Nanocarrier Drug Delivery Systems Research Articles

Niosomes: A nanocarrier drug delivery system

Novel approaches in the drug delivery system can be used for drug targeting in which the drug gets distributed in the body in such a manner that drug interacts with the target tissue. Niosomes are a type of novel drug delivery system in which the medication is encapsulated in a vesicle. Niosomes are a non-ionic surfactant based multilamellar or unilamellar vesicles in which a fluid arrangement of solute is completely enclosed by a membrane because of the association of surfactant macromolecules as a bilayer. Niosomes release the drug in a controlled manner through its bilayer. Niosomes can be used to carry both the amphiphilic and lipophilic drugs. Niosomes have a great potential in targeted drug delivery of anticancer and anti-infective agents. Niosomes are used to modify the drug release profile, drug absorption, distribution and elimination for the benefit of improving product efficacy and safety and improving patient convenience and compliance. They are very small and microscopic. Although they are structurally similar to liposomes, they offer several advantages over them. Niosomes are stable, less toxic and less expensive than liposomes. This review article represents the structure of Niosomes, its advantages and disadvantages, applications, method of preparation, and characterization techniques of Niosomes.

Niosomes: A nanocarrier drug delivery system

Niosomes: A nanocarrier drug delivery system

Recent advances in access to overcome cancer drug resistance by nanocarrier drug delivery system.

Cancer is currently one of the most intractable diseases causing human death. Although the prognosis of tumor patients has been improved to a certain extent through various modern treatment methods, multidrug resistance (MDR) of tumor cells is still a major problem leading to clinical treatment failure. Chemotherapy resistance refers to the resistance of tumor cells and/or tissues to a drug, usually inherent or developed during treatment. Therefore, an urgent need to research the ideal drug delivery system to overcome the shortcoming of traditional chemotherapy. The rapid development of nanotechnology has brought us new enlightenments to solve this problem. The novel nanocarrier provides a considerably effective treatment to overcome the limitations of chemotherapy or other drugs resulting from systemic side effects such as resistance, high toxicity, lack of targeting, and off-target. Herein, we introduce several tumor MDR mechanisms and discuss novel nanoparticle technology applied to surmount cancer drug resistance. Nanomaterials contain liposomes, polymer conjugates, micelles, dendrimers, carbon-based, metal nanoparticles, and nucleotides which can be used to deliver chemotherapeutic drugs, photosensitizers, and small interfering RNA (siRNA). This review aims to elucidate the advantages of nanomedicine in overcoming cancer drug resistance and discuss the latest developments.

Stimuli-responsive nanocarrier delivery systems for Pt-based antitumor complexes: a review.

Platinum-based anticancer drugs play a crucial role in the clinical treatment of various cancers. However, the application of platinum-based drugs is heavily restricted by their severe toxicity and drug resistance/cross resistance. Various drug delivery systems have been developed to overcome these limitations of platinum-based chemotherapy. Stimuli-responsive nanocarrier drug delivery systems as one of the most promising strategies attract more attention. And huge progress in stimuli-responsive nanocarrier delivery systems of platinum-based drugs has been made. In these systems, a variety of triggers including endogenous and extracorporeal stimuli have been employed. Endogenous stimuli mainly include pH-, thermo-, enzyme- and redox-responsive nanocarriers. Extracorporeal stimuli include light-, magnetic field- and ultrasound responsive nanocarriers. In this review, we present the recent advances in stimuli-responsive drug delivery systems with different nanocarriers for improving the efficacy and reducing the side effects of platinum-based anticancer drugs.

Implementation of Quality by Design in the Formulation and Development of Nanocarrier-Based Drug Delivery Systems.

Quality by design (QbD) has recently fascinated researchers for utilizing it in various arenas of pharma trends. By overcoming the conventional process, QbD prevents the risk of errors caused by the 'guess and by god approach'. This framework fosters profound knowledge of product and process quality by implying sound science and risk assessment strategies. The virtue of QbD leads to the collaborative contribution to pharmaceutical industrialists and satisfies the regulatory bodies. Additionally, leading to rapid production, saves time and expenditure, tremendous versatility, provides immense knowledge, improves robustness, higher consistency, reduces user's dilemma, decreases certainty of failure, declining inter-batch variation in pharmaceutical development. In this ever-increasing continuous production world, regulatory organizations such as the U.S. Food & Drug Administration and the International Conference on Harmonization recommend Q8 to Q14 guidelines in order to obtain the desired quality product. This review extensively discusses on various approaches of QbD for the pharmaceutical development of nano-carrier drug delivery systems. Additionally, QbD's applications in process and analytical method development techniques are documented.

