Nanoscale Drug Delivery Systems Research Articles

Cisplatin-encapsulated TRAIL-engineered exosomes from human chorion-derived MSCs for targeted cervical cancer therapy

BackgroundCisplatin (DDP) is an efficacious and widely applied chemotherapeutic drug for cervical cancer patients who are diagnosed as metastatic and inoperable, or desiring fertility preservation. Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) selectively triggers cancer cells apoptosis by binding to cognate death receptors (DR4 and DR5). Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been regarded as ideal drug carriers on account of their nanoscale, low toxicity, low immunogenicity, high stability, biodegradability, and abundant sources.MethodsHuman chorion-derived mesenchymal stem cells (hCD-MSCs) were isolated by adherent culture method. TRAIL-engineered hCD-MSCs (hCD-MSCsTRAIL) were constructed by lentivirus transfection, and its secreted Exo (hCD-MSCs-ExoTRAIL) were acquired by differential centrifugation and confirmed to overexpress TRAIL by western blotting. Next, nanoscale drug delivery systems (DDP & hCD-MSCs-ExoTRAIL) were fabricated by loading DDP into hCD-MSCs-ExoTRAIL via electroporation. The CCK-8 assay and flow cytometry were conducted to explore the proliferation and apoptosis of cervical cancer cells (SiHa and HeLa), respectively. Cervical cancer-bearing nude mice were constructed to examine the antitumor activity and biosafety of DDP & hCD-MSCs-ExoTRAIL in vivo.ResultsCompared with hCD-MSCs-Exo, hCD-MSCs-ExoTRAIL weakened proliferation and enhanced apoptosis of cervical cancer cells. DDP & hCD-MSCs-ExoTRAIL were proved to retard cervical cancer cell proliferation and propel cell apoptosis more effectively than DDP or hCD-MSCs-ExoTRAIL alone in vitro. In cervical cancer-bearing mice, DDP & hCD-MSCs-ExoTRAIL evidently hampered tumor growth, and its role in inducing apoptosis was mechanistically associated with JNK/p-c-Jun activation and survivin suppression. Moreover, DDP & hCD-MSCs-ExoTRAIL showed favorable biosafety in vivo.ConclusionsDDP & hCD-MSCs-ExoTRAIL nanoparticles exhibited great promise for cervical cancer treatment as an Exo-based chemo-gene combinational therapy in clinical practice.Graphical abstract

Recent Advances in Cyclodextrin-Based Nanoscale Drug Delivery Systems.

Cyclodextrins (CDs) belong to a class of cyclic oligosaccharides characterized by their toroidal shape consisting of glucose units linked via α-1,4-glycosidic bonds. This distinctive toroidal shape exhibits a dual nature, comprising a hydrophobic interior and a hydrophilic exterior, making CDs highly versatile in various pharmaceutical products. They serve multiple roles: they act as solubilizers, stabilizers, controlled release promoters, enhancers of drug bioavailability, and effective means of masking undesirable tastes and odors. Taking advantage of these inherent benefits, CDs have been integrated into numerous nanoscale drug delivery systems. The resulting nanomaterials exploit the exceptional properties of CDs, including their ability to solubilize hydrophobic drugs for substantial drug loading, engage in supramolecular complexation for engineered nanomaterials, increase bioavailability for improved therapeutic efficacy, stabilize labile drugs, and exhibit biocompatibility and versatility. This paper compiles recent studies on CD functional nanoscale drug delivery platforms. First, we described the physicochemical and toxicological aspects of CDs, CD/drug inclusion complexation, and their impact on improving drug bioavailability. We then summarized applications for CD-functional nano delivery systems based on polymeric, hybrid, lipid-based nanoparticles, and CD-based nanofibers. Particular interest was in the targeted applications and the function of the CD molecules used. In most applications, CD molecules were used for drug solubilization and loading, while in some studies, CD molecules were employed for supramolecular complexation to construct nanoscale drug delivery systems. Finally, the review concludes with a thoughtful consideration of the current challenges and outlook.

