Vesicular Nanocarriers Research Articles

Solusomes (novel soluplus® enriched nano-vesicular carriers) for improving the oral bioavailability of Candesartan cilexetil

Candesartan cilexetil (CAN) is administered for treating hypertension and heart failure. CAN suffers poor oral bioavailability, owing to limited aqueous solubility, and first-pass metabolism. Solusomes (novel Soluplus® enriched nano-vesicular carriers) combine the merits of Soluplus®, and the traditional liposomes. They were explored to increase CAN solubility, allow a high drug release rate, and improve the oral drug bioavailability. Solusomes were developed via thin film hydration technique utilizing lipid (phosphatidylcholine; PC) and polymeric solubilizer (Soluplus®; Solu). S6 system comprising PC (0.1% w/v), CAN and Soluplus® (at 1:5 ratio; w/w), following a 5 min sonication period, was the optimum one with respect to drug entrapment efficiency (83.5 ± 2.6%), drug loading (11.9 ± 0.3%), particle size and shape (377.2 ± 12.1 nm, spherical), zeta-potential (−19.6 ± 2.1 mV), saturated drug solubility (32.09 ± 0.71 µg/mL), drug released % after 1 h (68 ± 0.9%), and stability. Significantly higher Cmax (969.12 ± 46.3 ng/mL), shorter median Tmax (1h), and improved relative bioavailability (≈ 6.8 folds) in rabbits could evidence the potential of S6 system in enhancing oral CAN bioavailability. S6 solusomes act as dual platform to improve the oral drug bioavailability and maintain effective drug concentration for a prolonged period.

Bilosomes as Soft Nanovesicular Carriers for Ropinirole Hydrochloride: Preparation and In- vitro Characterization

Bilosomes are nanovesicular carriers that contain bile salts and non-ionic surfactants in a bilayer with cholesterol. These are more ultra-deformable, elastic, and flexible than other nanovesicular carrier.Ropinirole hydrochloride (RH) is a non-ergot dopamine D2-agonist. It is used to manage Parkinson's disease and to minimize "on-off" variations in levodopa responsiveness. The oral bioavailability is about 50% due to it being extensively metabolized in the liver, with an elimination half-life of about 6 h.The aim of this study was to enhance oral drug delivery and provide the sustained release of RH by preparing it as soft nanovesicular carriers (bilosomes).Eight formulas of RH bilosomes were prepared by a reverse-phase evaporation method using mixed surfactant (span®60: tween®60 at 1:2 ratio), cholesterol and sodium deoxycholate as bile salt.All formulas were evaluated for their drug content, entrapment efficiency, vesicle size, polydispersity index, zeta potential, drug release, transmission electron microscopy and fourier transform infrared spectroscopy.Results showed all prepared RH bilosomes were in nano-range with vesicle size ranging (from 124.40±10.60 to 294.60±11.50) nm, Zeta potential ranged (from -16.955±7.372 to -23.22±0.880) mV and with entrapment efficiency % ranged (from 57.30±6.48% to 77.77±3.78%).
 The best formula F5 showed vesicle size (160.60±15.82) nm, Zeta potential (-20.75±0.930) mV, and entrapment efficiency %(77.77±3.78%) with 84.39% in-vitro release of RH after 24 h.It is concluded that bilosomes are good nanovesicular carriers for enhancing oral drug delivery and providing the sustained release of RH and all that may enhance oral bioavailability for RH.

Anticancer Effects of Date Seed Oil- Loaded Niosomes and Gemcitabine Combination in MCF-7 Human Breast Cancer Cells

