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Specific cellular uptake and sufficient drug release in tumor tissues are important for effective cancer therapy. Hyaluronic acid (HA), a skeleton material, could specifically bind to cluster determinant 44 (CD44) receptors highly expressed on the surface of tumor cells to realize active targeting. Cystamine (cys) is sensitive highly reductive environment inside tumor cells and was used as a connecting arm to connect docosahexaenoic acid (DHA) and chlorin e6 (Ce6) to the HA skeleton to obtain redox-sensitive polymer HA-cys-DHA/Ce6 (CHD). Nanoparticles were fabricated and loaded with chemotherapeutic drug docetaxel (DTX) by physical encapsulation. The prepared nanoparticles had significantly increased uptake by MCF-7 cells that overexpressed CD44 receptors, and DTX was effectively released at high reducing condition. Compared with mono-photodynamic therapy (PDT) or mono-chemotherapy, the prepared nanoparticles exhibited superior anti-tumor effect by inhibiting microtubule depolymerization, blocking cell cycle and generating reactive oxygen species (ROS). In vivo anti-tumor experiments proved that DTX/CHD nanoparticles had the best antitumor response versus DTX and CHD nanoparticles under near-infrared (NIR) irradiation. These studies revealed that redox-responsive DTX-loaded CHD nanoparticles held great potential for the treatment of breast cancer.

Compared with ordinary chemotherapeutic drugs, the variable-size nanoparticles (NPs) have better therapeutic effects and fewer side effects.This review mainly summarizes the strategies used to construct smart, size-tunable nanocarriers based on characteristic factors of tumor microenvironment (TME) to dramatically increase the penetration and retention of drugs within tumors.Nanosystems with changeable sizes based on the TME have been extensively studied in the past decade, and their permeability and retention have been greatly improved, making them a very promising treatment for tumors.

At present, malignant tumours have become one of the most serious diseases that endanger human health. According to a survey on causes of death in Chinese population in early 1990s, the malignant tumours were the second leading cause of death. In the treatment of tumours, the ideal situation is that drugs should target and accumulate at tumour sites and destroy tumour cells specifically, without affecting normal cells and stem cells with regenerative capacity. This requires drugs to be specifically transported to the target organs, tissues, cells, and even specific organelles, like mitochondria, nuclei, lysosomes, endoplasmic reticulum (ER), and Golgi apparatus (GA). The nano drug delivery system can not only protect drugs from degradation but also facilitate functional modification and targeted drug delivery to the tumour site. This article mainly reviews the targeting of nano drug delivery systems to tumour cytoplasmic matrix, nucleus, mitochondria, ER, and lysosomes. Organelle-specific drug delivery system will be a major mean of targeting drug delivery with lower toxicity, less dosage and higher drug concentration in tumour cells.

The bitterness of a drug is a major challenge for patient acceptability and compliance, especially for children. Due to the toxicity of medication, a human taste panel test has certain limitations. Atomoxetine hydrochloride (HCl), which is used for the treatment of attention deficit/hyperactivity disorder (ADHD), has an extremely bitter taste. The aim of this work is to quantitatively predict the bitterness of atomoxetine HCl by a biosensor system. Based on the mechanism of detection of the electronic tongue (E-tongue), the bitterness of atomoxetine HCl was evaluated, and it was found that its bitterness was similar to that of quinine HCl. The bitterness threshold of atomoxetine HCl was 8.61 µg/ml based on the Change of membrane Potential caused by Adsorption (CPA) value of the BT0 sensor. In this study, the taste-masking efficiency of 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) was assessed by Euclidean distances on a principle component analysis (PCA) map with the SA402B Taste Sensing System, and the host–guest interactions were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), nuclear magnetic resonance (NMR) spectroscopy and scanning electron microscopy (SEM). Biosensor evaluation and characterization of the inclusion complex indicated that atomoxetine HCl could actively react with 2-hydroxypropyl-β-cyclodextrin., Graphical abstract The quantitative bitterness of atomoxetine hydrochloride was measured by a biosensor system using quinine hydrochloride as a reference. HP-β-CyD/atomoxetine hydrochloride inclusion complex was prepared to mask the bitter taste, and the efficiency of bitterness suppression by HP-β-CyD was evaluated by biosensor system. Following DSC, X-ray, H-NMR and SEM analysis, it was found that atomoxetine hydrochloride actively reacted with HP-β-CyD.Image, graphical abstract

Sclerosing lipogranuloma (SLG) in children is a rare, benign disease of unknown etiology suspected to be due to abnormal fatty tissue reaction. A 13-year-old girl presented with progressively worsening back pain. Cross-sectional imaging identified a retroperitoneal mass compressing the left ureter as well as infrarenal inferior vena cava atresia with extensive venous collaterals and chronic partially occlusive thromboses of the iliac veins. Surgical biopsy was consistent with SLG and it resolved spontaneously. SLG is typically a disease of adulthood but may be seen in children. The association between inferior vena cava atresia with venous thrombosis and development of SLG has not been reported previously.

