Nanocarrier Drug Delivery Systems Research Articles

GELLAN GUM- AND PECTIN-MAGNETIC GRAPHENE OXIDE NANOCARRIERS LOADED WITH CINNAMALDEHYDE FOR MOSQUITO LARVAE CONTROL

Magnetic nanoparticles have evolved over the last few decades as nanocarriers in drug delivery systems for hydrophobic drugs. Here, novel gellan gum magnetic graphene oxide (GG-GO-Fe3O4) and pectin magnetic graphene oxide (PEC-GO-Fe3O4) nanocomposites were prepared to carry cinnamaldehyde to control Aedes aegypti larvae. Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM) and scanning transmission electron microscopy (STEM) were employed to investigate the physicochemical characteristics of the nanocomposites. Entrapment efficiencies and loading capacities of nanocomposites on cinnamaldehyde were examined using ultraviolet-visible analysis. The successful cinnamaldehyde loading was confirmed by C-C and C-O stretches in the FTIR spectra. Results of in vitro release study showed the capabilities of GG-GO-Fe3O4 as a drug carrier system, extending the cinnamaldehyde release period for 36 h, and the release profiles for both nanocomposites fit the Korsmeyer-Peppas kinetic model with correlation coefficient (R2) values of over 0.9809. The cinnamaldehyde-loaded GG-GO-Fe3O4 nanocomposites induced 68% mortality after 72 h of exposure, with LC50 values ranging from 2.0488 and 15.9121 mg/L. The conjugation of GO-Fe3O4 with biopolymers improved the water solubility of cinnamaldehyde by 36.41 to 62.83 times vs. free cinnamaldehyde in water (1.42 mg/mL). Overall, these results are beneficial for researchers dealing with mosquito control and prevention.

Uptake of surface-functionalized thermo-responsive polymeric nanocarriers in corticospinal tract motor neurons

Nanocarrier drug delivery systems are attractive options for targeted delivery of survival- and regeneration-enhancing therapeutics to neurons damaged by degenerative or traumatic central nervous system (CNS) lesions. Functional groups on nanocarrier surfaces allow derivatization with molecules to target specific cells but may affect cellular interactions and nanocarrier uptake. We synthesized differently sized –COOH and –NH2 surface functionalized polymeric nanocarriers (SFNCs) by emulsion copolymerization and assessed uptake by different cell types in mixed cortical cultures. Following 60-min incubation with SFNCs, mean intensity measurements of fluorescently labeled SFNCs indicated that corticospinal tract motor neurons (CSMNs) took up more COOH- or NH2- functionalized SFNCs with similar sizes (150 nm), compared to glia. However, larger diameter (750 nm) SFNCs were taken up at higher concentrations compared to smaller COOH-derivatized SFNCs (150 nm). These data suggest that larger SFNCs may provide an advantage for enhanced uptake by targeted neurons.

Nanocarrier drug delivery system: promising platform for targeted depression therapy.

Depression is a chronic mental disorder characterized by persistent low mood and loss of interest. Treatments for depression are varied but may not be sufficient cure. Drug-based treatment regimens have drawbacks such as slow onset of action, low bioavailability, and drug side effects. Nanocarrier Drug Delivery Systems (NDDS) has received increasing attention for brain drug delivery since it assists the drug through the blood-brain barrier and improves bioavailability, which may be beneficial for treating depression. Due to the particle size and physicochemical properties of nanocarriers, it presents a promise to improve the stability and solubility of antidepressants, thereby enhancing the drug concentration. Moreover, ligand-modified nanocarriers can be taken as a target direct medicines release system and reduce drug side effects. The purpose of the present review is to provide an up-to-date understanding of the Nanocarrier drug delivery system and relevant antidepressants in different routes of ingestion, to lay a foundation for the treatment of patients with depression.