Ellagic acid-enhanced biocompatibility and bioactivity in multilayer core-shell gold nanoparticles for ameliorating myocardial infarction injury

BackgroundMyocardial infarction (MI) is the main contributor to most cardiovascular diseases (CVDs), and the available post-treatment clinical therapeutic options are limited. The development of nanoscale drug delivery systems carrying natural small molecules provides biotherapies that could potentially offer new treatments for reactive oxygen species (ROS)-induced damage in MI. Considering the stability and reduced toxicity of gold-phenolic core-shell nanoparticles, this study aims to develop ellagic acid-functionalized gold nanoparticles (EA-AuNPs) to overcome these limitations.ResultsWe have successfully synthesized EA-AuNPs with enhanced biocompatibility and bioactivity. These core-shell gold nanoparticles exhibit excellent ROS-scavenging activity and high dispersion. The results from a label-free imaging method on optically transparent zebrafish larvae models and micro-CT imaging in mice indicated that EA-AuNPs enable a favorable excretion-based metabolism without overburdening other organs. EA-AuNPs were subsequently applied in cellular oxidative stress models and MI mouse models. We found that they effectively inhibit the expression of apoptosis-related proteins and the elevation of cardiac enzyme activities, thereby ameliorating oxidative stress injuries in MI mice. Further investigations of oxylipin profiles indicated that EA-AuNPs might alleviate myocardial injury by inhibiting ROS-induced oxylipin level alterations, restoring the perturbed anti-inflammatory oxylipins.ConclusionsThese findings collectively emphasized the protective role of EA-AuNPs in myocardial injury, which contributes to the development of innovative gold-phenolic nanoparticles and further advances their potential medical applications.Graphical

Construction of anticancer drug incorporated aptamer-functionalized cationic β-lactoglobulin: induction of cell cycle arrest and apoptosis in colorectal cancer

Nanoscale drug delivery systems that are both multifunctional and targeted have been developed using proteins as a basis, thanks to their attractive biomacromolecule properties. A novel nanocarrier, aptamer (AS1411)-conjugated β-lactoglobulin/poly-l-lysine (BLG/Ap/PL) nanoparticles, was developed in this study. To this unique formulation, the as-prepared nanocarrier blends the distinctive features of an aptamer as a chemotherapeutic targeting agent with those of protein nanocarriers. By loading cabazitaxel (CTX) onto the nanocarriers, the therapeutic potential of BLG/Ap/PL could be demonstrated. The CTX-loaded BLG/Ap/PL (CTX@BLG/Ap/PL) showed a regulated drug release profile in an acidic milieu, which could improve therapeutic efficacy in cancer cells and have a high drug encapsulation efficacy of up to 93%. However, compared to free CTX, CTX@BLG/Ap/PL killed colorectal HCT116 cancer cells with a higher efficacy at 24 and 48 h. Further investigation confirms the apoptosis by acridine orange and ethidium bromide (AO/EB), and DAPI staining confirms the morphological changes, chromatin condensation, and membrane blebbing in the treated cell through flow cytometry displayed the release of higher percentages of apoptosis. Cell cycle analysis revealed that CTX@BLG/Ap/PL induced sub-G1 and G2/M phase (apoptosis) at 24 and 48 h. Annexin V/propidium iodide (PI) flow cytometry analysis confirmed that CTX@BLG/Ap/PL induces apoptosis in HCT116 cells. Overall, this study proved that CTX@BLG/Ap/PL had several advantages over free chemotherapeutic drugs and showed promise as a solution to the clinical problems associated with targeted antitumor drug delivery systems.

Nanomedicine and Targeted Drug Delivery: Advances and Challenges

Nanomedicine, the application of nanotechnology to medicine, has revolutionized the field by providing novel approaches to diagnosing, treating, and preventing diseases. Among its various applications, targeted drug delivery has emerged as a key area of focus, offering the potential to enhance therapeutic efficacy and minimize side effects by directing drugs specifically to diseased cells or tissues. This review discusses the latest advancements in nanomedicine, particularly in the design and development of nanoscale drug delivery systems such as liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles. We explore the mechanisms of passive and active targeting, as well as stimuli-responsive delivery systems. Clinical applications in cancer therapy, cardiovascular diseases, neurological disorders, and infectious diseases are examined to illustrate the practical impact of these technologies. Furthermore, we address the challenges facing the field, including toxicity and biocompatibility concerns, manufacturing and scalability issues, regulatory and ethical considerations, and the integration of personalized medicine approaches. By providing a comprehensive overview of the current state and future directions of nanomedicine and targeted drug delivery, this review aims to highlight the transformative potential of these technologies in improving patient outcomes and advancing healthcare. Keywords: Nanomedicine, Targeted drug delivery, Liposomes, Passive targeting, Personalized medicine

Reverse Gradient Distributions of Drug and Polymer Molecules within Electrospun Core-Shell Nanofibers for Sustained Release.