The selective infiltration of cell membranes and tissue barriers often blocks the entry of most active molecules. This natural defense mechanism prevents the invasion of exogenous substances and limits the therapeutic value of most available molecules. Therefore, it is particularly important to find appropriate ways of membrane translocation and therapeutic agent delivery to its target site. Cell penetrating peptides (CPPs) are a group of short peptides harnessed in this condition, possessing a significant capacity for membrane transduction and could be exploited to transfer various biologically active cargoes into the cells. Since their discovery, CPPs have been employed for delivery of a wide variety of therapeutic molecules to treat various disorders including cranial nerve involvement, ocular inflammation, myocardial ischemia, dermatosis and cancer. The promising results of CPPs-derived therapeutics in various tumor models demonstrated a potential and worthwhile scope of CPPs in chemotherapy. This review describes the detailed description of CPPs and CPPs-assisted molecular delivery against various tissues and organs disorders. An emphasis is focused on summarizing the novel insights and achievements of CPPs in surmounting the natural membrane barriers during the last 5 years.

Most of the potential therapeutic agents capable to modulate the pathophysiology or treat the neurological disorders and brain tumors are useless in the current modern and advanced era of neuroscience due to the impeding action of biological barriers. Among various therapeutic strategies applied for translocation of drug delivery across the blood-brain barrier (BBB), nanoformulations set an excellent platform for brain targeting by overcoming the biological and chemical barriers and protecting drug from efflux to promote the optimum therapeutic drug concentration in brain parenchyma tissues. Nanocarriers are the most widely studied delivery vehicles for BBB translocation with the efficiency of selectively targeting or exploiting inherent biological molecules, receptors, carriers or mechanisms of the brain. Nearly all of the available drug delivery nanocarriers explored in recent years for brain therapeutics and theranostics are based on lipid or polymeric materials. Polymeric nanoparticles (NPs) and lipid based nanocarriers including liposomes, solid lipid NPs (SLNs) and micelles, etc. are under the direct focus of neuroscientists due to the promising attributes and vast applications in neurological disorders. Surface modification of nanovehicles with proper targeting moiety or coating with surfactants promotes the interaction with endothelial cells and passage of nanocarriers to the brain. This review comprehensively depicts challenges to the brain targeted drug delivery, mechanisms of drug transportation across the BBB, and potential contributions of endogenous cells as NPs delivery cells and novel targeting ligands decorated nanoformulations in imaging, treating and controlling neurological disorders.

Sonodynamic therapy (SDT) has been proposed as a new modality for cancer management through low-intensity ultrasound induced activation of sonosensitizers. Here, we designed a novel redox/enzyme/ultrasound responsive chondroitin sulfate-chlorin e6-lipoic acid nanoplatform loading docetaxel, combining SDT and chemotherapy, for antiproliferation and antimetastasis of melanoma. The reversibly crosslinked and self-assembled nanoparticles possessed monodispersive size distribution, stability in physical conditions, while showing increased uptake with rapid drug release in simulated tumor microenvironment (reductive potentials and degradative hyaluronidase-1). With synthesized ultrasound sensitive polymer backbones, SDT induced the generation of cellular reactive oxygen species and mitochondrial damage, exerting the apoptotic effect through the release of cytochrome C, the expression of cleaved caspase-9 followed by the functional cleaved caspase-3. Chemo-sonodynamic therapy not only inhibited tumor growth and metastasis with reduced metastatic protein expression, but also caused immune response via the release of tumor-associated antigens. It was initially demonstrated that SDT could induce the tumor cell death, therefore having potentials to recruit cytotoxic lymphocytes into tumor sites. Notably, the nanoplatforms exhibited good in vivo stability and blood compatibility, indicating the safety and efficiency in drug delivery. Our work thus presents a convenient approach to fabricate intelligent multifunctional nanoparticles and paves a path for effective cancer therapies.