Photodynamic therapy using polymeric micelles containing photosensitizers

In recent years, photodynamic therapy (PDT) has emerged as a promising cancer treatment due to its minimal risk of harming normal cells and non-invasive nature, alleviating the burden on patients. PDT utilizes light and photosensitizers to exploit photochemical reactions for therapeutic purposes. However, a challenge arises post-PDT treatment, where residual photosensitizers in the body can induce phototoxicity upon exposure to sunlight.To address this issue, the concept of drug delivery systems (DDS) has garnered attention. DDS aims to control drug distribution in the body, maximizing therapeutic effects while minimizing side effects. In this study, we explore the use of polymeric micelles as nanocarriers for DDS, leveraging their advantages such as tumor-specific accumulation and low toxicity.The synthesis of photosensitizer-containing block copolymers was conducted, followed by evaluation of micellization using NMR and assessment of phototoxicity utilizing HeLa cells. The obtained results revealed a critical micelle concentration (CMC) of 0.16 mg/mL. Notably, significant cell toxicity was observed at the CMC concentration in the phototoxicity assay, highlighting the potential of these polymeric micelles as an effective nanocarrier system for enhanced photodynamic therapy.

Druggability, molecular targets, and nanocarrier delivery of natural triterpenoid celastrol against chronic diseases

Celastrol is an active compound from the root of Tripterygium wilfordii Hook F that shows great potential in the treatment of inflammation, cancer, neurodegeneration, diabetes, and obesity. However, the clinical application of celastrol has been hindered by its low bioavailability and severe systemic toxicity. The aim of this review was to discuss the druggability, molecular targets, and nanocarrier delivery of the natural triterpenoid, celastrol, against chronic diseases. We sequentially investigated the physicochemical properties of celastrol using online tools (pkCSM and SwissADME), reviewed the recent studies on the molecular mechanisms underlying the therapeutic effects of celastrol, and examined the potential of nanoparticle-mediated delivery systems for safe and effective delivery of celastrol. The cancer-related targets and pathways involved were further predicted through network pharmacologic analysis. This review provides molecular insights into the pharmacologic activities and molecular mechanisms underlying celastrol, as well as useful information for the selection of nanocarrier drug delivery system for the clinical delivery of celastrol against various chronic diseases.

ROS-responsive polymeric micelles with aggregation-induced emission effects for drug delivery and cellular imaging

The ROS-responsive amphiphilic copolymer micelles mPEG-TK-PCL-TPE, combined with AIE properties, enable real-time drug release monitoring and intracellular tracing, and ensures stable circulation and rapid release in tumors.

Theoretical investigations on modeling blood flow through vessel for understanding effectiveness of magnetic nanocarrier drug delivery systems.

For cancer therapy, the focus is now on targeting the chemotherapy drugs to cancer cells without damaging other normal cells. The new materials based on bio-compatible magnetic carriers would be useful for targeted cancer therapy, however understanding their effectiveness should be done. This paper presents a comprehensive analysis of a dataset containing variables x(m), y(m), and U(m/s), where U represents velocity of blood through vessel containing ferrofluid. The effect of external magnetic field on the fluid flow is investigated using a hybrid modeling. The primary aim of this research endeavor was to construct precise and dependable predictive models for velocity, utilizing the provided input variables. Several base models, including K-nearest neighbors (KNN), decision tree (DT), and multilayer perceptron (MLP), were trained and evaluated. Additionally, an ensemble model called AdaBoost was implemented to further enhance the predictive performance. The hyper-parameter optimization technique, specifically the BAT optimization algorithm, was employed to fine-tune the models. The results obtained from the experiments demonstrated the effectiveness of the proposed approach. The combination of the AdaBoost algorithm and the decision tree model yielded a highly impressive score of 0.99783 in terms of R2, indicating a strong predictive performance. Additionally, the model exhibited a low error rate, as evidenced by the root mean square error (RMSE) of 5.2893 × 10-3. Similarly, the AdaBoost-KNN model exhibited a high score of 0.98524 using R2 metric, with an RMSE of 1.3291 × 10-2. Furthermore, the AdaBoost-MLP model obtained a satisfactory R2 score of 0.99603, accompanied by an RMSE of 7.1369 × 10-3.

