Physicochemical properties and micro-interaction between micro-nanoparticles and anterior corneal multilayer biological interface film for improving drug delivery efficacy: the transformation of tear film turnover mode.

Recently, various novel drug delivery systems have been developed to overcome ocular barriers in order to improve drug efficacy. We have previously reported that montmorillonite (MT) microspheres (MPs) and solid lipid nanoparticles (SLNs) loaded with the anti-glaucoma drug betaxolol hydrochloride (BHC) exhibited sustained drug release and thus intraocular pressure (IOP) lowering effects. Here, we investigated the effect of physicochemical particle parameters on the micro-interactions with tear film mucins and corneal epithelial cells. Results showed that the MT-BHC SLNs and MT-BHC MPs eye drops significantly prolonged the precorneal retention time due to their higher viscosity and lower surface tension and contact angle compared with the BHC solution, with MT-BHC MPs exhibiting the longest retention due to their stronger hydrophobic surface. The cumulative release of MT-BHC SLNs and MT-BHC MPs was up to 87.78% and 80.43% after 12 h, respectively. Tear elimination pharmacokinetics study further confirmed that the prolonged precorneal retention time of the formulations was due to the micro-interaction between the positively charged formulations and the negatively charged tear film mucins. Moreover, the area under the IOP reduction curve (AUC) of MT-BHC SLNs and MT-BHC MPs was 1.4 and 2.5 times that of the BHC solution. Accordingly, the MT-BHC MPs also exhibit the most consistent and long-lasting IOP-lowering effect. Ocular irritation experiments showed no significant toxicity of either. Taken together, MT MPs may have the potential for more effective glaucoma treatment.

An inorganic-organic-polymeric nanovehicle for targeting delivery of doxorubicin: Rational assembly, pH-stimulus release, and dual hyperthermia/chemotherapy of hepatocellular carcinoma.

Efficiently synergistic therapy of hepatocellular carcinoma (HCC) by chemotherapeutic drug and photothermal agent remains a considerable challenge. Here, we report a nanodrug that integrates specific hepatoma-targeted delivery, pH-triggered drug release, and cooperative photothermal-chemotherapy function. By grafting the easily self-assembled CuS@polydopamine (CuS@PDA) nanocapsulation with polyacrylic acid (PAA), an inorganic-organic-polymeric hybrid nanovehicle was developed as a dual photothermal agent and carrier for loading antitumor drug-doxorubicin (DOX) through electrostatic adsorption and chemical linking antibody against GPC3 commonly overexpressed in HCC, resulting in the nanodrug, CuS@PDA/PAA/DOX/GPC3. The multifunctional nanovehicle had excellent biocompatibility, stability, and high photothermal conversion efficiency, due to the rationally designed binary CuS@PDA photothermal agent. The 72-h accumulative drug release in pH 5.5 tumor microenvironment can reach up to 84%, far higher than 15% measured in pH 7.4 condition. Notably, in contrast to the merely 20% survival rate of H9c2 and HL-7702 cells exposed to free DOX, their viabilities in the nanodrug circumstance can maintain 54% and 66%, respectively, suggesting the abated toxicity to the normal cell lines. When exposed to the hepatoma-targeting nanodrug, the viability of HepG2 cells was found to be 36%, which further drastically declined to 10% plus 808-nm NIR irradiation. Moreover, the nanodrug is potent to cause tumor ablation in HCC-modeled mice, and the therapeutic efficacy can be greatly enhanced under NIR stimulus. Histology analyses reveal that the nanodrug can effectively alleviate the chemical damage to heart and liver, as compared to free DOX. This work thus offers a facile strategy for design of targeting anti-HCC nanodrug toward combined photothermal-chemotherapy.

Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies.