Core-shell nanostructures are powerful platforms for the development of novel nanoscale drug delivery systems with sustained drug release profiles. Coaxial electrospinning is facile and convenient for creating medicated core-shell nanostructures with elaborate designs with which the sustained-release behaviors of drug molecules can be intentionally adjusted. With resveratrol (RES) as a model for a poorly water-soluble drug and cellulose acetate (CA) and PVP as polymeric carriers, a brand-new electrospun core-shell nanostructure was fabricated in this study. The guest RES and the host CA molecules were designed to have a reverse gradient distribution within the core-shell nanostructures. Scanning electron microscope and transmission electron microscope evaluations verified that these nanofibers had linear morphologies, without beads or spindles, and an obvious core-shell double-chamber structure. The X-ray diffraction patterns and Fourier transform infrared spectroscopic results indicated that the involved components were highly compatible and presented in an amorphous molecular distribution state. In vitro dissolution tests verified that the new core-shell structures were able to prevent the initial burst release, extend the continuous-release time period, and reduce the negative tailing-off release effect, thus ensuring a better sustained-release profile than the traditional blended drug-loaded nanofibers. The mechanism underlying the influence of the new core-shell structure with an RES/CA reverse gradient distribution on the behaviors of RES release is proposed. Based on this proof-of-concept demonstration, a series of advanced functional nanomaterials can be similarly developed based on the gradient distributions of functional molecules within electrospun multi-chamber nanostructures.

A comparative investigation of release kinetics of paclitaxel from natural protein and macromolecular nanocarriers in nanoscale drug delivery systems

Understanding the release behaviour of nanodrugs is a crucial step to better assess and control therapeutic outcomes and unfavourable side effects. Herein, we report a systematic study comparing the release kinetics and thermodynamics of paclitaxel (PTX) from supramolecularly assembled sub-micron particles based on natural macromolecules such as zein, whey, casein, bovine serum albumin (BSA) and conventional stabilizers such as pluronic F-127 (poloxamer 407), and β-cyclodextrin (β-CD) to gain insights into the role of carrier chemistry. For this purpose, nanomedicines with statistically indifferent sizes —in the range of 191.0 ± 0.8 nm (BSA) to 243.3 ± 11.6 nm (zein) were prepared (p > 0.05). The zeta potential values ranged from −3.2 ± 1.1 mV (pluronic F-127) to −17.2 ± 1.8 mV (whey) in phosphate buffered saline. The type of nanocarrier significantly influenced the long-term steady-state plateau of the release, resulting in a cumulative release of 70.3 ± 2.0 % of PTX from casein (the highest) and 46.8 ± 4.7 % of PTX from zein (the lowest). Time-resolved release data were analysed with various kinetical models, encompassing zero-order, first-order, Higuchi, Peppas-Sahlin, and Korsmeyer-Peppas kinetics. The analysis revealed that the Korsmeyer-Peppas model best captured the data. For these nanomedicines, the half-life of the encapsulated drugs was found to be 106.4 ± 31.3 h (zein), 4.7 ± 1.2 h (whey), 10.7 ± 1.8 h (pluronic F-127), 6.4 ± 0.9 h (casein), 10.8 ± 3.2 h (β-CD), and 4.0 ± 1.0 h (BSA). TEM characterization revealed differences in the macromolecular arrangement of the active ingredient within these nanocarriers, in addition to the structural differences among the various encapsulating agents. These differences manifested as variations in the internal nanostructures, leading to the creation of distinct microenvironments that could either facilitate or impede the movement of PTX molecules through the encapsulant matrices. In clinical settings, such fine details of nanocarrier design are important: by choosing the most appropriate nanocarrier (or their mixtures), clinicians can fine-tune drug administration to obtain the intended therapeutic window while mitigating the risk of potential negative reactions.