Multidrug resistance (MDR) of cancer is a persistent problem in chemotherapy. Scientists have considered the overexpressed efflux transporters responsible for MDR and chemotherapy failure. MDR extremely limits the therapeutic effect of chemotherapy in cancer treatment. Many strategies have been applied to solve this problem. Multifunctional nanoparticles may be one of the most promising approaches to reverse MDR of tumor. These nanoparticles can keep stability in the blood circulation and selectively accumulated in the tumor microenvironment (TME) either by passive or active targeting. The stimuli-sensitive or organelle-targeting nanoparticles can release the drug at the targeted-site without exposure to normal tissues. In order to better understand reversal of MDR, three main strategies are concluded in this review. First strategy is the synergistic effect of chemotherapeutic drugs and ABC transporter inhibitors. Through directly inhibiting overexpressed ABC transporters, chemotherapeutic drugs can enter into resistant cells without being efflux. Second strategy is based on nanoparticles circumventing over-expressed efflux transporters and directly targeting resistance-related organelles. Third approach is the combination of multiple therapy modes overcoming cancer resistance. At last, numerous researches demonstrated cancer stem-like cells (CSCs) had a deep relation with drug resistance. Here, we discuss two different drug delivery approaches of nanomedicine based on CSC therapy.

Additional file 2. Described the experimental methods.

Additional file 1: Figure S1. The synthesis steps of CS-ADH-Rh-LA conjugates. Figure S2 The characterization of CS-ADH-Rh-LA. The 1H NMR (A) and 13 C NMR (B) spectra of CS, CS-ADH-Rh and CS-ADH-Rh-LA copolymers. (C) The FT-IR spectra of CS, CS-ADH-Rh and CS-ADH-Rh-LA copolymers. Figure S3 The DLS result of C-NPs after incubating in 20 µM DTT solution for 24 h. Figure S4 Size changes of C-NPs and NC-NPs in 10% FBS solution within 6 days. Figure S5 Transcellular transport assay of C6/C-NPs in A549 cells. Scar bar, 100 µm. Figure S6 The cell viability of A549 cells after incubating with different concentrations of DTX. Figure S7 Cytotoxicity result of CS-ADH-LA with different concentrations. Figure S8 The CLSM images of ROS production in A549 cells after incubating with different solutions with/without SDT treatment. Scar bar, 100 µm. Figure S9 The H&E staining results of heart, liver, spleen, lung and kidney after incubating with NS, C-NPs with SDT, Taxotere®, DTX with Rh, DTX/C-NPs and DTX/C-NPs with SDT. Scar bar, 100 µm. Figure S10 TUNEL images of Left tumor tissues from bilateral tumor bearing mice treated with NS, C-NPs + SDT, Taxotere®, DTX + Rh, DTX/C-NPs and DTX/C-NPs + SDT. Scar bar, 100 µm.

BackgroundLung cancer was regarded as the most common type of tumors worldwide, and the relative lethality was considerably high. However, since the tumor tissues located in deeper parts in human bodies, the traditional technologies like photodynamic therapy could not reached desired effect. Sonosensitizers can induce sonodynamic therapy, possessing the benefits of deep penetration and effective tumor inhibition by generating reactive oxygen. Besides, ultrasound possessed the ability of deep penetration, which showed favorable tumor inhibition effect.ResultsA redox/enzyme/ultrasound responsive Rhein-chondroitin sulfate nano-preparation encapsulating docetaxel was initially fabricated. The nanoparticles show increased cellular uptake with quick drug release, revealing good stability and monodispersed form in physiological environment. Also, Rhein could induce apoptosis and mitochondrial membrane potential change, enhancing the expression of apoptosis-related protein. Further, the inhibited metastasis and angiogenesis of cancer cells by sonodynamic therapy would lead to reduced expression of M2 type macrophages.ConclusionRhein was firstly discovered to possess the sonodynamic effect in this work by generating plenty of reactive oxygen after treating by ultrasound. The nanoplatform enhanced synergistic anti-tumor effect by both sonodynamic therapy and chemotherapeutic efficacy, and showed benign biocompatibility, which might pave a way for the investigation of chemo-sonodynamic therapy with different cancers.