Self-assembly is a simple yet reliable method for constructing nanoscale drug delivery systems. Photoactivatable prodrugs enable controllable drug release from nanocarriers at target sites modulated by light irradiation. In this protocol, a facile method for fabricating photoactivatable prodrug-dye nanoparticles via molecular self-assembly is presented. The procedures for prodrug synthesis, nanoparticle fabrication, physical characterization of the nanoassembly, photocleavage demonstration, and in vitro cytotoxicity verification are described in detail. A photocleavable boron-dipyrromethene-chlorambucil (BC) prodrug was first synthesized. BC and a near-infrared dye, IR-783, at an optimized ratio, could self-assemble into nanoparticles (IR783/BC NPs). The synthesized nanoparticles had an average size of 87.22 nm and a surface charge of -29.8 mV. The nanoparticles disassembled upon light irradiation, which could be observed by transmission electronic microscopy. The photocleavage of BC was completed within 10 min, with a 22% recovery efficiency for chlorambucil. The nanoparticles displayed enhanced cytotoxicity under light irradiation at 530 nm compared with the non-irradiated nanoparticles and irradiated free BC prodrug. This protocol provides a reference for the construction and evaluation of photoresponsive drug delivery systems.

Continuous Manufacturing of Oil in Water (O/W) Emulgel by Extrusion Process.

Pharmaceutical industries and drug regulatory agencies are inclining towards continuous manufacturing due to better control over the processing conditions and in view to improve product quality. In the present work, continuous manufacturing of O/W emulgel by melt extrusion process was explored using lidocaine as an active pharmaceutical ingredient. Emulgel was characterized for pH, water activity, globule size distribution, and in vitro release rate. Additionally, effect of temperature (25°C and 60°C) and screw speed (100, 300, and 600 rpm) on the globule size and in vitro release rate was studied. Results indicated that at a given temperature, emulgel prepared under screw speed of 300 rpm resulted in products with smaller globules and faster drug release.

A pH-Responsive Asymmetric Microfluidic/Chitosan Device for Drug Release in Infective Bone Defect Treatment.

Bacterial infection is currently considered to be one of the major reasons that leads to the failure of guided bone regeneration (GBR) therapy. Under the normal condition, the pH is neutral, while the microenvironment will become acid at the sites of infection. Here, we present an asymmetric microfluidic/chitosan device that can achieve pH-responsive drug release to treat bacterial infection and promote osteoblast proliferation at the same time. On-demand release of minocycline relies on a pH-sensitive hydrogel actuator, which swells significantly when exposed to the acid pH of an infected region. The PDMAEMA hydrogel had pronounced pH-sensitive properties, and a large volume transition occurred at pH 5 and 6. Over 12 h, the device enabled minocycline solution flowrates of 0.51-1.63 µg/h and 0.44-1.13 µg/h at pH 5 and 6, respectively. The asymmetric microfluidic/chitosan device exhibited excellent capabilities for inhibiting Staphylococcus aureus and Streptococcus mutans growth within 24 h. It had no negative effect on proliferation and morphology of L929 fibroblasts and MC3T3-E1 osteoblasts, which indicates good cytocompatibility. Therefore, such a pH-responsive drug release asymmetric microfluidic/chitosan device could be a promising therapeutic approach in the treatment of infective bone defects.

A multi-bioresponsive self-assembled nano drug delivery system based on hyaluronic acid and geraniol against liver cancer.

Herein, a multi-bioresponsive self-assembled nano-drug delivery system (HSSG) was constructed by conjugating the anticancer drug Geraniol (GER) to hyaluronic acid (HA) via a disulfide bond. The HSSG NPs displayed a uniform spherical shape with an average diameter of ∼110 nm, maintained high stability, and realized controlled drug release in the tumor microenvironment (pH/glutathione/hyaluronidase). Results of fluorescence microscopy and flow cytometry verified that HSSG NPs were selectively uptaken by human hepatocellular carcinoma cell lines HepG2 and Huh7 via CD44 receptor-mediated internalization. Studies on H22 tumor-bearing mice demonstrate that HSSG NPs could effectively accumulate at the tumor site for a long period. In vitro and in vivo studies show that HSSG NPs significantly promoted the death of cancer cells while reducing the toxicity as compared to GER. Therefore, the HSSG NPs have great potential in the treatment of tumors.