Different Approaches for Transdermal Nano-Carrier Delivery System

Transdermal drug delivery is a validated technology that makes a significant contribution to global pharmaceutical care. Since 1980, the sector has seen impressive growth with several commercial successes. The term transdermal drug delivery refers to the delivery of a drug across the layers of skin with the intention of allowing the drug to be absorbed through the skin in a predetermined and controlled rate manner. Skin is one of the largest organs that act as an efficient barrier for drug delivery. The present study focuses on the different approaches of nano-carrier system that delivers the nano-carrier drug across the skin barrier with the help of transdermal delivery system. Nano-carrier drug delivery systems are one of the biggest challenges to deliver drug into systemic circulation by crossing the skin barrier providing a passive drug delivery strategy that is known to be safer and faster than the conventional method. In this review, we describe the diverse types of nano-carriers approaches that have been synthesized for transdermal delivery system includes liposomes, niosomes, ethosomes, solid lipid nanoparticles (SLN), nanostructured lipid carrier (NLC), polymeric nanoparticles, nanocrystals, nanofibers and nanosuspension/nanoemulsion. Several characterization methods of transdermal delivery system have been proposed to control the behavior of nano-carriers, along with in-vitro and in-vivo and other evaluation parameters. It was concluded that the compatibility of nano-carriers with the skin structure should be considered for transdermal nanocarrier delivery systems, which will be the most preferred route for drug delivery in the future as it offers high patient compliance, controlled dosing, low frequency of dosing, high physico-chemical stability and better dermal bioavailability, etc.

Prospects of plant-derived exosome-like nanocarriers in oncology and tissue engineering.

Almost all cell types, either in vivo or in vitro, create extracellular vesicles (EVs). Among them are exosomes (EXOs), i.e., tiny nanovesicles containing a lipid bilayer, proteins, and RNAs that are actively involved in cellular communication, indicating that they may be exploited as both diagnostics and therapeutics for conditions like cancer. These nanoparticles can also be used as nanocarriers in many types of research to carry agents such as drugs. Plant-derived exosome-like nanoparticles (PENs) are currently under investigation as a substitute for EXOs formed from mammalian cells, allowing researchers to get beyond the technical constraints of mammalian vesicles. Because of their physiological, chemical, and biological properties, PENs have a lot of promise for use as nanocarriers in drug delivery systems that can deliver various dosages, especially when it comes to large-scale repeatability. The present study has looked at the origins and isolation techniques of PENs, their anticancer properties, their usage as nanocarriers in the treatment of different illnesses, and their antioxidant properties. These nanoparticles can aid in the achievement of therapeutic objectives, as they have benign, non-immunogenic side effects and can pass biological barriers. Time-consuming and perhaps damaging PEN separation techniques is used. For the current PEN separation techniques to be used in commercial and therapeutic settings, they must be altered. In this regard, the concurrent application of biological sciences can be beneficial for improving PEN separation techniques. PENs' innate metabolic properties provide them a great deal of promise for application in drug delivery systems. However, there could be a risk to both the loaded medications and the intrinsic bioactive components if these particles are heavily armed with drugs. Therefore, to prevent these side effects, more studies are needed to devise sophisticated drug-loading procedures and to learn more about the physiology of PENs.

Nanocarrier‐Based Drug Delivery Systems using Microfluidic‐Assisted Techniques

Nanocarrier‐mediated drug delivery in life science and patient care is now highly recognized and has gained significant traction in pharmaceuticals for clinical applications. Besides, the incorporation of microfluidic technology for the synthesizing and delivery of nanocarriers facilitates preclinical drug testing under biomimicking physiological conditions, which further increases the prospect of nanocarrier drug delivery systems in clinical use. Indeed, an inherent amenability of microfluidics shows fine‐tuned manipulation and controlled release of nanocarrier drugs in a spatiotemporal manner. The progress of microfluidic‐assisted potential drug delivery platforms is reviewed and summarized with a focus on factors determining the design of novel nanodrug delivery microfluidic systems, on‐chip functionalization and synthesis mechanisms of nanodrugs, and stimulation‐responsive and organ‐specific drug delivery platforms, including different challenges associated with developing platforms in benchtop research that hinder platforms’ clinical translation. Moreover, the commercial scenario and prospects of the microfluidic nanodrug delivery platforms are evaluated, and further predictive suggestions are provided for developing multitargeting microfluidic/organ‐on‐a‐chip nanodrug delivery platforms and overcoming the challenges associated with commercialization. This review recognizes that although numerous reports have reinforced the promise of microfluidic nanodrug delivery platforms, much remains to be done in lab and benchtop works to realize it in clinical practice through commercialization.