WITHDRAWN: Folic acid Grafted, cell-penetrating peptide conjugated pH-sensitive hydrophobically modified Glycol chitosan nanoparticles for drug delivery in breast cancer

Nanocarriers are an outcome of the fast development of nanotechnology; however, delivering drugs to tumor sites effectively is still a major difficulty. A pH-responsive drug carrier with good cell penetration and targeting ability was developed to release the drug exactly to the cancer site and overcome these limitations.The drug carrier FA-TAT-HGCNPs/PTX, which is pH-responsive, uses folic acid (FA) and TAT peptide to deliver paclitaxel (PTX) for target folate-receptor-overexpressing breast cancer cells. 2-(diisopropylamino) ethyl methacrylate was connected to glycol chitosan (GC) to form HGCNPs. Then TAT and HGCNPs were conjugated and FA was grafted onto the HGCNPs’ hydroxyl group. Physicochemical characterizations of FA-TAT-HGCNPs was also evaluated. The maximum DLE and EE values of the FA-TAT-HGCNPs at pH 8.0 were 74.0 ± 2.22 % and 93.7 ± 2.8 %, respectively. FA-TAT-HGCNPs, for instance, showed stability during long-term storage and lyophilization while exhibiting pH-responsive dissociation properties. The synthesized drug carrier was characterized by FTIR, XRD, SEM, HRTEM, DLS, and Zeta analysis. MTT assay exhibited the high anticancer activity of the FA-TAT-HGCNPs/PTX against the MCF-7 cells, whereas drug-free ones are highly biocompatible. The pharmacokinetic results showed twice the bioavailability of FA-TAT-HGCNPs/PTX compared to HGCNPs/PTX. Unlike FA-HGCNPs/PTX, CLSM analysis showed that FA-TAT-HGCNPs/PTX had a significantly more efficient intracellular uptake in MCF-7 cells. These data have shown the transmembrane ability of TATpeptide,the targeting effects of folate decoration, and the synergistic interaction between them.According to these findings, PTX-loaded FA-TAT-HGCNPs offer a potentially effective nanoscale drug delivery system for the treatment of breast cancer.

Single-Photon Deep-Red Light-Triggered Direct Release of an Anticancer Drug: An Investigative Tumor Regression Study on a Breast Cancer Spheroidal Tumor Model.

Breast adenocarcinoma ranks high among the foremost lethal cancers affecting women globally, with its triple-negative subtype posing the greatest challenge due to its aggressiveness and resistance to treatment. To enhance survivorship and patients' quality of life, exploring advanced therapeutic approaches beyond conventional chemotherapies is imperative. To address this, innovative nanoscale drug delivery systems have been developed, offering precise, localized, and stimuli-triggered release of anticancer agents. Here, we present perylenemonoimide nanoparticle-based vehicles engineered for deep-red light activation, enabling direct chlorambucil release. Synthesized via the reprecipitation technique, these nanoparticles were thoroughly characterized. Light-induced drug release was monitored via spectroscopic and reverse-phase HPLC. The efficacy of the said drug delivery system was evaluated in both two-dimensional and three-dimensional spheroidal cancer models, demonstrating significant tumor regression attributed to apoptotic cell death induced by efficient drug release within cells and spheroids. This approach holds promise for advancing targeted breast cancer therapy, enhancing treatment efficacy and minimizing adverse effects.

The involvement and application potential of exosomes in breast cancer immunotherapy.

Breast cancer has a high incidence and a heightened propensity for metastasis. The absence of precise targets for effective intervention makes it imperative to devise enhanced treatment strategies. Exosomes, characterized by a lipid bilayer and ranging in size from 30 to 150 nm, can be actively released by various cells, including those in tumors. Exosomes derived from distinct subsets of immune cells have been shown to modulate the immune microenvironment within tumors and influence breast cancer progression. In addition, tumor-derived exosomes have been shown to contribute to breast cancer development and progression and may become a new target for breast cancer immunotherapy. Tumor immunotherapy has become an option for managing tumors, and exosomes have become therapeutic vectors that can be used for various pathological conditions. Edited exosomes can be used as nanoscale drug delivery systems for breast cancer therapy, contributing to the remodeling of immunosuppressive tumor microenvironments and influencing the efficacy of immunotherapy. This review discusses the regulatory role of exosomes from different cells in breast cancer and the latest applications of exosomes as nanoscale drug delivery systems and immunotherapeutic agents in breast cancer, showing the development prospects of exosomes in the clinical treatment of breast cancer.

Leprosy: Comprehensive insights into pathology, immunology, and cutting-edge treatment strategies, integrating nanoparticles and ethnomedicinal plants.