Non-spherical Polymeric Nanocarriers for Therapeutics: The Effect of Shape on Biological Systems and Drug Delivery Properties.

This review aims to highlight the importance of particle shape in the design of polymeric nanocarriers for drug delivery systems, along with their size, surface chemistry, density, and rigidity. Current manufacturing methods used to obtain non-spherical polymeric nanocarriers such as filomicelles or nanoworms, nanorods and nanodisks, are firstly described. Then, their interactions with biological barriers are presented, including how shape affects nanoparticle clearance, their biodistribution and targeting. Finally, their drug delivery properties and their therapeutic efficacy, both in vitro and in vivo, are discussed and compared with the characteristics of their spherical counterparts.

The effects of the nature of the sterol on the properties and stability of niosome bilayer vesicles

Niosome vesicles as potential nanocarriers for drug delivery systems have been in development since the mid-1980s. These vesicles form by self-assembly of cholesterol and nonionic surfactants in an aqueous phase. The aim of the present molecular dynamics (MD) simulation study is to determine how changes in the sterol side chain and ring affect the structure and stability of sorbitan monostearate (Span60) niosome bilayers. Five sterols are examined: cholesterol (CHL), β-sitosterol (BST), ergosterol (ERG), stigmasterol (STS), and lanosterol (LST). Different sets of simulations were performed by varying the number of molecules (30, 40, and 50 % sterol concentration). The interactions between Span60 and the different sterols are found to be strongly dependent on the sterol’s side chain and head group. BST is found to markedly reduce the effectiveness of the sterol on the ordering of the bilayers, a result that persists over the whole range of concentrations examined in this work.

Amphiphilic Block Copolymers: Their Structures, and Self-Assembly to Polymeric Micelles and Polymersomes as Drug Delivery Vehicles.

Self-assembly of amphiphilic block copolymers display a multiplicity of nanoscale periodic patterns proposed as a dominant tool for the 'bottom-up' fabrication of nanomaterials with different levels of ordering. The present review article focuses on the recent updates to the self-association of amphiphilic block copolymers in aqueous media into varied core-shell morphologies. We briefly describe the block copolymers, their types, microdomain formation in bulk and micellization in selective solvents. We also discuss the characteristic features of block copolymers nanoaggregates viz., polymer micelles (PMs) and polymersomes. Amphiphilic block copolymers (with a variety of hydrophobic blocks and hydrophilic blocks; often polyethylene oxide) self-assemble in water to micelles/niosomes similar to conventional nonionic surfactants with high drug loading capacity. Double hydrophilic block copolymers (DHBCs) made of neutral block-neutral block or neutral block-charged block can transform one block to become hydrophobic under the influence of a stimulus (physical/chemical/biological), and thus induced amphiphilicity and display self-assembly are discussed. Different kinds of polymer micelles (viz. shell and core-cross-linked, core-shell-corona, schizophrenic, crew cut, Janus) are presented in detail. Updates on polymerization-induced self-assembly (PISA) and crystallization-driven self-assembly (CDSA) are also provided. Polyion complexes (PICs) and polyion complex micelles (PICMs) are discussed. Applications of these block copolymeric micelles and polymersomes as nanocarriers in drug delivery systems are described.