Active Transport and Ocular Distribution of Intravitreally Injected Liposomes.

Drug delivery to the retina remains a challenge due to ocular barriers and fast clearing mechanisms. Nanocarrier drug delivery systems (NDDSs) hold the promise of prolonging intraocular retention times and increasing drug concentrations in the retina. Anionic and cationic PEGylated liposomes, loaded with oxaliplatin (OxPt) to be used as trace element, were prepared from dry lipid powders. The differently charged liposomes were intravitreally injected in C57BL/6JrJ mice; eyes were harvested 2hours and 24hours post-injection. To investigate active transport mechanisms in the eye, a subset of mice were pre-injected with chloroquine before injection with cationic liposomes. Eyes were dissected and the distribution of OxPt in different tissues were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Both liposome formulations enhanced the retention time of OxPt in the vitreous over free OxPt. Surprisingly, when formulated in cationic liposomes, OxPt translocated through the retina and accumulated in the RPE-sclera. Pre-injection with chloroquine inhibited the transport of liposomal OxPt from the vitreous to the RPE-sclera. We show that liposomes can enhance the retention time of small molecular drugs in the vitreous and that active transport mechanisms are involved in the trans retinal transport of NDDS after intravitreal injections. These results highlight the need for understanding the dynamics of ocular transport mechanisms in living eyes when designing NDDS with the back of the eye as the target. Active transport of nanocarriers through the retina will limit the drug concentration in the neuronal retina but might be exploited for targeting the RPE.

New cage-based imine and ester linked COF as a smart nanocarrier drug delivery system

New cage-based imine and ester linked COF as a smart nanocarrier drug delivery system

PEGylated bottom-up synthesized graphene nanoribbons loaded with camptothecin as potential drug carriers

This work discusses the potential use of bottom-up synthesized graphene nanoribbons (GNRs) as nano-carriers for drug delivery systems (DDSs). GNRs have a high loading capacity for anticancer drugs due to their high specific surface area and non-covalent adsorption with hydrophobic anticancer drug molecules. Herein, we synthesized GNRs using a bottom-up approach, modified with PEG2000 (GNR-PEG) and PEG2000 carrying folic acid chains (GNR-PEG-FA), and then loaded with camptothecin (CPT). The targeting ability mediated by folic acid of the GNR derivative was evaluated using cellular assays, and the cytotoxicity of GNR systems loaded with CPT was assessed by in vitro studies. They suggest that the functionalization of GNR derivatives with folic acid significantly affects their interaction with cells expressing different levels of folic acid receptors. The authors also explore the possibility to employ GNRs in photothermal therapy (PTT). GNR-PEG and GNR-PEG-FA display minor or no toxicity in standard cell cultures, but they show remarkable thermal response upon NIR irradiation, causing complete loss of cell viability within a few hours of treatment. This work highlights the potential of GNRs as DDSs and emphasizes the importance of further research on their biocompatibility and as a platform for PTT.

Rational Design and Multicomponent Synthesis of Lipid-Peptoid Nanocomposites towards a Customized Drug Delivery System Assembly.

Nanotechnology has assumed a significant role over the last decade in the development of various technologies applied to health sciences. This becomes even more evident with its application in controlled drug delivery systems. In this context, peptoids are a promising class of compounds for application as nanocarriers in drug delivery systems. These compounds can be obtained efficiently and with highly functionalized structural diversity via the Ugi 4-component reaction (U-4CR). Herein, we report the design of the process control strategy for the future development of lipid-peptoid-based customized drug delivery system assemblies. Over 20 lipid-peptoid nanocomposites were synthesized via the U-4CR in good to excellent yields. These products were successfully submitted to the nanoparticle formation by the emulsification-evaporation process from lipophilic solution and analyzed via Dynamic Light Scattering (DLS). Several molecules generated nanoparticles with a size ≤200 nm, making them good candidates for drug delivery systems, such as in cancer treatment.