Background Lung cancer is the most common type of tumour worldwide. Its relative lethality is considerably high. However, since the tumour tissues are located deep within the human body, traditional technologies, such as photodynamic therapy, do not have the desired effect. Sonosensitisers can penetrate deeply into tissues, and sonodynamic therapy (SDT) effectively inhibits tumours by generating reactive oxygen species. Ultrasound can also penetrate deeply, with a favourable tumour inhibition effect. Results A redox/ultrasound-responsive Rhein-chondroitin sulphate-based nano-preparation encapsulating docetaxel was fabricated. The nanoparticles displayed increased cellular uptake with quick drug release, good stability, and a monodispersed form in the physiological environment. Rhein induced apoptosis and altered mitochondrial membrane potential, which enhanced the expression of apoptosis-related proteins. SDT inhibited the metastasis and angiogenesis of cancer cells and activated anti-tumour capacity by reducing the expression of M2 macrophages. Conclusions The potential of Rhein for SDT was demonstrated. Production of reaction oxygen species was markedly enhanced after ultrasound treatment. The nanoplatform enhanced the synergistic anti-tumour effects of SDT and chemotherapeutic efficacy. The approach was biocompatibility. The findings could inform investigations of chemo-SDT for different cancers.

In this study, galactosamine-modified poly(ethylene glycol)-poly(lactide) (Gal-PEG-PLA) polymers were synthesized and Gal-PEG-PLA/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles named as GPP micelles were designed to promote the oral absorption of a hydrophobic drug, curcumin (CUR). CUR-loaded Gal-PEG-PLA/TPGS micelles (CUR@GPP micelles) were fabricated using the thin-film dispersion method. CUR@GPP micelles had a size of about 100 nm, a near-neutral zeta potential, drug loading (DL) of 14.6%, and sustained release properties. GPP micelles with high Gal density (GPP3 micelles) were superior in facilitating uptake in epithelial cells and improving intestinal permeation. In situ intestinal absorption studies suggested that the jejunum and ileum were the best absorption segments in the intestinal tract. Additionally, biodistribution results revealed that GPP3 micelles could be remarkably taken up by the jejunum and ileum. Pharmacokinetics revealed that the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from 0 to 24 h (AUC0–24) for CUR@GPP3 micelles were both significantly increased, and that the relative bioavailability of CUR@GPP3 micelles to CUR-loaded mPEG-PLA/TPGS micelles (CUR@PP micelles) was 258.8%. Furthermore, CUR-loaded micelles could reduce damage to the liver and intestinal tissues. This study highlights the importance of Gal content in the design of targeting nanocarrier Gal-modified micelles, which have broad prospects for oral delivery of hydrophobic drugs. Therefore, they could serve as a promising candidate for targeted delivery to the liver.

Purpose: To compare recurrence rate of primary pterygium following excision with mitomycin c verses excisionwith amniotic membrane transplant.Study Design: Quasi experimental study.Place and Duration of Study: Qazi Hussain Ahmad Medical Complex, Nowshera, from January 2019 to June2019.Material and Methods: One hundred and two patients presenting for the first time with pterygium were includedin the study and were divided into two groups. Patients having conjunctivitis, blephritis, keratitis or any otherocular inflammatory condition and patients having history of chemical burns and symblepharon were excludedfrom the study. Group A underwent surgical excision with 0.02% mitomycin–C application for 3 minutes andGroup B was surgically treated with application of amniotic membrane. Patients of both groups were followed upfor six months to detect recurrence of pterygium. Data was analyzed using SPSS version 20. Frequency andpercentages were calculated for categorical data like age, gender and recurrence rate. Recurrence rate wasstratified among age and sex to see the effect modifiers.Results: Mean age in both groups was 39.98 ± 9.11 years. In group A, 64.70% patients were males and in groupB, 62.74% patients were male. Recurrence of Pterygium was seen in 21.5% patients in group A and 7.84% ingroup B. The difference was statistically significant with a p value of 0.05.Conclusion: Recurrence rate of primary pterygium following excision with mitomycin C is higher than excisionwith amniotic membrane transplant

Electrospun, an advanced technology, has been successfully employed for fibre production and offers many merits in novel drug delivery systems (DDSs). In recent years, electrospun has gained significant attention and attraction of the scientists in soaring numbers. This technology is superior to other technologies in fabricating the fibres which range from micrometers to manometers scale. The selection of appropriate polymers, electrospun processes and electrospun parameters play important roles in controlling the drug release while, treating serious illness. Besides, electrospraying process has similar characteristics to the electrospun and is presented briefly here. Further, in vivo and in vitro evaluations of the electrospun nanofibers are comprehensively discussed. In addition, the electrospun nanotechnology has been exploited to design drug release systems, investigate drug's pharmacokinetics and further develop DDS. The electrospun nanofibers improve bioactivity of various types of drugs including water-insoluble, soluble, anticancer and antibacterial drugs and genetic materials. In the end, the prospects and challenges in the process of designing drug-loaded electrospun nanofibers are discussed in detail.