Stimuli-sensitive nano-drug delivery with programmable size changes to enhance accumulation of therapeutic agents in tumors.

Nano-based drug delivery systems hold significant promise for cancer therapies. Presently, the poor accumulation of drug-carrying nanoparticles in tumors has limited their success. In this study, based on a combination of the paradigms of intravascular and extravascular drug release, an efficient nanosized drug delivery system with programmable size changes is introduced. Drug-loaded smaller nanoparticles (secondary nanoparticles), which are loaded inside larger nanoparticles (primary nanoparticles), are released within the microvascular network due to temperature field resulting from focused ultrasound. This leads to the scale of the drug delivery system decreasing by 7.5 to 150 times. Subsequently, smaller nanoparticles enter the tissue at high transvascular rates and achieve higher accumulation, leading to higher penetration depths. In response to the acidic pH of tumor microenvironment (according to the distribution of oxygen), they begin to release the drug doxorubicin at very slow rates (i.e., sustained release). To predict the performance and distribution of therapeutic agents, a semi-realistic microvascular network is first generated based on a sprouting angiogenesis model and the transport of therapeutic agents is then investigated based on a developed multi-compartment model. The results show that reducing the size of the primary and secondary nanoparticles can lead to higher cell death rate. In addition, tumor growth can be inhibited for a longer time by enhancing the bioavailability of the drug in the extracellular space. The proposed drug delivery system can be very promising in clinical applications. Furthermore, the proposed mathematical model is applicable to broader applications to predict the performance of drug delivery systems.

Antiviral and Antibacterial Sulfated Polysaccharide-Chitosan Nanocomposite Particles as a Drug Carrier.

Drug delivery system (DDS) refers to the method of delivering drugs to the targeted sites with minimal risk. One popular strategy of DDS is using nanoparticles as a drug carrier, which are made from biocompatible and degradable polymers. Here, nanoparticles composed of Arthrospira-derived sulfated polysaccharide (AP) and chitosan were developed and expected to possess the capabilities of antiviral, antibacterial, and pH-sensitive properties. The composite nanoparticles, abbreviated as APC, were optimized for stability of morphology and size (~160 nm) in the physiological environment (pH = 7.4). Potent antibacterial (over 2 µg/mL) and antiviral (over 6.596 µg/mL) properties were verified in vitro. The pH-sensitive release behavior and release kinetics of drug-loaded APC nanoparticles were examined for various categories of drugs, including hydrophilic, hydrophobic, and protein drugs, under different pH values of the surroundings. Effects of APC nanoparticles were also evaluated in lung cancer cells and neural stem cells. The use of APC nanoparticles as a drug delivery system maintained the bioactivity of the drug to inhibit the proliferation of lung cancer cells (with ~40% reduction) and to relieve the growth inhibitory effect on neural stem cells. These findings indicate that the pH-sensitive and biocompatible composite nanoparticles of sulfated polysaccharide and chitosan well keep the antiviral and antibacterial properties and may serve as a promising multifunctional drug carrier for further biomedical applications.

Oral Bioactive Self-Nanoemulsifying Drug Delivery Systems of Remdesivir and Baricitinib: A Paradigmatic Case of Drug Repositioning for Cancer Management.