First-principles studies on two-dimensional aluminum carbide as potential nanocarriers for drug delivery systems

• C 3 Al nanosheet is studied as drug delivery system for anticancer drugs. • The solvation energy reveals the solubility of the studied drug in the aqueous medium. • The highest change in dipole moment of NU after adsorption indicates its high hydrophilicity. • C 3 Al nanosheet can be suitable nanocarrier for the drug delivery of NU. In comparison to conventional macro systems, two-dimensional (2D) sheet-like materials, such as aluminum carbide (C 3 Al), are superior drug delivery systems (DDSs) because of their bioavailability and adsorption. The bioavailability and absorption of most drug molecules can be improved by the surface of 2D materials with an average adsorption energy. Hence, the possibility of using 2D C 3 Al for the drug delivery of nitrosourea (NU) was investigated. Based on the adsorption energy (E ads ) analysis, the NU molecules had an interaction with C 3 Al with a medium interaction energy that is a prerequisite for a suitable DDS. The adsorption energies in NU@C 3 Al were approximately − 21.81 and −11.14 kcal/mol for different complexes. At the end of NU adsorption, the dipole moment (μ) of the surface was enhanced, which facilitated solubility and was essential for the delivery of drugs in living systems. The HOMO-LUMO energy gap of C 3 Al reduced from 3.45 eV to 2.69 eV after the adsorption of NU. According to all computational findings, C 3 Al seems to be a suitable candidate for the delivery of the anticancer drug NU. This research provides useful insights into the development of an experimental C 3 Al-based drug delivery system for NU.

Tailoring the multi-functional properties of phospholipids for simple to complex self-assemblies.

The unique interfacial properties, huge diversity, and biocompatible nature of phospholipids make them an attractive pharmaceutical excipient. The amphiphilic nature of these molecules offers them the property to self-assemble into distinct structures. The solubility, chemical and structural properties, surface charge, and critical packing parameters of phospholipids play an essential role during formulation design. This review focuses on the relationship between the structural features of a phospholipid molecule and the formation of different lipid-based nanocarrier drug delivery systems. This provides a rationale and guideline for the selection of appropriate phospholipids while designing a drug delivery system. Finally, we refer to relevant recent case studies covering different types of phospholipid-based systems including simple to complex assemblies. Different carriers in the size range of 50nm to a few microns can be prepared using phospholipids. The carriers can be delivered through oral, intravenous, nasal, dermal, transmucosal, and subcutaneous routes. A wide range of applicability can be achieved by incorporating various hydrophilic and lipophilic additives in the phospholipid bilayer. Advanced research has led to the discovery of phospholipid complexes and cell membrane mimicking lipids. Overall, phospholipids remain a versatile pharmaceutical excipient for drug delivery. They play multiple roles as solubilizer, emulsifier, surfactant, permeation enhancer, coating agent, release modifier, and liposome former.

Nanocarriers for drug-delivery systems using a ureido-derivatized polymer gatekeeper for temperature-controlled spatiotemporal on-off drug release.

Accidental chemotherapy extravasation exacerbates the side effects of anticancer drugs. Therefore, drug-delivery nanocarriers should be designed to avoid persistent drug release at off-target sites and promote burst drug release at on-target. Considering these requirements, poly(allylamine)-co-poly(allylurea) (PAU), a ureido-derivatized temperature responsive polymer with upper critical solution temperature (UCSTs), is an ideal material. This report describes the fabrication, characterization, and in vitro cellular toxicity of PAU polymer-grafted magnetic mesoporous silica nanoparticles as drug-delivery nanocarriers. A UCST of 43°C and an ultranarrow transition temperature range of 39-43°C was realized, ensuring that the nanocarriers suppressed undesirable leakage to below 10% of the drug loading for 8h in the absence of a thermal stimulus. A drug release burst of up to 75% of the drug loading was achieved within 30min after the stimulus, reducing the viability of the in vitro cancer cells to 12%. Therefore, the ureido-derivatized polymer is one of the most suitable gatekeepers for drug-delivery nanocarriers.

Two-Dimensional Metal-Organic Framework-Based Cellular Scaffolds with High Protein Adsorption, Retention, and Replenishment Capabilities.