Paclitaxel (PTX) belongs to a class of taxane anti-tumor drug used for the clinic treatment of breast cancer, ovarian cancer, non-small-cell lung cancer, and so on. PTX has poor water solubility and oral bioavailability. It is generally administered via intravenous (i.v.) infusion. Traditional PTX injectable preparations contain Cremophor-EL and ethanol to improve its solubility, which would result in adverse reactions like severe hypersensitivity, neutropenia, etc. Adverse reactions can be reduced only by complicated pretreatment with glucocorticoid and antihistamines drugs and followed by PTX slow infusion for three hours, which has brought significant inconvenience to the patients. Though, a new-generation PTX formulation, Abraxane, free of Cremophor-EL and ethanol, is still being administrated by frequent i.v. infusions and extremely expensive. Therefore, non-injection administration of PTX is urgently needed to avoid the side effects as well as reduce inconvenience to the patients. Recently, a variety of non-injection drug delivery systems (DDSs) of PTX have been developed. This review aims to discuss the progress of non-injectable administration systems of PTX, including oral administration systems, vaginal administration systems, implantable DDSs, transdermal DDSs and intranasal administration for the future study and clinical applications.

In this report, redox/enzyme responsive chondroitin sulfate-ss-deoxycholic acid (CSCD) conjugates were synthesized using cystamine as the linkage which could self-assemble to form self-assembled nanoparticles (175.6 + 5.2 nm) in the aqueous environment. Docetaxel (DTX) was loaded in nanoparticles with desired loading efficiency for the inhibition of tumor growth and metastasis of melanoma. Interestingly, nanoparticles were demonstrated to respond to hyaluronidase-1 (Hyal-1) which could degrade chondroitin sulfate (CS) backbones. In this case, we designed dual-sensitive nanoparticles with enhanced drug release pattern under the presence of glutathione (GSH)/Hyal-1. Compared with Taxotere®, CSCD nanoparticles significantly improved the DTX distribution in tumors and lungs with about 4.4-fold higher area-under-the-curve (AUC) value. In situ tumor volume and pulmonary metastatic formation were reduced upon the administration of DTX-loaded CSCD nanoparticles via DTX-induced apoptosis and decreased metastasis-promotion protein expression. With only minor cytotoxicity, CSCD nanoparticles could be promising nano-drug delivery systems for successful management of melanoma.

The blood–brain barrier (BBB) restricts the transport of potential therapeutic moieties to the brain. Direct targeting the brain via olfactory and trigeminal neural pathways by passing the BBB has gained an important consideration for delivery of wide range of therapeutics to brain. Intranasal route of transportation directly delivers the drugs to brain without systemic absorption, thus avoiding the side effects and enhancing the efficacy of neurotherapeutics. Over the last several decades, different drug delivery systems (DDSs) have been studied for targeting the brain by the nasal route. Novel DDSs such as nanoparticles (NPs), liposomes and polymeric micelles have gained potential as useful tools for targeting the brain without toxicity in nasal mucosa and central nervous system (CNS). Complex geometry of the nasal cavity presented a big challenge to effective delivery of drugs beyond the nasal valve. Recently, pharmaceutical firms utilized latest and emerging nasal drug delivery technologies to overcome these barriers. This review aims to describe the latest development of brain targeted DDSs via nasal administration. Chemical compounds studied in this article Carbopol 934p (PubChem CID: 6581) Carboxy methylcellulose (PubChem CID: 24748) Penetratin (PubChem CID: 101111470 ) Poly lactic-co-glycolic acid (PubChem CID: 23111554) Tween 80 (PubChem CID: 5284448 )

In March 2017, Pakistan formally took the decision to begin a process of incorporating the Federally Administered Tribal Territories into the framework of regular Pakistani law. This article offers...

A terahertz broadband linear-to-circular (LTC) polarization deflection is proposed in this paper. By introducing a hybrid resonant structure with birefringent and broadband phase response, the polarizer can convert a linearly polarized (LP) wave to a circularly polarized (CP) wave with a deflection angle of 30°. In the 8.45% 3-dB axis ration (AR) bandwidth, the simulation results indicate that the average polarization conversion efficiency of the units reaches approximately 80% and the reflectance is 0.63 at 0.36 THz. The proposed polarization deflection has great potential application value in radar and wireless communication.