Oral anticancer therapy mostly faces the challenges of low aqueous solubility, poor and irregular absorption from the gastrointestinal tract, food-influenced absorption, high first-pass metabolism, non-targeted delivery, and severe systemic and local adverse effects. Interest has been growing in bioactive self-nanoemulsifying drug delivery systems (bio-SNEDDSs) using lipid-based excipients within nanomedicine. This study aimed to develop novel bio-SNEDDS to deliver antiviral remdesivir and baricitinib for the treatment of breast and lung cancers. Pure natural oils used in bio-SNEDDS were analyzed using GC-MS to examine bioactive constituents. The initial evaluation of bio-SNEDDSs were performed based on self-emulsification assessment, particle size analysis, zeta potential, viscosity measurement, and transmission electron microscopy (TEM). The single and combined anticancer effects of remdesivir and baricitinib in different bio-SNEDDS formulations were investigated in MDA-MB-231 (breast cancer) and A549 (lung cancer) cell lines. The results from the GC-MS analysis of bioactive oils BSO and FSO showed pharmacologically active constituents, such as thymoquinone, isoborneol, paeonol and p-cymenene, and squalene, respectively. The representative F5 bio-SNEDDSs showed relatively uniform, nanosized (247 nm) droplet along with acceptable zeta potential values (+29 mV). The viscosity of the F5 bio-SNEDDS was recorded within 0.69 Cp. The TEM suggested uniform spherical droplets upon aqueous dispersions. Drug-free, remdesivir and baricitinib-loaded bio-SNEDDSs (combined) showed superior anticancer effects with IC50 value that ranged from 1.9-4.2 µg/mL (for breast cancer), 2.4-5.8 µg/mL (for lung cancer), and 3.05-5.44 µg/mL (human fibroblasts cell line). In conclusion, the representative F5 bio-SNEDDS could be a promising candidate for improving the anticancer effect of remdesivir and baricitinib along with their existing antiviral performance in combined dosage form.

Enzyme/GSH/pH-responsive hyaluronic acid grafted porous silica nanocarriers bearing Ag2S QDs for fluorescence imaging and combined therapy.

Hyaluronic acid (HA) is a naturally polysaccharide that has been used for drug delivery, but is limited by low drug loading capacity and drug leakage in circulation. To improve drug delivery efficient, HA modified porous silica (pSiO2) nanocarriers were successfully prepared for drug delivery and combining therapy. pSiO2 nanocarriers have stable porous structure and high loading capacity, and pSiO2/HA nanocarriers would possess advantages of HA-based carriers and pSiO2 nanoparticles. Herein, pSiO2 nanocarriers were prepared by two-phase process, followed by embedding Ag2S QDs in the pore walls of pSiO2 carriers, which render the carriers photothermal effect. pSiO2 nanocarriers have size of 30 nm, large channels, and high loading capacity (29.3 %). To graft HA, a sensitive linker with alkyl amine and disulfide bond was conjugated on the surface of Ag2S/pSiO2 nanocarriers by three-step reaction. After loading doxorubicin (DOX), HA was grafted via sensitive linker onto the surface of Ag2S/pSiO2 carriers via the formation of amide bonds to seal the loaded drugs. The interaction between HA and CD44 confers the carrier targeting ability to cancer cells. HA coating can be degraded by hyaluronidase resulting in the release of internal cargo. The Ag2S/pSiO2/HA nanocarriers performs responsive drug release and combining photothermal chemotherapy.

Anomalous kinetic study of atenolol release from ATN@DNA a core-shell like structure.

The need for more efficient drug delivery strategies with ultraprecision and control over the release of drugs has led to the growth of more sophisticated drug-releasing systems as a promising alternative to conventional clinical therapies. This new seed of strategies has explored an encouraging property to overcome the inherent problems of traditional therapies. One of the major challenges for any drug delivery system is the introduction of a complete view of the delivery system. In this article, we intend to elucidate the theoretical proof of concept of the electrosynthesis ATN@DNA core-shell like structure as a model system. Therefore, we present a fractal kinetic model (non-exponential model) taking into consideration the concept of time-dependent diffusion coefficient, which was developed using a numerical method with the help of COMSOL Multiphysics. In addition to that, we present here a general fractional kinetic model in sense of the tempered fractional operator, which leads to better characterized memory properties of the release process. Also, the fractional model is compared with the fractal kinetic model and both offer a good description of drug release processes that present anomalous kinetics. The solutions of the fractal and fractional kinetic models are also fitted successfully with our real-release results.

Recent Advancements in Topical Anti-Psoriatic Nanostructured Lipid Carrier-Based Drug Delivery.