Gemcitabine (GEM) is one of the most widely used chemotherapeutic medications for treating various solid tumuors. Niosomes are a novel drug delivery system, self-assembled vesicular nanocarriers and composed of several surfactants and various lipids. Date seed Oil (DSO) contain a high percentage of phenolic and flavonoid compounds that making them important for food and pharmaceutical formulations. In this study, we prepared GEM loaded into anionic niosomes (GEM-niosomes) to target breast tumor cells. The niosomes were prepared with cholesterol (CHOL), span 60, date seed oil and chloroform using the thin film hydration method. GEM-niosomes were fully characterized for their physiochemical properties and evaluated for their cytotoxicity. The targeted niosomes were 100±10nm, the loaded niosomes were in the range of 125±15. GEM-fully loaded DSO-niosomes with drug entrapment percentage (EE%) 82% using high- performance liquid chromatography (HPLC) were developed. The prepared targeted GEM-niosomes showed good stability over 4 weeks at -7ºC and better drug loading. Our targeted GEM-niosomes showed stronger activity against MCF-7 cell by approximately 10 folds compared with the free drug. Taken together, the combination of GEM and “DSO- loaded niosomes” may be of great importance for developing new treatments following in vivo investigations with breast cancer animal models. Future research should explore the in vitro and the in vivo cytotoxicity of this combination on more aggressive breast cancer ( BC).

Effects of Different Types of Bile Salts on the Physical Properties of Ropinirole-Loaded

Background: Bilosomes are vesicular nanocarriers that contain bile salts, making them more flexible and resistant to degradation in the gastrointestinal tract. Objective: To evaluate the effect of two bile salts on the physical properties and stability of the ropinirole-loading bilosome. Methods: Sixteen bilosomal formulations were prepared by a reverse-phase evaporation method. Each formula includes a mixture of non-ionic surfactants (Span®60 and Tween®60), along with cholesterol and bile salts (either sodium taurocholate (STC) or sodium glycocholate (SGC). The characteristics of the bilosomal formulations (drug content, entrapment efficiency, vesicle size, polydispersity index, zeta potential, in-vitro drug release, and Fourier transform infrared spectroscopy) were evaluated. Results: The entrapment efficiency of ropinirole was reduced by using sodium glycocholate instead of sodium taurocholate. The vesicle size and zeta potential were also affected by the type of bile salt and its amount. Drug release profiles were sustained, indicating a good entrapment of ropinirole. The STC-containing bilosomes are more stable than the SGC-containing bilosomes. Bilosomal formula F5 showed the highest entrapment efficiency (64.82%), suitable vesicle size (179.8 nm), zeta potential (-9.162 mV), polydispersity index (0.5116), and in vitro drug release (62.33%) after 24 hr. Conclusion: Sodium taurocholate was more suitable for the preparation of ropinirole-loading bilosomes, with more stability of bilosomes in bile salt solution.

Unlocking the potential of cosmetic dermal delivery with ethosomes: A comprehensive review.

In a world where hair loss, acne, and skin whitening are common concerns, ethosomes emerge as a captivating breakthrough in cosmetic drug delivery. This review provides a comprehensive overview of the ethosomal system and assesses its potential as an effective nanocarrier for delivering active ingredients to the skin. The focus is on exploring their applications in various pathologies, particularly skin disorders such as acne, hair loss, and skin pigmentation. Ethosomes are a novel type of vesicular nanocarrier composed of high concentrations of ethanol (20-45%) and phospholipids. Their unique structure and composition make them an ideal choice for transporting active ingredients through the skin, offering targeted and effective treatment. The inclusion of ethanol in ethosomes' composition gives them distinctive properties, including flexibility, deformability, and stability, facilitating deep penetration into the skin and enhancing medication deposition. Moreover, ethosomes improved theoverall drug-loading capacity, and specificity of target treatment CONCLUSION: Ethosomes represent a unique and suitable approach for delivering active cosmetic ingredients in the treatment of hair loss, acne, and skin whitening, presenting a versatile alternative to traditional dermal delivery systems. Despite the challenges associated with their complex preparation and sensitivity to temperature and humidity, the remarkable potential benefits of ethosomes cannot be ignored. Further research is crucial to unlock their full potential, understand their limitations, and refine their formulations and administration methods. Ethosomes hold the promise of transforming the way we address these cosmetic concerns, offering an exciting glimpse into the future of advanced skincare solutions.

