeta potential and encapsulation efficiency of 193.3 ± 0.12 nm, 0.4 ± 0.02 (unit less), -70.5 ± 0.30 mV and 27.6 ± 1.17%, respectively. It also demonstrated good storage stability over eight weeks at 4 °C, indicated by slight increment (15.1%) in particle size and a zeta potential only weaker by 17.2% at the end of the study period. These results suggested the feasibility of entrapping water soluble peptides in hydrophobic liposomal system that, upon optimisation, has the potential to act as bioactive food ingredient.
The main objective of this study was to use heating method (HM) to prepare liposome without employing any chemical solvent or detergent. Plackett-Burman design (PBD) was applied for the screening of significant process variables including the lecithin proportion, the cholesterol/lecithin ratio, the pH of solution for liposome preparation, the enzyme/lecithin ratio, the stirring time, the process temperature, the speed of stirrer, the ratio of stirrer to the tank diameter, the application of homogenization, the method of adding enzyme and centrifugation conditions on the encapsulation efficiency (EE %) of liposome and the activity of liposomal Flavourzyme (LAPU(-1)) (P
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.
This study used highly lipophilic agents with an aim to increase the oxidant inhibitory activity and enhance photothermal stability of a novel mixed soy lecithin (ML)-based liposome by changing the composition of formulation within the membrane. Specifically, the development and optimization of the liposome intended for improving Trolox equivalent antioxidant capacity (TEAC) value and %TEAC loss was carried out by incorporating a natural antioxidant, quercetin (QU). In this context, a focus was set on QU encapsulation in ML-based liposomes and the concentration-dependent solubility of QU was investigated and calculated as encapsulation efficiency (EE). To explore the combined effects of the incorporation of plant sterols on the integrity and entrapment capacity of mixed phospholipid vesicles, conjugation of two types of phytosterols (PSs), namely β-sitosterol (βS) and stigmasterol (ST), to mixed membranes at different ratios was also performed. The EE measurement revealed that QU could be efficiently encapsulated in the stable ML-based liposome using 0.15 and 0.1 g/100 mL of βS and ST, respectively. The aforementioned liposome complex exhibited a considerable TEAC (197.23%) and enhanced TEAC loss (30.81%) when exposed to ultraviolet (UV) light (280-320 nm) over a 6 h duration. It appeared that the presence and type of PSs affect the membrane-integration characteristics as well as photodamage transformation of the ML-based liposome. The association of QU with either βS or ST in the formulation was justified by their synergistic effects on the enhancement of the EE of liposomes. Parallel to this, it was demonstrated that synergistic PS effects could be in effect in the maintenance of membrane order of the ML-based liposome. The findings presented in this study provided useful information for the development and production of stable QU-loaded ML-based liposomes for food and nutraceutical applications and could serve as a potential mixed lipids-based delivery system in the disease management using antioxidant therapy.
Cancer and tumor have been major reasons for numerous deaths in this century across the world. Many strategies have been designed to treat, diagnose, or prevent cancer. The success of chemotherapy largely depends on drug targeting. The advent of nanotechnology has vastly improved drug delivery for targeting and diagnosis. Nevertheless, the accuracy of drug targeting with polymeric nanoparticles has always been questionable. The polymeric nanoparticles synthesized from varieties of lipid-based compounds or combined with vectors, such as liposomes, ethosomes, and transfersomes, may allow the drug to overcome the issue of resistance to drug absorption in biological membranes. The combined effects of lipid-based nanocarriers are known to improve the efficacy and accuracy of polymeric nanoparticles. The present review explores the application of lipid based nanocarriers in the treatment and diagnosis of cancer A special focus is given to the use of lipid-based nanocarriers in the treatment, diagnosis, and mitigation of cancer located in blood, brain, lung, and colon. The treatment of these cancers has always been questionable as the chances of relapse are very high. The review encompasses the use of lipid-based nanocarriers in targeting tissue-specific cancer cells.
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.
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.
The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.
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.