Psoriasis is linked with unusual differentiation and hyperproliferation of epidermal keratinocytes that significantly impair the quality of life (QoL) of patients. The present treatment options only provide symptomatic relief and are surrounded by various adverse effects. Recently, nanostructured lipid carriers (NLCs) have emerged as next-generation nanocarriers with better physicochemical characteristics. The current manuscript provides background information on psoriasis, its pathophysiology, existing treatment options, and its limitations. It highlights the advantages, rationale, and mechanism of the permeation of NLCs for the treatment of psoriasis. It further gives a detailed account of various NLC nanoformulations for the treatment of psoriasis. In addition, tabular information is provided on the most relevant patents on NLCs for treating psoriasis. Lastly, light is shed on regulatory considerations related to NLC-like nanoformulations. In the treatment of psoriasis, NLCs display a sustained release drug profile, an ability to incorporate both hydrophobic and hydrophilic drugs, an enhancement in skin hydration, penetrability, retention, and bioavailability of the drug, along with reduced staining potential as compared to conventional ointments, and decreased side effects of drug molecules. This affirms the bright future of NLC nanoformulations in the treatment of psoriasis. However, academic industry collaboration and more sound regulatory controls are required to commercialize the NLC nanoformulations for psoriasis treatment.

The Development and Optimization of Lipid-Based Self-Nanoemulsifying Drug Delivery Systems for the Intravenous Delivery of Propofol.

PURPOSE: Propofol is a relatively short-acting potent anesthetic lipophilic drug used during short surgical procedures. Despite the success of propofol intravenous emulsions, drawbacks to such formulations include inherent emulsion instability, the lack of a safe vehicle to prevent sepsis, and concern regarding hyperlipidemia-related side effects. The aim of the current investigation was to develop a novel, lipid-based self-nanoemulsifying drug delivery system (SNEDDS) for propofol with improved stability and anesthetic activity for human use. METHODS: A series of SNEDDS formulations were developed using naturally obtained medium-chain/long-chain mono-, di-, and triglycerides, glyceryl monocaprylate, and water-soluble cosolvents with hydrogenated castor oil constructing ternary phase diagrams for propofol. The developed SNEDDS formulations were characterized using visual observation, particle size analysis, zeta potential, transmission electron microscopy, equilibrium solubility, in vitro dynamic dispersion and stability, and in vivo sleeping disorder studies in rats. The in vivo bioavailability of the SNEDDSs in rats was also studied to compare the representative formulations with the marketed product Diprivan®. RESULTS: Medium-chain triglycerides (M810) with mono-diglycerides (CMCM) as an oil blend and hydrogenated castor oil (KHS15) as a surfactant were selected as key ingredients in ternary phase diagram studies. The nanoemulsifying regions were identified from the studies and a number of SNEDDSs were formulated. Results from the characterization studies demonstrated the formation of efficient nanosized particles (28-45 nm globule size, 0.10-0.20 PDI) in the optimized SNEDDS with a drug loading of 50 mg/g, which is almost 500-fold higher than free propofol. TEM analysis showed the formation of spherical and homogeneous nanoparticles of less than 50 nm. The dissolution rate of the representative SNEDDS was faster than raw propofol and able to maintain 99% propofol in aqueous solution for around 24 h. The optimized liquid SNEDDS formulation was found to be thermodynamically stable. The intravenous administration of the SNEDDS in male Wistar rats induced a sleeping time of 73-88 min. The mean plasma concentrations after the IV administration of propofol nano-formulations PF2-SNEDDS and PF8-SNEDDS were 1348.07 ± 27.31 and 1138.66 ± 44.97 µg/mL, as compared to 891.44 ± 26.05 µg/mL (p = 0.05) observed after the IV administration of raw propofol. CONCLUSION: Propofol-loaded SNEDDS formulations could be a potential pharmaceutical product with improved stability, bioavailability, and anesthetic activity.

Intestine-inspired wrinkled MXene microneedle dressings for smart wound management.