Elegant, Flexible Vesicular Nanocarriers for the Efficient Skin Delivery of Topically Applied Drugs

Background: Skin diseases represent a major health concern worldwide and negatively impact patients’ quality of life. Despite the availability of various efficacious drugs, their therapeutic outcome is often limited due to shortcomings related to the formidable skin barrier and unfavorable physicochemical properties of drugs. Flexible nano-vesicles have shown tremendous potential to overcome these hurdles and improve the local therapeutic effect of these drugs. Objective: This review article is aimed to shed light on flexible nano-vesicular carriers as a means to combat skin diseases. Methods: The literature was reviewed using PubMed database using various keywords such as liposomes, flexible (deformable liposomes) (transferosomes), ethosomes, transethosomes, niosomes, and spanlastics. Results: Liposomes and niosomes were found effective for the loading and release of both hydrophilic and lipophilic drugs. However, their limited skin penetration led to drug delivery to the outermost layers of skin only. This necessitates the search for innovative vesicular carriers, including liposomes, flexible (deformable liposomes), ethosomes, transethosomes, and spanlastics. These flexible nano-vesicular carriers showed enhanced drug delivery and deposition across various skin layers, which was better than their corresponding conventional vesicles. This resulted in superior drug efficacy against various skin diseases such as skin cancer, inflammatory skin diseases, superficial fungal infections, etc. Conclusion: Flexible nano-vesicular carriers have proven themselves as efficient drug delivery systems that are able to deliver their cargo into the deep skin layers and thus, improve the therapeutic outcome of various skin diseases. However, there remain some challenges that need to be addressed before these nanocarriers can be translated from the lab to clinics.

Brief Insight on Nanovesicular Liposomes as Drug-delivery Carriers for Medical Applications

Nanotechnology has revolutionized and improved the potential of drug-delivery systems. Lipidic nanovesicles, termed liposomes, offer several benefits as drug-delivery carriers due to their compositional similarity with human biological membranes. Some of the advantages offered by liposomes include targeted drug delivery and improved pharmacokinetics of an entrapped drug substance, leading to enhanced bioavailability. Additionally, the reduction in the drug dose or dosing frequency, reduced drug toxicity or side effects, longer and controlled therapeutic response of a drug essential for the treatment of chronic diseases, and improved patient acceptance margins are some other benefits offered by liposomes. The easily modifiable surface of liposomes makes it an ideal vehicle for targeting a drug to the desired site. The current review provides insight on liposomes as drug-delivery carriers. This review summarizes the classification of compositional constituents of liposomes based on their chemical nature and structure. Morphology-based classification of liposomes along with methods of preparation and characterization for liposomes are also summarized. The current review emphasizes the medical applications of liposomes, specifically as delivery carriers for therapeutic and diagnostic agents. The article features detailed therapeutic applications of liposomes based on routes of administration and specific disease conditions. Diagnostic applications of liposomes for improving the efficiency of available techniques to treat diseases such as cancer are also discussed. Liposomes are thus reviewed as multifaceted nanovesicular carriers with potential therapeutic and diagnostic medical applications. The prospective multifunctional application of combining imaging functionality with therapeutic agents in a single liposome for diagnosis and real-time treatment is anticipated to be the future of liposomal formulations.

Non-lamellar lipid liquid crystalline nanoparticles: A smart platform for nanomedicine applications

The increased interest of the scientific community in lipid nanoparticles has pushed the boundaries of personal medicine and drug delivery. The focus has been set on vesicular nanocarriers, as their structure and functionalities have been well described, but the application of their non-lamellar counterparts, cubosomes and hexosomes, has shown their potency as drug carriers. In addition, the sponge phase dispersion (L3, an intermediate between the lamellar and the bicontinuous cubic) has also been proved effective for the encapsulation of large macromolecules. Their physicochemical characterization has improved in the past decades due to the investigations conducted at high-power synchrotron facilities and the application of surface-sensitive techniques, discovering new connections between physical parameters and biological performance. Several administration routes of cubosomes and hexosomes have been studied, such as intravenous, dermal, transdermal, and oral, to evaluate their cytotoxicity and distribution in biological media. This review aims to summarize the challenges and recent achievements of cubosomes, hexosomes, and sponge nanoparticles as suitable carriers for the administration of bioactives.

Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug Delivery.

Poor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low permeable compounds into and across the skin. This research work was to design, develop and optimize levosulpiride-loaded niosomal gel and to evaluate its prospects for transdermal delivery. The Box-Behnken design was used to optimize niosomes by analyzing the impact of three factors (cholesterol; X1, Span 40; X2, and sonication time; X3) on the responses (particle size, Y1, and entrapment efficiency, Y2). Optimized formulation (NC) was incorporated into gel and evaluated for pharmaceutical properties, drug release study, ex vivo permeation, and in vivo absorption. The design experiment data suggest that all three independent variables influence both response variables significantly (p < 0.01). Pharmaceutical characteristics of NC vesicles showed the absence of drug excipient interaction, nanosize (~102.2 nm), narrow distribution (~0.218), adequate zeta potential (-49.9 mV), and spherical shape, which are suitable for transdermal therapy. The levosulpiride release rates varied significantly (p < 0.01) between niosomal gel formulation and control. Greater flux (p < 0.01) was observed with levosulpiride-loaded niosomal gel than with control gel formulation. Indeed, the drug plasma profile of niosomal gel was significantly higher (p < 0.005), with ~3 folds higher Cmax and greater bioavailability (~500% higher; p < 0.0001) than its counterpart. Overall, these findings imply that the use of an optimized niosomal gel formulation can increase the therapeutic efficacy of levosulpiride and may represent a promising alternative to conventional therapy.

T7 peptide-decorated exosome-based nanocarrier system for delivery of Galectin-9 siRNA to stimulate macrophage repolarization in glioblastoma.

Exosomes are nano-vesicular carriers capable of delivering cargoes for intercellular communication, which holds potential as biocompatible and high efficiency systems for drug delivery. In this study, we evaluated the potential effect of T7 peptide-decorated exosome-loaded Galectin-9 siRNA (T7-Exo/siGalectin-9) in the M1 polarization of macrophages and immunosuppression of glioblastoma (GBM). Differentially expressed genes in GBM were in silico predicted and then experimentally verified. Galectin-9 was knocked down by siRNA to assess its role in tumor-bearing mice. T7 peptide-decorated exosomes (derived from human embryonic kidney [HEK]-293T cells) targeting GBM were prepared, and loaded with Galectin-9 siRNA by electroporation to prepare nanoformulations (T7-Exo/siGalectin-9). The role of T7-Exo/siGalectin-9 in CD8+ T cell cytotoxicity to target GBM cells and polarization of macrophages was evaluated after artificial modulation of Galectin-9 expression. Anti-tumor effects of T7-Exo/siGalectin-9 were elucidated in vitro and in vivo. Galectin-9 was highly expressed in GBM tissues and cell lines. The siRNA-mediated knockdown of Galectin-9 repressed the growth of xenografts of GBM cells in C57BL/6 mice and activated immune response in the tumor microenvironment. T7-Exo/siGalectin-9 effectively delivered siGalectin-9 to GBM cells. T7-Exo/siGalectin-9 contributed to activation of the TLR7-IRF5 pathway, which polarized macrophages to M1 phenotype. By this mechanism, phagocytosis of GBM cells by macrophages was increased, the anti-tumor effect of CD8+ T cells was enhanced and the inflammatory responses were suppressed. Overall, T7-Exo/siGalectin-9 promotes macrophage repolarization and restricts the immunosuppression of GBM, thus providing novel insights into and drug delivery system of immunotherapy for GBM.