Mycobacterium leprae is the causative agent responsible for the chronic disease known as leprosy. This condition is characterized by dermal involvement, often leading to peripheral nerve damage, sensory-motor loss, and related abnormalities. Both innate and acquired immunological responses play a role in the disease, and even in individuals with lepromatous leprosy, there can be a transient increase in T cell immunity during lepromatous reactions. Diagnosing of early-stage leprosy poses significant challenges. In this context, nanoparticles have emerged as a promising avenue for addressing various crucial issues related to leprosy. These include combatting drug resistance, mitigating adverse effects of conventional medications, and enhancing targeted drug delivery. This review serves as a comprehensive compilation, encompassing aspects of pathology, immunology, and adverse effects of multidrug delivery systems in the context of leprosy treatment. Furthermore, the review underscores the significance of ethnomedicinal plants, bioactive secondary metabolites, and nanotherapeutics in the management of leprosy. It emphasizes the potential to bridge the gap between existing literature and ongoing research efforts, with a profound scope for validating traditional claims, developing herbal medicines, and formulating nanoscale drug delivery systems that are safe, effective, and widely accepted.

Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs.

This manuscript offers a comprehensive overview of nanotechnology's impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.

Monitoring the Degradation of Metal‐Organic Framework Drug Nanocarriers by In‐Situ NMR Spectroscopy

AbstractAn accurate characterization methodology is indispensable to design nanoparticle‐based drug delivery system (DDS) adapted to specific diseases and therapies. However, characterization techniques employed to investigate drug release and nanoparticle degradation require separating the nanoparticles from their suspension media, which can lead to artefacts. Therefore, there is a clear need to implement novel versatile in‐situ methods. Here, we report the use of in‐situ NMR spectroscopy to monitor drug delivery processes from MOF nanocarriers, both in solution and in the solid state simultaneously. In‐situ 1H NMR investigation of nanoMIL‐100(Al) suspension in phosphate medium enabled recording the trimesate ligand loss in the solid phase and the ligand release in the liquid phase as a function of time. Simultaneously, 27Al NMR enabled assessing the progressive replacement of carboxylate ligands by phosphates leading to the formation of new aluminum species. Using the same strategy, we also compared the degradation of nanoMIL‐100(Al) loaded with two drug analogs, highlighting an effect of metal‐ligand complexing strength. Furthermore, our in‐situ technique is applicable to studying the reaction of paramagnetic nanoMIL‐100(Fe) in the liquid phase. This work offers an alternative to ex‐situ techniques for understanding the degradation mechanism of MOF nanocarriers and could be an asset for other nanoscale DDSs.

Microfluidic development of brain-derived neurotrophic factor loaded solid lipid nanoparticles: An in vitro evaluation in the post-traumatic brain injury neuroinflammation model

Microfluidic-based nanoscale drug delivery systems have risen to prominence in the field of precision nanomedicine in recent years. This intriguing innovation could provide unique therapeutic prospects in the treatment of serious disorders as traumatic brain injury, a potentially fatal condition that is widespread during childhood. According to current scientific study, neurotrophins are vital for the healing of injured brain parenchyma, and the brain-derived neurotrophic factor (BDNF) in particular may have significant regenerative effects. To address BDNF-related pharmacokinetic constraints, microfluidic-assisted manufacturing of BDNF-loaded solid lipid nanoparticles (BDNF-SLNs) was carried out, and following evaluation, the formulation demonstrated optimum characteristics in terms of size (190.3 ± 10.1 nm), PDI (0.180 ± 0.023), and ζ-potential (– 39.2 ± 1.30 mV). Short-term stability studies and the haemolysis assay verified the formulation's biocompatibility, while an in vitro permeability analysis revealed an increase in the Papp of the encapsulated BDNF (1.27x10−5 cm/s) as compared to plain BDNF (9.31x10−6 cm/s). The in vitro mimicked neuroinflammatory model demonstrated an enhanced decrease in nitrite production and Nos mRNA levels using BDNF-SLNs compared to plain BDNF as a control, validating the proficiency of the microfluidic-based drug delivery systems as pioneering and valuable approaches for the brain delivery of biologicals.