Composite MXene-based materials are prone to crack propagation, thus limiting their tensile properties. Numerous efforts have been devoted to removing material constraints and fabricating unitary MXene elastic films. Here, for the first time, inspired by the intestinal wrinkles and villi structure, we presented a ductile, biologically friendly, and highly conductive MXene-based microneedle (MMN) dressing composed of stacked MXene film and superfine microneedle arrays through a simple stretching and laser engraving strategy for wound healing. By utilizing photothermal responsive MXene, periodic porous structures, and a temperature-responsive polymer to construct the MMN dressing, the system can act as an effective route for facilitating controllable drug delivery controlled by near-infrared (NIR) irradiation. In addition, superior conductivity imparts them with the capacity to realize continuous and steady monitoring of motion sensing. The practical performance further demonstrated that the versatile MMN dressing showed obvious therapeutic efficacy in vivo animal wound models. Thus, it is believed that MMN dressings with biomimetic structures, controllable drug release, and conductive pathways will open a new chapter for wound management and widen other practical applications in biomedical fields, such as artificial tendons and soft robotics. STATEMENT OF SIGNIFICANCE: MXene-based materials have been demonstrated as critical tools in advancing our understanding of wound healing. However, the rapid crack propagation is a constraint on their tensile properties. Here, inspired by the intestinal wrinkles and villi structure, a single-step method has also been discussed to present a MXene-based microneedle dressing composed of unitary MXene elastic film and superfine microneedle arrays. At the same time, the dressing with biomimetic structures, controllable drug release, and conductive pathways has prospects in intelligent wound management and varieties of related biomedical fields.

A chitosan/fucoidan nanoparticle-loaded pullulan microneedle patch for differential drug release to promote wound healing.

Wound healing is a largely unmet medical issue in trauma, burn, and diabetes. In this study, a pullulan-based and nanoparticle-loaded smart microneedle patch is designed to release drugs differentially based on the needs of wound healing. Chitosan and fucoidan are first used to prepare moxifloxacin (MOX)-loaded nanoparticles (MOXNPs) with a diameter of 258.0 ± 10.86 nm, PDI 0.19 ± 0.06, and surface charge 45.1 ± 3.9 mV. MOXNPs, lidocaine (LH), and thrombin (TH) are then incorporated to a 30 % (w/w) pullulan-based microneedle patch (TH + LH + MOXNPs@MN). TH + LH + MOXNPs@MN possesses uniform and cone-shaped microneedles with a length of 725 µm, demonstrating good biocompatibility, sufficient strength for skin penetration, fast skin dissolution within 55 ± 5 min, rapid release of TH and LH within 1 h, and sustained release of MOX for 24 h. TH + LH + MOXNPs@MN heals mice skin wounds completely within 7 days and restores collagen deposition with accelerated cell proliferation, granulation, and reduced pro-inflammatory cytokines. In conclusion, this study utilizes combined polysaccharides to develop a smart multifunctional microneedle platform that achieves rapid hemostasis/analgesia and sustained bactericidal action. The smart and combined therapy is a potential strategy for high-quality wound healing.

Nanosponges- Versatile Platform as Drug Carrier.