PEGylated and functionalized polylactide-based nanocapsules: An overview

Polymeric nanocapsules (NC) are versatile mixed vesicular nanocarriers, generally containing a lipid core with a polymeric wall. They have been first developed over four decades ago with outstanding applicability in the cosmetic and pharmaceutical fields. Biodegradable polyesters are frequently used in nanocapsule preparation and among them, polylactic acid (PLA) derivatives and copolymers, such as PLGA and amphiphilic block copolymers, are widely used and considered safe for different administration routes. PLA functionalization strategies have been developed to obtain more versatile polymers and to allow the conjugation with bioactive ligands for cell-targeted NC. This review intends to provide steps in the evolution of NC since its first report and the recent literature on PLA-based NC applications. PLA-based polymer synthesis and surface modifications are included, as well as the use of NC as a novel tool for combined treatment, diagnostics, and imaging in one delivery system. Furthermore, the use of NC to carry therapeutic and/or imaging agents for different diseases, mainly cancer, inflammation, and infections is presented and reviewed. Constraints that impair translation to the clinic are discussed to provide safe and reproducible PLA-based nanocapsules on the market. We reviewed the entire period in the literature where the term “nanocapsules” appears for the first time until the present day, selecting original scientific publications and the most relevant patent literature related to PLA-based NC. We presented to readers a historical overview of these Sui generis nanostructures.

Film Forming Systems for Delivery of Active Molecules into and across the Skin

We have investigated delivery systems that can form a structured matrix film on the skin after their application. In a previous work, we have shown that Weblike film forming systems (also called Pouches Drug Delivery Systems, PDDS) enable enhanced skin delivery of the incorporated molecules. These delivery systems are composed of one or more phospholipids, a short-chain alcohol, a polymer and optionally water. In this work, we continue the investigation and characterization of Weblike carriers focusing on some factors affecting the delivery properties such as components concentration and mode of application on the skin. Upon non-occluded application on the skin, the systems dry rapidly, forming a web-like structured film. Lidocaine, Ibuprofen, FITC and Cannabidiol are molecules with various physico-chemical properties that were incorporated in the carrier. The systems were tested in a number of in vitro and in vivo experiments. Results of the in vitro permeation of Ibuprofen through porcine skin indicated two-fold delivery through the skin of Ibuprofen when applied from our Weblike system in comparison with a nanovesicular carrier, the ethosome. We also have investigated weblike systems containing hemp seed oil (HSO). This addition enhanced the film's ability to deliver lipophilic molecules to the deeper skin layers, leading to an improved pharmacodynamic effect. In analgesic tests carried out in a pain mice model following one hour application of CBD in Weblike system with and without HSO, the number of writhing episodes was decreased from 29 in the untreated animals to 9.5 and 18.5 writhes, respectively. The results of our work open the way towards a further investigation of Weblike film forming systems containing drugs for improved dermal and transdermal treatment of various ailments.

Formulation and characterization of lamotrigine nasal insert targeted brain for enhanced epilepsy treatment

Lamotrigine. (LMT) is a triazine drug has an antiepileptic effect but with low water solubility, dissolution rate and thus therapeutic effect. Spanlastics are nano-vesicular carriers’ act as site-specific drug delivery system. Intranasal route could direct the drug from nose to brain and provide a faster and more specific therapeutic effect. Therefore, this study aimed to upload lamotrigine onto nano-vesicles using spanlastic nasal insert delivery for effective epilepsy treatment via overcoming lamotrigine’s low solubility and improving its bioavailability. Lamtrigine-loaded nano-spanlastic vesicles were prepared by ethanol injection method. To study different formulation factor’s effect on formulations characters; particle size (PS), Zeta potential (ZP), polydispersity index (PDI), entrapment efficiency percentage (EE%) and LMT released amount after 6 h (Q6h); 2^1 and 3^1 full factorial designs were employed. Optimized formula was loaded in lyophilized nasal inserts formulation which were characterized for LMT release and mucoadhesion. Pharmacokinetics studies in plasma and brain were performed on rats to investigate drug targeting efficiency. The optimal nano-spanlastic formulation (F4; containing equal Span 60 amount (100 mg) and edge activator; Tween 80) exhibited nano PS (174.2 nm), high EE% (92.75%), and Q6h > 80%. The prepared nasal inserts (S4) containing 100 mg HPMC has a higher mucoadhesive force (9319.5 dyne/cm2) and dissolution rate (> 80% within 10 min) for rapid in vivo bio-distribution. In vivo studies showed considerable improvement brain and plasma’s rate and extent absorption after intranasal administration indicating a high brain targeting efficiency. The results achieved indicate that nano-spanlastic nasal-inserts offer a promising LMT brain targeting in order to maximize its antiepileptic effect.