Rational design of a nonclassical liposomal nanoscale drug delivery system for innovative cancer therapy

AbstractAdvanced drug delivery systems are widely considered to be powerful approaches for treating cancer and many other diseases because of their superior ability to improve pharmacokinetics, promote lesion‐targeted delivery efficacy, and/or reduce the toxic effects of diverse therapeutics. Owing to the unique biomimetic structure of lipid bilayers surrounding aqueous cavities, liposomes have been found to encapsulate various therapeutics, ranging from small molecules with different hydrophobicities to biomacromolecules. With the advent of surface PEGylation, stealth liposomes with excellent in vivo long‐circulating behaviors have been generated, thus these liposomes have been extensively explored for the development of liposomal drugs with greatly improved in vivo pharmacokinetic behaviors by functioning as delivery vehicles. Inspired by their successes in clinical practice, stealth liposomes have recently been utilized as the main building scaffold or surface coating layers of other nanoparticulate formulations, which are coined as nonclassical liposomal nanoscale drug delivery systems (NDDSs) in this review, to enable the rational design of next‐generation liposomal nanomedicine. Therefore, after overviewing the latest progress in the development of conventional liposome‐based nanomedicine, we will introduce the development of these nonclassical liposomal NDDSs as well as their innovative cancer treatment strategies. We will subsequently provide a critical perspective on the future development of new cancer nanomedicines based on these rationally designed nonclassical liposomal NDDSs.

Photo-responsive doxorubicin delivery: Nanogel systems based on azobenzene and host-guest interactions enhanced by squeezing action

Conventional chemotherapy methods impact both normal and cancerous cells; therefore, it is essential to design drug delivery systems to reduce undesired drug effects. Nano-scaled drug delivery systems have the advantage of high retention time in blood as well as the capability of conventional penetration into tissue barriers. In this study, light-sensitive biocompatible nanogels with a core-shell structure have been synthesized and characterized as drug delivery system loaded with doxorubicin (DOX). These smart nanogels possess a hydrophobic core, coated with hydrophilic starch polymeric chains, which are modified with β-cyclodextrin (βCD). The core-shell formation is based on host-guest interaction between azobenzene rings as photochromic agents and βCD hydrophobic cavities. The mechanism of drug release is based on the cis-trans isomerization of azobenzene molecules upon light irradiation and dissociation of crore-shell entities. Due to this isomerization, shrinkage of hydrophobic core and removal of shell occurred simultaneously, which assist the drug release. In conclusion, a nanoscale carrier was designed with sustainable drug release under light irradiation as an external and non-contact stimulus. The synthesized nanogels were characterized by FT-IR, 1H NMR, SEM, DLS, and TEM. In addition, the MTT assay proposed that the viability of the A-431 cells has plunged in the presence irradiated nanogels, also histological studies were performed to evaluate the efficacy of the prepared nanogels in cancerous tissues.

Nanogels Based on N,N-Dimethylacrylamide and β-Cyclodextrin Triacrylate for Enhanced Solubility and Therapeutic Efficacy of Aripiprazole.

Aripiprazole (ARZ) is a medication used for the treatment of various diseases such as schizophrenia, bipolar disorder, major depressive disorder, autism, and Tourette's syndrome. Despite its therapeutic benefits, ARZ is characterized by a poor water solubility which provoked the development of various delivery systems in order to enhance its solubility. In the present work, a nanoscale drug delivery system based on N,N-dimethylacrylamide (DMAA) and β-cyclodextrin triacrylate (β-CD-Ac3) as potential aripiprazole delivery vehicles was developed. The nanogels were synthesized by free radical polymerization of DMAA in the presence of β-CD-Ac3 as a crosslinking agent and then loaded with ARZ via host-guest inclusion complexation. The blank- and drug-loaded nanogels were evaluated using different methods. Fourier transform infrared (FTIR) spectroscopy was employed to confirm the incorporation of β-CD moieties into the polymer network. Dynamic light scattering (DLS) was used to study the size of the developed systems. The samples exhibited a monomodal particle size distribution and a relatively narrow dispersity index. The hydrodynamic diameter (Dh) of the gels varied between 107 and 129 nm, with a tendency for slightly larger particles as the β-CD-Ac3 fraction increased. Loading the drug into the nanocarrier resulted in slightly larger particles than the blank gels, but their size was still in the nanoscopic range (166 to 169 nm). The release profiles in PBS were studied and a sustained release pattern with no significant burst effect was observed. A cytotoxicity assessment was also conducted to demonstrate the non-toxicity and biocompatibility of the studied polymers.