Nanotechnology science has been diverged its application in several fields with the advantages to operate with nanometric range of objects. Emerging field of nanotechnology has been also being approached and applied in medical biology for improved efficacy and safety. Increased success in therapeutic field has focused several approaches in the treatment of the common metabolic disorder, diabetes. The development of nanocarriers for improved delivery of different oral hypoglycemic agents compared to conventional therapies includes nanoparticles (NPs), liposomes, dendrimer, niosomes and micelles, which produces great control over the increased blood glucose level and thus becoming an eye catching and most promising technology now-a-days. Besides, embellishment of nanocarriers with several ligands makes it more targeted delivery with the protection of entrapped hypoglycaemic agents against degradation, thereby optimizing prolonged blood glucose lowering effect. Thus, nanocarriers of hypoglycemic agents provide the aim towards improved diabetes management with minimized risk of acute and chronic complications. In this review, we provide an overview on distinctive features of each nano-based drug delivery system for diabetic treatment and current NPs applications in diabetes management.
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.
In this work, we studied whether chondroitin sulfates and dextran sulfates (DXSs) can influence hypochlorite-induced peroxidation of phosphatidylcholine (PC) liposomes. Multilamellar liposomes (2 mg lipid/ml) were prepared in phosphate buffer, pH 7.4, with NaCl or not and exposed to reagent HOCl/ClO- (1mM) at 37 degrees C in the presence of different concentrations of chondroitin 6-sulfate (C6S), chondroitin 4-sulfate (C4S), DXS 8000, DXS 40,000, and DXS 500,000. Lipid peroxidation was assessed by thiobarbituric acid-reactive substance (TBARS) production. DXSs and C6S enhanced TBARS production in a dose-dependent manner. The decline in TBARS production at the relatively high C6S concentrations may be attributed to C4S present in C6S, since in contrast to C6S, C4S is known to react with hypochlorite. Dextrans, nonsulfated analogues of DXS, failed to modulate TBARS production. This fact indicates the important role of negatively charged sulfate groups for DXS to facilitate hypochlorite-induced peroxidation of PC liposomes. The electrostatic nature of the mechanism providing for the pro-oxidative effect of DXS was also supported by the influence of liposome surface charge and solution ionic strength on the extent of liposome peroxidation. The addition of calcium ions to the incubation mixture did not prevent the pro-oxidative action of DXS. The relevance of the results to atherogenesis is discussed.
Ethosomal systems are novel lipid vesicular carriers containing a relatively high percentage of ethanol. These nanocarriers are especially designed for the efficient delivery of therapeutic agents with different physicochemical properties into deep skin layers and across the skin. Ethosomes have undergone extensive research since they were invented in 1996; new compounds were added to their initial formula, which led to the production of new types of ethosomal systems. Different preparation techniques are used in the preparation of these novel carriers. For ease of application and stability, ethosomal dispersions are incorporated into gels, patches, and creams. Highly diverse in vivo models are used to evaluate their efficacy in dermal/transdermal delivery, in addition to clinical trials. This article provides a detailed review of the ethosomal systems and categorizes them on the basis of their constituents to classical ethosomes, binary ethosomes, and transethosomes. The differences among these systems are discussed from several perspectives, including the formulation, size, ζ-potential (zeta potential), entrapment efficiency, skin-permeation properties, and stability. This paper gives a detailed review on the effects of ethosomal system constituents, preparation methods, and their significant roles in determining the final properties of these nanocarriers. Furthermore, the novel pharmaceutical dosage forms of ethosomal gels, patches, and creams are highlighted. The article also provides detailed information regarding the in vivo studies and clinical trials conducted for the evaluation of these vesicular systems.
Several vesicular systems loaded with curcumin have found their way in the therapeutic applications of several diseases, primarily acting through their immunological pathways. Such systems use particles at a nanoscale range, bringing about their intended use through a range of complex mechanisms. Apart from delivering drug substances into target tissues, these vesicular systems also effectively overcome problems like insolubility and unequal drug distribution. Several mechanisms are explored lately by different workers, and interest over vesicular curcumin has been renewed in the past decade. This commentary discusses several immunological targets in which curcumin is employed in a vesicular form.