Advancement of Niosomal Transdermal Targeting Drug Delivery System

Traditional methods for applying medications to the skin include a variety of methods. Transdermal has been a popular method of drug delivery in recent years for a variety of medications that are challenging to administer in other ways. Transdermal drug delivery has a number of benefits, chief among them the prevention of first-pass metabolism and the stomach environment, which would render the drug inactive. In addition to discussing in depth the various formulation techniques and permeability enhancement for improved therapeutic efficacy, this review covers the fundamental anatomy of the skin that is pertinent to the transdermal route as a drug delivery method. The evaluation sums up the technologies that are now available on the market and discusses the path they are headed in. A transdermal patch offers a controlled release of medicine into the patient, typically through either membrane pores casing a reserve of medication or over body heat melting thin layers of medication entrenched in the adhesive. This is a bonus of transdermal drug transport over different drug transport styles, including like oral, topical, I. V., I. M., etc. The skin is a very real barrier; in this way, drug molecules are modest enough to permeate the skin and can be administered in this way. Typically, the basic disadvantage of transdermal administration systems. Transdermal patches for a wide run of solutions are now readily available. With properties like improved penetration of drug, a sustained sedate discharge by local depot, and modulating systemic absorption of drugs through the skin by a membrane which limits rate, niosomes are vesicular nanocarriers that are getting to be more and more well known as a potential transdermal drug delivery framework. Niosomes are non-ionic surfactant-based vesicles that are more stable, biodegradable, and generally harmless. Niosomes are ideal to liposomes since surfactants are more chemically stable than lipids. The concept of niosome, its benefits and disadvantages, composition, method of preparation, variables influencing niosomes, definition and characterization, and use of niosome are the main topics of this review study. Niosomes can be used to treat a variety of illnesses, including psoriasis, leishmaniasis, cancer, migraines, Parkinson’s disease, etc. Niosomes can help in diagnosis. Niosomal administration can be done intramuscularly, intravenously, orally, or it can be used topically.

Differences in Human Plasma Protein Interactions between Various Polymersomes and Stealth Liposomes as Observed by Fluorescence Correlation Spectroscopy.

A significant factor hindering the clinical translation of polymersomes as vesicular nanocarriers is the limited availability of comparative studies detailing their interaction with blood plasma proteins compared to liposomes. Here, polymersomes are self-assembled via film rehydration, solvent exchange, and polymerization-induced self-assembly using five different block copolymers. The hydrophilic blocks are composed of anti-fouling polymers, poly(ethylene glycol) (PEG) or poly(2-methyl-2-oxazoline) (PMOXA), and all the data is benchmarked to PEGylated "stealth" liposomes. High colloidal stability in human plasma (HP) is confirmed for all but two tested nanovesicles. In situ fluorescence correlation spectroscopy measurements are then performed after incubating unlabeled nanovesicles with fluorescently labeled HP or the specific labeled plasma proteins, human serum albumin, and clusterin (apolipoprotein J). The binding of HP to PMOXA-polymersomes could explain their relatively short circulation times found previously. In contrast, PEGylated liposomes also interact with HP but accumulate high levels of clusterin, providing them with their known prolonged circulation time. The absence of significant protein binding for most PEG-polymersomes indicates mechanistic differences in protein interactions and associated downstream effects, such as cell uptake and circulation time, compared to PEGylated liposomes. These are key observations for bringing polymersomes closer to clinical translation and highlighting the importance of such comparative studies.

Immunocyte Derived Exosomes: Insight into the Potential Chemo-immunotherapeutic Nanocarrier Targeting the Tumor Microenvironment.