Morusin-Cu(II)-indocyanine green nanoassembly ignites mitochondrial dysfunction for chemo-photothermal tumor therapy

Nanoscale drug delivery systems derived from natural bioactive materials accelerate the innovation and evolution of cancer treatment modalities. Morusin (Mor) is a prenylated flavonoid compound with high cancer chemoprevention activity, however, the poor water solubility, low active pharmaceutical ingredient (API) loading content, and instability compromise its bioavailability and therapeutic effectiveness. Herein, a full-API carrier-free nanoparticle is developed based on the self-assembly of indocyanine green (ICG), copper ions (Cu2+) and Mor, termed as IMCNs, via coordination-driven and π-π stacking for synergistic tumor therapy. The IMCNs exhibits a desirable loading content of Mor (58.7 %) and pH/glutathione (GSH)-responsive motif. Moreover, the photothermal stability and photo-heat conversion efficiency (42.8 %) of IMCNs are improved after coordination with Cu2+ and help to achieve photothermal therapy. Afterward, the released Cu2+ depletes intracellular overexpressed GSH and mediates Fenton-like reactions, and further synergizes with ICG at high temperatures to expand oxidative damage. Furthermore, the released Mor elicits cytoplasmic vacuolation, expedites mitochondrial dysfunction, and exerts chemo-photothermal therapy after being combined with ICG to suppress the migration of residual live tumor cells. In vivo experiments demonstrate that IMCNs under laser irradiation could excellently inhibit tumor growth (89.6 %) through the multi-modal therapeutic performance of self-enhanced chemotherapy/coordinated-drugs/ photothermal therapy (PTT), presenting a great potential for cancer therapy.

Observation of antitumor mechanism of GE11-modified paclitaxel and curcumin liposomes based on cellular morphology changes

Curcumin and paclitaxel are widely used as anti-tumor hydrophobic model drugs for the designation of smart tumor-targeting nanocarriers and the study of the correlation between structural characteristics of nanoparticles and in vivo therapeutic efficacy. Various signaling pathways on cell growth and proliferation have been comprehensively studied in vitro and in vivo under the action of curcumin and paclitaxel nanoparticles. In this paper, we prepared EGFR-targeted GE11 peptide-modified curcumin and paclitaxel compound liposomes (CUR-PTX@GE11-L). The tumor suppression mechanism of CUR-PTX@GE11-L is observed from the aspects of drug release behavior, changes of cell morphology, liver retention, and tumor-targeting efficiency. We hope it can provide a new vision for the rational construction of smart nanoscale drug delivery system through the observation of cytotoxic effects of CUR-PTX@GE11-L, especially on the cellular morphology change.Graphical

Core-Shell Nanoparticles for Pulmonary Drug Delivery.

Nanoscale drug delivery systems have provoked interest for application in various therapies on account of their ability to elevate the intracellular concentration of drugs inside target cells, which leads to an increase in efficacy, a decrease in dose, and dose-associated adverse effects. There are several types of nanoparticles available; however, core-shell nanoparticles outperform bare nanoparticles in terms of their reduced cytotoxicity, high dispersibility and biocompatibility, and improved conjugation with drugs and biomolecules because of better surface characteristics. These nanoparticulate drug delivery systems are used for targeting a number of organs, such as the colon, brain, lung, etc. Pulmonary administration of medicines is a more appealing method as it is a noninvasive route for systemic and locally acting drugs as the pulmonary region has a wide surface area, delicate blood-alveolar barrier, and significant vascularization. A core-shell nano-particulate drug delivery system is more effective in the treatment of various pulmonary disorders. Thus, this review has discussed the potential of several types of core-shell nanoparticles in treating various diseases and synthesis methods of core-shell nanoparticles. The methods for synthesis of core-shell nanoparticles include solid phase reaction, liquid phase reaction, gas phase reaction, mechanical mixing, microwave- assisted synthesis, sono-synthesis, and non-thermal plasma technology. The basic types of core-shell nanoparticles are metallic, magnetic, polymeric, silica, upconversion, and carbon nanomaterial- based core-shell nanoparticles. With this special platform, it is possible to integrate the benefits of both core and shell materials, such as strong serum stability, effective drug loading, adjustable particle size, and immunocompatibility.