BACKGROUND: Recently, nano-drug delivery systems have become an integral part of the most novel drug delivery systems and have gained considerable importance owing to various advantages such as carriers for poorly soluble drugs, targeting molecules at the desired site, protection from degradation etc. Objective: One of the most studied areas of nanotechnology is nanosponges. The objective of this review was to extensively summarize the various strategies for the preparation, characterization and applications of nanosponges. METHODS: In the current mini-review, we conducted a systemic search of the literature and patent inventions focusing on nanosponges. The summary of the search was inclusive of various aspects of nanosponges, such as drug characteristics to be considered while incorporating in nanosponges, other crucial additives during formulation of nanosponges, methods of preparation, characterization and applications of nanosponges in pharmaceuticals. RESULTS: Nanosponges are nanocarriers for both lipophilic and hydrophilic drugs. These are prepared by different methods such as emulsion-solvent evaporation, solvent method, melting method, ultrasound assisted method etc., and all these methods were less time consuming, more economical and evaluated by sophisticated techniques available for routine analysis. These are among the most feasible alternative to address several formulation difficulties associated with the physicochemical properties of the drug. The porous nature and small particle size are vital properties of the nanosponges that contribute crucially to correcting the drawbacks of the drug. The properties of the nanosponges can be enhanced when combined with cyclodextrins. Extensive research work has been carried out in past to explore cyclodextrin based nanosponges. Besides, it is also used for smart targeting of tumors and for drug release in a sustainable pattern. Nanosponges can be prepared by simple methods. These can be tuned to release the drug by different routes so as to achieve the maximum benefits of the drug. CONCLUSION: Huge amount of research has been carried out on nanosponges as drug carrier. The method of preparation and characterization of nanosponges are quite economical and routinely available. Owing to potential benefits and probable applications, these can be used as efficient carriers for certain drugs. The authors expect that the current review will guide the investigation of the nanosponges as nanodrug delivery systems.

Ultrasound-Triggered Piezocatalysis for Selectively Controlled NO Gas and Chemodrug Release to Enhance Drug Penetration in Pancreatic Cancer.

Nitric oxide (NO) is drawing widespread attention in treating pancreatic ductal adenocarcinoma (PDAC) as a safe and therapeutically efficient technique through modulating the dense fibrotic stroma in the tumor microenvironment to enhance drug penetration. Considerable NO nanogenerators and NO releasing molecules have been developed to shield the systemic toxicity caused by free diffusion of NO gas. However, on-demand controlled release of NO and chemotherapy drugs at tumor sites remains a problem limited by the complex and dynamic tumor microenvironment. Herein, we present an ultrasound-responsive nanoprodrug of CPT-t-R-PEG2000@BaTiO3 (CRB) which encapsulates piezoelectric nanomaterials barium titanate nanoparticle (BaTiO3) with amphiphilic prodrug molecules that consisted of thioketal bond (t) linked chemotherapy drug camptothecin (CPT) and NO-donor l-arginine (R). Based on ultrasound-triggered piezocatalysis, BaTiO3 can continuously generate ROS in the hypoxic tumor environment, which induces a cascade of reaction processes to break the thioketal bond to release CPT and oxidize R to release NO, simultaneously delivering CPT and NO to the tumor site. It is revealed that CRB shows a uniform size distribution, prolonged blood circulation time, and excellent tumor targeting ability. Moreover, controlled release of CPT and NO were observed both in vitro and in vivo under the stimulation of ultrasound, which is beneficial to the depletion of dense stroma and subsequently enhanced delivery and efficacy of CPT. Taken together, CRB significantly increased the antitumor efficacy against highly malignant Panc02 tumors in mice through inhibiting chemoresistance, representing a feasible approach for targeted therapies against Panc02 and other PDAC.

Peptide functionalized actively targeted MoS2 nanospheres for fluorescence imaging-guided controllable pH-responsive drug delivery and collaborative chemo/photodynamic therapy.

The combination of imaging and different therapeutic strategies into one single nanoplatform often demonstrates improved efficacy over monotherapy in cancer treatments. Herein, a multifunctional nanoplatform (labelled as MPRD) based on molybdenum disulfide quantum dots (MoS2 QDs) is developed to achieve enhanced antitumor efficiency by integrating fluorescence imaging, tumor-targeting and synergistic chemo/photodynamic therapy (PDT) into one system. First, polyethylene glycol (PEG)ylated MoS2 QDs (MP) with desirable stability are synthesized via a hydrothermal process using MoS2 QDs and carboxyamino-terminated oligomeric PEG as raw materials. Then, MP were conjugated with arginine-glycine-aspartic acid (RGD) peptide via amidation to form a novel nanocarrier (MPR), which possesses strong blue fluorescence, good biocompatibility and ανß3 receptor-mediated targeting ability. More importantly, MPR generated reactive oxygen species under 808 nm laser activation to realize targeted antitumor PDT. Further doxorubicin (DOX) was loaded onto MPR, which endows MPRD with localized chemotherapy and pH-responsive drug release. The MPRD exhibits improved chemotherapy performance on HepG2 cells (overexpressing integrin ανß3) owing to enhanced cellular uptake mediated by ανß3 receptor and effective drug release triggered by intracellular pH. Notably, MPRD with efficient tumor targeting ability and high chemo/PDT efficacy under NIR laser irradiation is capable of inhibiting HepG2 tumor cell growth both in vitro and in vivo, which is significantly superior to each individual therapy. These findings demonstrate that MPRD holds great potential in effective cancer therapy.