"Cancer" is a dreadful immune-pathological condition that is characterized by anti-inflammatory and tumorigenic responses, elicited by the infiltrating immune cells in the vicinity of an uncontrollably proliferative tumor in the tumor microenvironment (TME). The TME offers a conducive microenvironment that supports cancer cell survival by modulating the host immune defense. Recent advancement in exosomal research has shown exosomes, originating from immune cells as well as the cancer cells, have immense potential for suppressing cancer progression and survival in the TME. Additionally, exosomes, irrespective of their diverse sources, have been reported to be efficient nanocarriers for cancer therapeutics with the ability for targeted delivery due to their biogenic nature, ease of cellular uptake, and scope for functionalization with biomolecules like peptides, aptamers, targeting ligands, etc. Immune cell-derived exosomes per se have been found efficacious against cancer owing to their immune-stimulant properties (in either naive or antigen primed form) even without loading any of cancer therapeutics or targeting ligand conjugation. Nevertheless, exosomes are being primarily explored as nanovesicular carriers for therapeutic molecules with different loading and targeting strategies, and the synergism between immunotherapeutic behavior of exosomes and the anticancer effect of the therapeutic molecules is yet to be explored. Hence, this review focuses specifically on the possible strategies to modulate the immunological nature of the source immune cells to obtain immune stimulant exosomes and bring these into the spotlight as chemo-immunotherapeutic nanovesicles, that can easily target and modulate the TME.

Electrostatic anti-CD33-antibody–protamine nanocarriers as platform for a targeted treatment of acute myeloid leukemia

BackgroundAcute myeloid leukemia (AML) is a fatal clonal hematopoietic malignancy, which results from the accumulation of several genetic aberrations in myeloid progenitor cells, with a worldwide 5-year survival prognosis of about 30%. Therefore, the development of more effective therapeutics with novel mode of action is urgently demanded. One common mutated gene in the AML is the DNA-methyltransferase DNMT3A whose function in the development and maintenance of AML is still unclear. To specifically target “undruggable” oncogenes, we initially invented an RNAi-based targeted therapy option that uses the internalization capacity of a colorectal cancer specific anti-EGFR-antibody bound to cationic protamine and the anionic siRNA. Here, we present a new experimental platform technology of molecular oncogene targeting in AML.MethodsOur AML-targeting system consists of an internalizing anti-CD33-antibody–protamine conjugate, which together with anionic molecules such as siRNA or ibrutinib-Cy3.5 and cationic free protamine spontaneously assembles into vesicular nanocarriers in aqueous solution. These nanocarriers were analyzed concerning their physical properties and relevant characteristics in vitro in cell lines and in vivo in xenograft tumor models and patient-derived xenograft leukemia models with the aim to prepare them for translation into clinical application.ResultsThe nanocarriers formed depend on a balanced electrostatic combination of the positively charged cationic protamine-conjugated anti-CD33 antibody, unbound cationic protamine and the anionic cargo. This nanocarrier transports its cargo safely into the AML target cells and has therapeutic activity against AML in vitro and in vivo. siRNAs directed specifically against two common mutated genes in the AML, the DNA-methyltransferase DNMT3A and FLT3-ITD lead to a reduction of clonal growth in vitro in AML cell lines and inhibit tumor growth in vivo in xenotransplanted cell lines. Moreover, oncogene knockdown of DNMT3A leads to increased survival of mice carrying leukemia patient-derived xenografts. Furthermore, an anionic derivative of the approved Bruton’s kinase (BTK) inhibitor ibrutinib, ibrutinib-Cy3.5, is also transported by this nanocarrier into AML cells and decreases colony formation.ConclusionsWe report important results toward innovative personalized, targeted treatment options via electrostatic nanocarrier therapy in AML.

Oleic acid-based vesicular nanocarriers for topical delivery of the natural drug thymoquinone: Improvement of anti-inflammatory activity.