Carbon quantum dots-based fluorescent layered double hydroxide for targeted drug delivery application

Layered double hydroxides (LDHs) are a class of layered materials that have received great attention as drug delivery carriers due to their excellent properties such as biocompatibility, chemical stability, easy synthesis, anion exchange capacity, and controlled drug release. In this research, LDH nanosheets based on Ca and Al were synthesized by a coprecipitation method. The LDH nanosheets were in situ coated by polyethylene glycol (PEG). The LDH nanosheets were decorated with carbon quantum dots (CQDs) derived from citric acid by a hydrothermal method and targeted with folic acid. Doxorubicin hydrochloride (DOX) was used as a model drug to investigate the drug loading and release of the fluorescent LDH. XRD analysis showed that the content of PEG in the synthesis medium affects the crystallinity of the LDHs. FTIR analysis confirmed the successful attachment of CQDs and folic acid (FA) on LDH nanosheets. The fluorescence of the synthesized nanohybrid was influenced by the CQDs content. UV–Vis spectroscopy showed the DOX can be loaded on the nanohybrid with a loading efficiency of 32 %. The drug release of the nanohybrid is pH-dependent. The drug can be released up to 83 % within 12 h in the acidic environment while the release reaches 63 % in the physiological pH at the same time. The synthesized CQDs can be used as pH-dependent fluorescent and targeted nanocarriers in drug delivery systems.

Responsive nanosystems for targeted therapy of ulcerative colitis: Current practices and future perspectives

The pharmacological approach to treating gastrointestinal diseases is suffering from various challenges. Among such gastrointestinal diseases, ulcerative colitis manifests inflammation at the colon site specifically. Patients suffering from ulcerative colitis notably exhibit thin mucus layers that offer increased permeability for the attacking pathogens. In the majority of ulcerative colitis patients, the conventional treatment options fail in controlling the symptoms of the disease leading to distressing effects on the quality of life. Such a scenario is due to the failure of conventional therapies to target the loaded moiety into specific diseased sites in the colon. Targeted carriers are needed to address this issue and enhance the drug effects. Conventional nanocarriers are mostly readily cleared and have nonspecific targeting. To accumulate the desired concentration of the therapeutic candidates at the inflamed area of the colon, smart nanomaterials with responsive nature have been explored recently that include pH responsive, reactive oxygen species responsive (ROS), enzyme responsive and thermo – responsive smart nanocarrier systems. The formulation of such responsive smart nanocarriers from nanotechnology scaffolds has resulted in the selective release of therapeutic drugs, avoiding systemic absorption and limiting the undesired delivery of targeting drugs into healthy tissues. Recent advancements in the field of responsive nanocarrier systems have resulted in the fabrication of multi-responsive systems i.e. dual responsive nanocarriers and derivitization that has increased the biological tissues and smart nanocarrier’s interaction. In addition, it has also led to efficient targeting and significant cellular uptake of the therapeutic moieties. Herein, we have highlighted the latest status of the responsive nanocarrier drug delivery system, its applications for on–demand delivery of drug candidates for ulcerative colitis, and the prospects are underpinned.

Unraveling the in vivo biological fate of mPEG2000-PDLLA2500-COOH diblock copolymers by LC-MS/MS based on CID in source technique

Methoxy poly (ethylene glycol)-poly(D, L-lactic acid) (mPEG-PDLLA) is a biocompatible and amphiphilic diblock copolymer composed of a hydrophilic poly(ethylene glycol) block and a hydrophobic poly(D, L-lactic acid) block, which can self-assemble into micelles in aqueous solution. It is one of the most widely used diblock copolymers for drug delivery, drug solubilization and drug encapsulation. Fully characterizing the in vivo fate of mPEG-PDLLA diblock copolymers is important to promote the further development of polymer-based nanocarrier drug delivery systems. However, to date, a bioanalysis assay for simultaneous quantification of mPEG-PDLLA and mPEG has not been reported. In this study, we developed such a novel LC-MS/MS assay based on CID in source technique and used it to study the multiple-dose pharmacokinetic, tissue distribution and excretion of mPEG2000-PDLLA2500-COOH and mPEG2000 in rat after intravenous administration. The results indicate that mPEG2000-PDLLA2500-COOH and mPEG2000 are mainly distributed to the liver, lung, spleen and kidney after intravenous administration. mPEG2000-PDLLA2500-COOH is mostly excreted via the renal route in the form of mPEG2000. Overall, the results of this study provide a comprehensive and clear picture of the in vivo fate of mPEG2000-PDLLA2500-COOH which will be useful in evaluating the efficiency and safety of polymer-based nanocarrier drug delivery systems.