Diffusion-mediated carving of interior topologies of all-natural protein nanoparticles to tailor sustained drug release for effective breast cancer therapy.

Proteins are promising base materials for developing drug carriers with efficient blood circulation due to low possibilities of clearance by macrophages. However, such natural biopolymers have highly sophisticated molecular structures, preventing them from being assembled into nano-platforms with manipulable payload release profiles. Here, we report the self-assembly of two natural proteins (milk casein and rice protein) into protein nanoparticles (NPs, ∼150 nm) with tailorable release profiles. Diffusion of plant-derived paclitaxel (PTX)-containing eugenol into the hydrophobic cores of the NPs and subsequent dialysis to remove eugenol from the cores lead to the carving of the NP interiors. With the increase in the mass ratios of casein and rice protein, this process generates all-natural NPs with PTX loaded in their full cavities, semi-full cavities, or solid cores. These NPs can be efficiently uptaken by breast cancer cells and could kill the cancer cells efficiently. PTX in these NPs demonstrates increasingly sustained in vivo release profiles from full cavities, semi-full cavities, to solid cores, gradually extending its pharmacokinetic profiles in blood plasma to favor drug accumulation in breast tumor models. Consequently, the NPs with solid cores completely inhibit tumor growth in vivo, more effectively than those with full and semi-full cavities. Our work opens up a new avenue to the use of diffusion-mediated nanoscale carving in producing biomaterials with controllable interior topologies relevant to drug release profiles.

Capsaicin-loaded alginate nanoparticles embedded polycaprolactone-chitosan nanofibers as a controlled drug delivery nanoplatform for anticancer activity.

Nanocarrier-based drug delivery systems have been designed into various structures that can effectively prevent cancer progression and improve the therapeutic cancer index. However, most of these delivery systems are designed to be simple nanostructures with several limitations, including low stability and burst drug release features. A nano-in-nano delivery technique is explored to address the aforementioned concerns. Accordingly, this study investigated the release behavior of a novel nanoparticles-in-nanofibers delivery system composed of capsaicin-loaded alginate nanoparticles embedded in polycaprolactone-chitosan nanofiber mats. First, alginate nanoparticles were prepared with different concentrations of cationic gemini surfactant and using nanoemulsion templates. The optimized formulation of alginate nanoparticles was utilized for loading capsaicin and exhibited a diameter of 19.42 ± 1.8 nm and encapsulation efficiency of 98.7 % ± 0.6 %. Likewise, blend polycaprolactone-chitosan nanofibers were prepared with different blend ratios of their solutions (i.e., 100:0, 80:20, 60:40) by electrospinning method. After the characterization of electrospun mats, the optimal nanofibers were employed for embedding capsaicin-loaded alginate nanoparticles. Our findings revealed that embedding capsaicin-loaded alginate nanoparticles in polycaprolactone-chitosan nanofibers, prolonged capsaicin release from 120 h to more than 500 h. Furthermore, the results of in vitro analysis demonstrated that the designed nanoplatform could effectively inhibit the proliferation of MCF-7 human breast cells while being nontoxic to human dermal fibroblasts (HDF). Collectively, the prepared nanocomposite drug delivery platform might be promising for the long-term and controlled release of capsaicin for the prevention and treatment of cancer.