The topical administration of a drug compound remains the first choice for the treatment of many local skin ailments. Many skin diseases can be treated by applying the active formulation directly to the skin, but unfortunately some drugs are unable to overcome the stratum corneum and exert their pharmacological action. An example is thymoquinone, a naturally derived drug obtained from Nigella sativa L. and potentially effective in the treatment of inflammatory and oxidative skin conditions. Since its physico-chemical properties are not suitable for overcoming the stratum corneum, we wanted to circumvent the problem by proposing new lipid-based nanovesicles called "oleoethosomes", made up of naturally derived ingredients, for its delivery. Among several formulations of oleoethosomes, the sample made up of 2% (w/w) oleic acid:PL90G 1:1 (molar ratio), and ethanol 15% showed the best physico-chemical characteristics and above all it showed the capacity to contain a suitable amount of thymoquinone (2mg/ml). The formulation was tested in vitro on stratum corneum and viable epidermis membranes confirming its ability to induce the passage of thymoquinone through the human stratum corneum and to act as a permeation enhancer. In fact, it showed thymoquinone permeation values of 22.63±1.49% regarding the applied drug amount. Oleoethosomes were compared with oleosomes, another kind of naturally derived nanosystems but free of ethanol. The experimental data confirmed that ethanol was an important component that enhanced the activity of the oleoethosomes when tested on the skin of healthy volunteers. The thymoquinone-loaded oleoethosome treatment demonstrated a significantly greater extent of anti-inflammatory activity than the treatment with thymoquinone-loaded oleosomes or the conventional dosage form of the drug. These in vivo results confirmed the synergic effect between oleic acid and ethanol on the lipid and protein compartments of the outermost skin layer, thus promoting a greater penetration capacity.

Vesicular Approach Review on Nanocarriers bearing Curcumin and Applications.

Phytoconstituents have been used to treat a variety of human diseases for a long time, but their use in pharmaceuticals is limited because of their low aqueous solubility. Researchers have created vesicular systems to address many of the issues associated with the bioavailability and therapeutic efficacy of poorly water-soluble drugs and target the drug to the desired location in the body. Several vesicular nanocarrier systems have been developed. Review contrasts various vesicular drug delivery systems, including liposomes, sphingosomes, emulsomes, niosomes, ethosomes, virosomes, phytosomes, aquasomes, proniosomes, transfersomes, pharmacosomes. Vesicular drug delivery systems have caused a scientific revolution, which has resulted in the development of novel dosage forms. This review aims to illustrate the applications, advantages, and disadvantages of the vesicular approach as nanocarriers bearing curcumin and widely used in gene delivery, tumor-targeting to the brain, oral formulations, and resolving various problems associated with drug stability and permeability issues. Nanocarriers also has wide application as green nanocomposites and for antitubercular drugs depending on their physical properties.

PHARMACEUTICAL NIOSOMES DRUG DELIVERY: A COMPLETE REVIEW OF NEW DELIVERY SYSTEM

Over the past ten years, people working in the field of drug delivery systems have become increasingly interested in designing vesicles as a tool to improve drug delivery. A hydrating mixture of cholesterol and nonionic surfactants forms niosomes, which are vesicles. Liposomes, microspheres, engineering science,small emulsions, antibody loaded drug delivery , magnetic microcapsules,implantable pumps, and niosomes are just a few of the unique methods employed to administer these medications. There are two requirements before designing and developing a novel drug delivery system (NDDS). It must first spread the medication at a preset rate and then release an amount of medication at the site of action that is therapeutically efficacious. These requirements cannot be satisfied by conventional dose forms. In essence, niosomes are non-ionic surfactant-based vesicles in which a group of surfactant macromolecules forms a bilayer to form a membrane that entirely seals off an aqueous solution of solute. Targeted medication delivery is made possible by the reasonable circulation persistence of niosomes. An overview of niosome preparation techniques, niosome kinds, characterisation, and applications is also included in this paper.&#x0D; &#x0D; Due to qualities including improved drug penetration, local depot for continuous drug release, and a rate-limiting membrane for modulating systemic absorption of pharmaceuticals via the skin, niosomes, vesicular nanocarriers, are gaining a lot of attention as prospective transdermal drug delivery systems. There are a number of theories put up to explain why niosomes can improve medication transfer through the skin. This review aims to provide an exhaustive collection of recent studies in this fascinating field, with special emphasis on the methods used to maximise the potential of niosomes. Niosomal carriers are suitable for the transdermal delivery of a variety of pharmacological agents, including antioxidant, anticancer, anti-inflammatory, antimicrobial, and antibacterial molecules.