Metal-organic frameworks (MOFs) are porous materials with adsorption, storage, and separation capabilities due to their high specific surface areas and large pore volumes. MOFs are thus used in biomedical applications, and MOF nanoparticles have been widely studied as nanocarriers for drug delivery systems. Several research groups recently reported that specific MOF nanoparticles can adsorb and retain proteins, suggesting to us that MOF nanoparticles may have advantages as novel cell culture scaffolds. However, MOF nanoparticles cannot be used as two-dimensional scaffolds for cells. We therefore established a bottom-up technique to construct two-dimensional MOFs [MIL-53 (Al)] on polymer films. The developed two-dimensional MIL-53 (Al) film [fMIL-53 (Al)] exhibited high serum protein adsorption, retention, and replenishment capabilities as compared to conventional cell culture scaffolds. β-Galactosidase, used as a model protein, adsorbed on fMIL-53 (Al) exhibited original enzymatic activity, indicating that proteins are not denatured during the adsorption process. The viability of mouse myoblast cells (C2C12) cultured on fMIL-53 (Al) was 100%, indicating the cell compatibility of fMIL-53 (Al). Importantly, C2C12 cells cultured on serum protein-preadsorbed fMIL-53 (Al) exhibited excellent long-term adhesion, morphology, and proliferation even in a medium lacking serum proteins, demonstrating an important advantage of fMIL-53 (Al) as a cell culture scaffold, given that conventional cell culture scaffolds typically require a serum-containing medium to support stable cell adhesion and proliferation. To our knowledge, this is the first report regarding the application of MOFs as cell culture scaffolds and will serve as a starting point for studying two- and three-dimensional MOF-based cellular scaffolds for cell culture systems and for in vitro and in vivo tissue engineering.

Synthesis and characterization of amine-functionalized Fe3O4/Mesoporous Silica Nanoparticles (MSNs) as potential nanocarriers in drug delivery systems

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have shown great potential for being utilized in Nanocarriers (NCs) applications throughout the Drug Delivery System (DDS). However, there are several obstacles to make a practical magnetic NCs, such as low dispersity and high toxicity in the biological systems, and also low surface area for drug loading. In this work, magnetic NCs have been synthesized through a facile three-step process, first SPIONs were synthesized by the co-precipitation method, then decorated via mesoporous silica and finally the calcinated NCs functionalized with NH2 by a simple process in the ethanol solvent. The structure and morphology of the as-synthesized NCs have been characterized by the usage of different analyzing methods such as XRD, FTIR, TEM, FE-SEM, and TGA. Also, the magnetic properties have been investigated by the means of VSM throughout each step of the procedure. Lastly, we have applied the technique of N2 adsorption-desorption to observe the surface area, pore size, and volume. Besides optimal magnetization of final nanoparticles (30 emu/gr), the as-synthesized NCs claimed the high surface area and small diameter, at 371 m2.g-1 and 70 nm, respectively. Moreover, the functionalized NCs have demonstrated well dispersity over a day in the PBS solution. As a result, the as-prepared nanocarrier able to overcome drug delivery obstacles and used as a potential nanocarrier owing to its small diameter, high surface area/ pore volume, optimal magnetization, and well dispersity in the biological condition.

Lipid-Based Nanocarrier Systems for Drug Delivery: Advances and Applications

Lipid-based nanocarriers have been extensively investigated for drug delivery due to their advantages including biodegradability, biocompatibility, nontoxicity, and nonimmunogenicity. However, the shortcomings of traditional lipid-based nanocarriers such as insufficient targeting, capture by the reticuloendothelial system, and fast elimination limit the efficiency of drug delivery and therapeutic efficacy. Therefore, a series of multifunctional lipid-based nanocarriers have been developed to enhance the accumulation of drugs in the lesion site, aiming for improved diagnosis and treatment of various diseases. In this review, we summarized the advances and applications of lipid-based nanocarriers from traditional to novel functional lipid preparations, including liposomes, stimuli-responsive lipid-based nanocarriers, ionizable lipid nanoparticles, lipid hybrid nanocarriers, as well as biomembrane-camouflaged nanoparticles, and further discussed the challenges and prospects of this system. This exploration may give a complete idea viewing the lipid-based nanocarriers as a promising choice for drug delivery system, and fuel the advancement of pharmaceutical products by materials innovation and nanotechnology.