Curcuminoids (CURs), a series of derivatives in turmeric ( Curcuma longa), are commonly discovered to control the deterioration of cancers. However, the physiochemical properties and the original side effects of many CURs complexes put barriers in their medical applications. To address them, the investigation of metal-based complexes with CURs is in progress. The complexes were summarized according to articles in recent years. The results showed that the complexes improved the physicochemical properties or therapeutic performances compared with pure CURs. Further, it is possible for the novel complexes to be applied in chemical detecting, paramagnetic-luminescent and bio-imaging fields. Therefore, the formation of the metal-based CURs complexes (MBCCs) is beneficial for the development of CURs especially in medical fields.

We theoretically and experimentally demonstrate a label-free terahertz biosensor with ultrahigh sensitivity and distinctive discretion. By constructing a metal-air-metal (MAM) metamaterial perfect absorber (MPA) with a metallic paired-ring resonator array, a hollow microfluidic channel, and a backed reflector, a novel dual-band absorptive sensing platform is proposed in the THz range. The near field coupling by dipole-induced trapped modes and the magnetic momentum caused a vertical to transverse power flux that dramatically enhanced the electromagnetic field on top of the metasurface and in the microfluidic channel, respectively. Both the resonant modes exhibit perfect absorption and produce ultrahigh normalized sensitivities of 0.47/RIU (refractive index unit, RIU) and 0.51/RIU at 0.76 THz and 1.28 THz, respectively. Compared with conventional microfluidic sensors, the salient advantages of our design are the perfect spatial overlap for light-matter interaction and polarization insensitivity. Characterized by THz time domain spectroscopic absorption quantification measurements with different concentrations of bovine serum albumin (BSA), the proposed sensor exhibits promising applications in microfluidic biosensing.

Traditional cancer therapies carry a risk of serious side effects and toxicity. Developing an alternative treatment modality that is highly effective, has low toxicity and is noninvasive is urgently required. Here, we exploited molybdenum oxide (MoOx) nanosheets as a drug carrier and degradable photothermal agent to provide a chemo-photothermal combination cancer therapy. The MoOx nanosheets were synthesized by a one-pot hydrothermal method and then modified with pluronic F127 to improve physiological stability and biocompatibility. The F127-modified nanosheets (MoOX@F127) showed ultrahigh drug loading efficiency (DLE) of doxorubicin (DOX) (DLE%; 65%, W(load DOX)/[W(load DOX) + WMoOx@F127]), strong near-infrared (NIR) absorption and desirable pH-dependent degradability. After intravenous injection, MoOx@F127 nanosheets were degraded at physiological pH and were rapidly excreted from normal organs, while they were effectively accumulated and retained long-term in the more acidic tumor tissue. This simultaneously ensured effective tumor ablation after NIR irradiation and avoided long-term retention and toxicity in vivo. Compared to chemotherapy or photothermal therapy alone, in vitro and in vivo tumor ablation studies have shown a notably improved synergistic effect of the combination therapy. Our study presents a multifunctional nanosystem with a desirable degradability for chemo-photothermal combination cancer therapy that has great potential in biomedical applications.

Curcumin (CUR), one of the major extracts of turmeric, has gained extensive attention owing to its extraordinary benefits as anti-cancer, anti-bacterial, anti-ulcerative, anti-depressant, anti-inflammatory and wound healing agent. However, a major barrier in its application lies in its inherent nature of low water solubility, instability, and short half-life. Different strategies have been adopted to overcome these barriers like preparing nano-sized formulations and exploiting stable and hydrophilic derivatives, and collaborative drug delivery. Nanopreparations could maintain the pharmacological effect of drugs, even the holistic effects of drug extracts. In addition, nanopreparations based on novel materials make it a reality to regulate the drug release rate according to the various environmental conditions. The therapeutic applications and novel investigated nanopreparations of CUR for prevention and treatment of various diseases, especially, cancer and inflammatory disorders are discussed in this review. Refereed/Peer-reviewed

Advanced strategies have been developed to overcome limitations of traditional pharmacological treatments like low specificity and severe side effects. Remarkably, the application of nano drug delivery systems (NDDS) to improve intracellular uptake has promising prospects. Among other proposed materials, metal-organic frameworks (MOFs) formed by the assembly of metal ions and organic ligands exhibit excellent advantages as a nanocarrier, such as high drug loading, excellent biocompatibility and biodegradability, controllable drug release as well as easy modification. Thus, MOFs are widely used in NDDS. Based on this, scientists devoted much effort to designing multi-functional and versatile MOFs to achieve desirable therapeutic effects. This review introduced the latest MOFs for tumor treatment. Here, the classification of MOFs was introduced and, some responsive MOFs to control the release behavior of drugs were reviewed. Besides, some advanced active targeting MOFs to improve drug accumulation in tumor were summarized. Finally, the remaining challenges encountered by MOFs were discussed and proposed, which could provide guidance for developing more intelligent NDDS based on the promising materials of MOFs.