Controlled Delivery of Amoxicillin and Rifampicin by Three‐Dimensional Polyvinyl alcohol/Bismuth Ferrite Scaffolds

AbstractSkin is a protective barrier that can protect against environmental influences and renew itself. However, in some cases, this regenerative property is lost, and this causes delays in wound healing. Wound healing is a complex and long‐lasting phase. Any bacterial infection during the wound healing process delays wound healing. The therapeutic efficacy can be increased by using nanocarrier drug delivery systems to the target tissue with modern wound dressings. Controlled nano drug delivery systems increase the therapeutic efficacy in the treatment of diseases and provide a faster recovery process. In this study, amoxicillin (AMX) and rifampicin (RIF) were loaded into the bismuth ferrite (BFO) particles which were synthesized with the co‐precipitation method. Then, these drug‐loaded BFO particles (0.075 %) were added separately to 13 % polyvinyl alcohol (PVA) solution and the solutions were printed three‐dimensionally to obtain three dimensional scaffolds. With these designed scaffolds, it is aimed to reduce the risk of inflammation in wound tissues and increase therapeutic efficacy with controlled release. The SEM images proved that homogeneous pore distributions could be achieved with these combinations. The tensile test results showed that drug‐loaded BFO addition increased the mechanical strength of the 13 % PVA scaffold. The biocompatibility test results demonstrated that the highest viability values of the human adipose tissue‐derived mesenchymal stem cells were obtained for AMX‐added 13 % PVA scaffolds.

Solid Lipid Nanoparticles (SLNs): Advancements in Modification Strategies Toward Drug Delivery Vehicle.

Solid lipid nanoparticles are at the cornerstone of the swiftly growing area of medical nanotechnology, having several potential functions in drug delivery, research, clinical care, and a variety of other fields. They provide the opportunity of developing novel therapies due to their unique properties, such as small particle size and being prepared from physiological biodegradable lipids. The loading of bioactive molecules into nanocarriers is a novel drug delivery prototype employed for various drug targeting levels. Hence, SLNs hold a great promise for achieving the aim of targeted and controlled drug delivery. For this reason, they have attracted the extensive attention of scientists and researchers. This review is based on recent studies and research, and here we present advantages, disadvantages, and preparation methods, several advanced modifications, targeting strategies, and recent applications of solid lipid nanocarriers in drug delivery systems.

A detailed insight of the tumor targeting using nanocarrier drug delivery system

Human struggle against the deadly disease conditions is continued since ages. The contribution of science and technology in fighting against these diseases cannot be ignored exclusively due to the invention of novel procedure and products, extending their size ranges from micro to nano. Recently nanotechnology has been gaining more consideration for its ability to diagnose and treat different cancers. Different nanoparticles have been used to evade the issues related with conservative anticancer delivery systems, including their nonspecificity, adverse effects and burst release. These nanocarriers including, solid lipid nanoparticles (SLNs), liposomes, nano lipid carriers (NLCs), nano micelles, nanocomposites, polymeric and magnetic nanocarriers, have brought revolutions in antitumor drug delivery. Nanocarriers improved the therapeutic efficacy of anticancer drugs with better accumulation at the specific site with sustained release, improved bioavailability and apoptosis of the cancer cells while bypassing the normal cells. In this review, the cancer targeting techniques and surface modification on nanoparticles are discussed briefly with possible challenges and opportunities. It can be concluded that understanding the role of nanomedicine in tumor treatment is significant, and therefore, the modern progressions in this arena is essential to be considered for a prosperous today and an affluent future of tumor patients.