Comprehensive revision on the nanocarrier drug delivery systems with special reference to artificial intelligence

Nanocarriers outperform traditional medication dosage forms in terms of efficacy, safety, and tolerability because of their small size, large surface area, and potential for precise targeting. More and more researchers are looking to produce nanocarriers that can be used to treat a variety of illnesses. Dendrimers, liposomal nanoparticles, polymersomes, polymer–drug conjugates and peptide nanoparticles are only some of the nanocarriers that have been developed for drug delivery. Other nanocarriers include carbon nanotubes, nanoshells and carbon dioxide nanoparticles. Nanocarriers have been characterised using a variety of approaches during the past few decades, both in vitro and in vivo. Most nanocarriers are characterised using fundamental in vitro, ex vivo, ex situ, and in situ techniques, which emphasise their advantages and limitations as well as regulatory and manufacturing issues that hinder the transfer of nanocarriers from laboratory to clinical use, as described in this review. There is also a discussion of the integration of artificial intelligence with nanotechnology and the advantages and disadvantages of artificial intelligence in the creation and optimization of nanocarriers, along with future prospects.

A mini-review of Nanocarriers in drug delivery systems

The application of nanotechnology indrug delivery systems (DDS) has been researched widely and seen an advancementover the past three decades. Since the 1970s, nanoparticles were primarilyutilised in vaccine deliveries and cancer chemotherapy. In more recent years,they have been found to hold promises for broader applications such as inproteins and therapeutic gene delivery systems. To date, there have been only ahandful of nanocarrier-loaded drugs commercialised into the pharmaceuticalmarket. More research is thus needed to facilitate a breakthrough of theseproducts into the current market. This mini-review mainly focuses on four typesof commonly utilised organic nanocarriers including micelles, compactpolymerics, solid-lipid nanoparticles and liposomal vesicles and discusses theprogress and some challenges associated with these nanoparticles (NP). 

Nanocarrier Drug Delivery Systems: Characterization, Limitations, Future Perspectives and Implementation of Artificial Intelligence.

There has been an increasing demand for the development of nanocarriers targeting multiple diseases with a broad range of properties. Due to their tiny size, giant surface area and feasible targetability, nanocarriers have optimized efficacy, decreased side effects and improved stability over conventional drug dosage forms. There are diverse types of nanocarriers that have been synthesized for drug delivery, including dendrimers, liposomes, solid lipid nanoparticles, polymersomes, polymer–drug conjugates, polymeric nanoparticles, peptide nanoparticles, micelles, nanoemulsions, nanospheres, nanocapsules, nanoshells, carbon nanotubes and gold nanoparticles, etc. Several characterization techniques have been proposed and used over the past few decades to control and predict the behavior of nanocarriers both in vitro and in vivo. In this review, we describe some fundamental in vitro, ex vivo, in situ and in vivo characterization methods for most nanocarriers, emphasizing their advantages and limitations, as well as the safety, regulatory and manufacturing aspects that hinder the transfer of nanocarriers from the laboratory to the clinic. Moreover, integration of artificial intelligence with nanotechnology, as well as the advantages and problems of artificial intelligence in the development and optimization of nanocarriers, are also discussed, along with future perspectives.

Theoretical study of encapsulation of diethylstilbestrol drug into the inner surface of BNNT toward designing a new nanocarrier for drug delivery systems

In this research, the encapsulation and intermolecular non-bonded interactions of an anticancer drug, Diethylstilbestrol (DES), into the inner surfaces of BNNT (8,8–12) were investigated. All Density Functional Theory (DFT) calculations were performed in a gas phase. So, this research focuses on intermolecular hydrogen bonding, van der Waals and steric interactions between active sites of the BNNT and DES by quantum theory of atom in molecule (QTAIM) theory. QTAIM and non-covalent interaction index (NCI) analyses showed the interactions between the DES drug and the BNNT nanotube. The HOMO-LUMO orbitals, Density of States (DOS) plots, and reduced density gradient (RDG) analyses were carried out to determine the effect of DES adsorption into the nanotube. Furthermore, the effect of the abovementioned interactions between the DES and BNNT (8,8–12) on the electronic characteristics, and natural charges have also been estimated. Based on the results, the thermodynamic parameters of BNNT (8,8-12)/DES are in very close agreement with the NCI analysis and showed that the BNNT (8,8–12) adsorb DES via a physisorption process rather than chemical one and the sorption procedure was exothermic in benign and thermodynamically favorable. Therefore, the use of BNNT (8,8–12) as a carrier for DES drug has been confirmed theoretically.