The therapeutic efficacy of most chemotherapeutic drugs is hampered by low water solubility, poor stability, serious side effects, and lack of tumor selectivity. To solve these issues, chondroitin sulfate (CS)-based redox-responsive nanoparticles were developed. The amphiphilic polymer, CS-alpha-tocopherol succinate (TOS) (CS-CYS-TOS), was constructed by conjugating TOS on the CS backbone via cystamine (CYS) as a redox-sensitive linker, which could self-assemble to form polymeric nanoparticles in phosphate buffer saline (PBS). The resulting nanoparticles had low critical aggregation concentration (CAC) of 0.027–0.040 mg/mL, small size, and narrow size distribution. The docetaxel (DTX)-loaded nanoparticles were fabricated by the sonication method with high drug loading (DL) of 17.06% ± 0.97. The dynamic light scattering (DLS) and transmission electron microscope (TEM) had shown spherical nanoparticles with a size of 170.7 nm ± 2.8 and ~160 nm, respectively, and zeta potential of −26.5 mV ± 1.5. The results of the reduction-triggered disassembly behavior study and in vitro release study revealed the redox-sensitive potential of CS-CYS-TOS nanoparticles. The nanoparticles exhibited time-dependent qualitative and quantitative uptake by melanoma cells. The Sulforhodamine B (SRB) assay indicated the safety of carrier material and enhanced anti-tumor activity of DTX-loaded nanoparticles. The in vivo biological performance of nanoparticles in tumor-bearing mice was evaluated and DTX/CS-CYS-TOS nanoparticles were superior in terms of tumor volume inhibition than other formulations. This nanoparticulate system responded to the reducing conditions in tumor cells, released drugs quickly and thoroughly, thereby improved the efficacy of chemotherapy.

Poly(β-amino ester)s (PβAE)s are considered as the most potent alternative to viral vectors, which has been increasingly proposed for targeting gene delivery, because of their excellent transfection performance. The self-assembled nanoparticles formed from interaction with nucleic acids showed good biodegradable and hydrophilic nature, which make PβAE superior over other polycationic polymers. PβAEs exhibit different kinetic profiles and tunable charge density, which can be fabricated using a diverse library of building blocks and binding various conjugates to improve transfection efficiency. The rational designing of PβAE is a critical step to achieve various requirements of gene delivery, anticancer and antimicrobial drug delivery, and nanochaperones. This review presents a revised recapitulation of the synthesis protocols, formulation aspects, and biomedical applications of PβAEs. Within each of these titles, a critical analysis of the design principles and strategies along with examples, opportunities, and challenges are discussed.

The standard chemotherapy is facing the challenges of lack of cancer selectivity and development of drug resistance. Currently, with the application of nanotechnology, the rationally designed nanocarriers of chondroitin sulfate (CS) have been fabricated and their unique features of low toxicity, biocompatibility, and active and passive targeting made them drug delivery vehicles of the choice for cancer therapy. The hydrophilic and anionic CS could be incorporated as a building block into- or decorated on the surface of nanoformulations. Micellar nanoparticles (NPs) self-assembled from amphiphilic CS-drug conjugates and CS-polymer conjugates, polyelectrolyte complexes (PECs) and nanogels of CS have been widely implicated in cancer directed therapy. The surface modulation of organic, inorganic, lipid and metallic NPs with CS promotes the receptor-mediated internalization of NPs to the tumor cells. The potential contribution of CS and CS-proteoglycans (CSPGs) in the pathogenesis of various cancer types, and CS nanocarriers in immunotherapy, radiotherapy, sonodynamic therapy (SDT) and photodynamic therapy (PDT) of cancer are summarized in this review paper.