P(OEGMA‐co‐LMA) hyperbranched amphiphilic copolymers as self‐assembled nanocarriers

AbstractWe report on the synthesis of novel amphiphilic hyperbranched copolymers, namely Hyperbranched‐[poly (ethylene glycol) methyl ether methacrylate‐co‐lauryl methacrylate] (H‐[P(OEGMA‐co‐LMA)]), obtained by reversible addition‐fragmentation chain transfer (RAFT) polymerization utilizing the divinyl monomer, ethylene glycol dimethacrylate (EGDMA) as the branching agent. Molecular characterization by size exclusion chromatography (SEC) and proton nuclear magnetic resonance (1H‐NMR) spectroscopy indicated the success of the polymerization. The self‐assembly behavior in aqueous media was investigated by light scattering techniques and fluorescence spectroscopy. The hyperbranched copolymers form multimolecular aggregates of nanoscale dimensions with a low critical aggregation concentration. In addition, the model hydrophobic drug, curcumin (CUR), known also for its intrinsic fluorescence properties, was used in order to investigate the H‐[P(OEGMA‐co‐LMA)] copolymers drug encapsulation ability. Curcumin is successfully loaded into the polymeric nanoparticles, as confirmed by dynamic light scattering and UV–Vis spectroscopy. Interestingly, curcumin hydrophobic interactions with the hyperbranched copolymers result in more well‐defined co‐assembled nanostructures, in terms of size and size distribution. The mixed copolymer‐CUR nano‐assemblies consist of small size nanoparticles (<100 nm) which exhibit relatively high size uniformity, colloidal stability and fluorescent properties. Overall, results signify that the biocompatible H‐[P(OEGMA‐co‐LMA)] nanostructures could potentially serve as nanocarrier systems for drug delivery and bio‐imaging applications.

Co-Delivery of Dexamethasone and Captopril by α8 Integrin Antibodies Modified Liposome-PLGA Nanoparticle Hybrids for Targeted Anti-Inflammatory/Anti-Fibrosis Therapy of Glomerulonephritis.

PurposeMesangial cells-mediated glomerulonephritis refers to a category of immunologically mediated glomerular injuries characterized by infiltration of circulating inflammatory cells, proliferation of mesangial cells, and the common pathological manifestation to the later stage is renal fibrosis, accompanied by excessive accumulation of extracellular matrix (ECM). Treatment regimens include glucocorticoids and immunosuppressive agents, but their off-target distribution causes severe systemic toxicity. Hence, specific co-delivery of “anti-inflammatory/anti-fibrosis” drugs to the glomerular mesangial cell (MC) region is expected to produce better therapeutic effects.MethodsA novel kidney-targeted nanocarrier drug delivery system targeting MCs was constructed using passive targeting resulting from the difference in pore size between the glomerular endothelial layer and the basement membrane, and active targeting based on the specific binding of antibodies and antigens. Specifically, a liposome-nanoparticle hybrid (PLGA-LNHy) was formed by coating the surface of PLGA nanoparticles (NPs) with a phospholipid bilayer, and then PLGA-LNHy was co-modified with PEG and α8 integrin antibodies to obtain PLGA immunoliposomes (PLGA-ILs).ResultsThe results showed that the obtained NPs had a core-shell structure, uniform and suitable particle size (119.1 ± 2.31 nm), low cytotoxicity, and good mesangial cell-entry ability, which can successfully accumulate in the glomerular MC region. Both dexamethasone (DXMS) and captopril (CAP) were loaded onto PLGA-ILs with a drug loading of 10.22 ± 1.00% for DXMS and 6.37 ± 0.25% for CAP (DXMS/CAP@PLGA-ILs). In vivo pharmacodynamics showed that DXMS/CAP@PLGA-ILs can effectively improve the pathological changes in the mesangial area and positive expression of proliferating cell nuclear antigen (PCNA) in glomeruli as well as reduce the expression of inflammatory factors, fibrotic factors and reactive oxygen species (ROS). Thus, renal inflammation and fibrosis were relieved.ConclusionWe have provided a strategy to increase nanoparticle accumulation in MCs with the potential to implement regulatory effects of anti-inflammatory and anti-fibrosis in glomerulonephritis (GN).