Paclitaxel is an anti-tumor drug that is effective in the treatment of various tumors, but its applications are limited due to its poor water solubility, short biological half-life and severe side effects. A tumor has many features that are different from normal tissues, such as mild acidity, strong reducing environment and over-expressed certain enzymes. Many smart micelles sensitive to internal or external stimuli have been developed that could realize the release of drug at tumor site. In addition, micelles could improve the aqueous solubility, potentiate therapeutic efficacy and, reduce the side effects of drugs to the normal tissues. This review summarizes recent studies on stimuli-responsive micelles for the delivery of paclitaxel and their potential applications in cancer therapy.

A metamaterial perfect absorber (MPA) based terahertz dual-band ultrasensitive sensor is theoretically and experimentally demonstrated here. The transverse resonances induced by the absorptive channel with hybrid Fano meta-atoms beget the higher dual-band normalized sensitivities of 0.53/RIU and 0.59/RIU at 0.92 THz and 0.69 THz, respectively. The experimental result of Bovine Serum Albumin (BSA) sample exhibit promising applications for microfluidic biosensing.

Terahertz dynamic coding metasurface has always aroused extensive attention for many years. However, complicated bias circuit design still is a significant challenge. Here, we design a terahertz metasurface composed of the unit cells with bias circuit integrated. We have experimentally demonstrated the anomalous reflection of the terahertz metasurface in a wide frequency band (0.32 to 0.49 THz) by employing different coding sequences. This work provides potential applications for the development of interesting dynamic terahertz devices.

A reflective polarization converter with HEMT -embedded net-grid metasurface is demonstrated here. The polarizer can convert a linearly polarized (LP) wave to its cross-polarized wave at four resonant frequencies with a high polarization conversion ratio, and it can convert the LP wave to a circularly polarized (CP) wave at the other eight resonant frequencies. The novel polarization converter may greatly benefit potential applications in terahertz ultrafast polarization manipulation.

Paclitaxel (PTX) is one of the natural products used as first- or second-line treatment of cancer. It has a wide spectrum of activity against various cancer types, but low solubility in water, and toxicity to normal tissues such as hypersensitivity reaction and neuropathy limited its applications. The serious endeavors have been made to design and fabricate a more favorable nanoformulation lowering the inherent toxicity and side effects of PTX. The polymer-drug conjugates as a class of polymer-based nanomedicines have been reported to reduce adverse effects, enhance uptake and accumulation in tumor cells, potentiate therapeutic efficacy and improve patient compliance compared to polymer-encapsulated drugs. Collectively, very “old” PTX as cytotoxic drug bound to polymer has enormous potential and broad prospects. In this review, we mainly pay attention to summarize progress in the polymer-PTX conjugates designed and evaluated in recent decades to potentiate the therapeutic efficacy and tackle adverse effects of PTX.

AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and/or nucleic acids. AGEs have been shown to play a role in various conditions including cardiovascular disease and diabetes. In this study, we hypothesized that AGEs play a role in the “multiple hit hypothesis” of nonalcoholic fatty liver disease (NAFLD) and contribute to the pathogenesis of hepatosteatosis. We measured the effects of various mouse chows containing high or low AGE in the presence of high or low fat content on mouse weight and epididymal fat pads. We also measured the effects of these chows on the inflammatory response by measuring cytokine levels and myeloperoxidase activity levels on liver supernatants. We observed significant differences in weight gain and epididymal fat pad weights in the high AGE-high fat (HAGE-HF) versus the other groups. Leptin, TNF-α, IL-6, and myeloperoxidase (MPO) levels were significantly higher in the HAGE-HF group. We conclude that a diet containing high AGEs in the presence of high fat induces weight gain and hepatosteatosis in CD-1 mice. This may represent a model to study the role of AGEs in the pathogenesis of hepatosteatosis and steatohepatitis.

Eosinophils are nonspecific harbingers of esophageal disease. We report on the incidence and features of esophageal eosinophilia diagnosed at our center in 2011 and compare the findings with previously published results between 1980-1988 and 2000-2002. Eosinophils per high-power field were counted in esophageal biopsies from 675 patients who underwent 710 endoscopic procedures between January 1, 2011, and December 31, 2011. Of these, 209 (33%) patients were infiltrated with eosinophils; the other 466 (67%) showed no pathological changes. The highest concentrations of eosinophils were observed in the distal esophagus. Our findings also indicate that esophageal eosinophilia fluctuates over time.

Celiac disease is a gluten enteropathy that is treated with dietary elimination of gluten. Exposure to nondietary sources of gluten, which are used in the manufacture of products such as plastics, dental equipment, and cosmetics, can also trigger or exacerbate disease. We report the case of a 9-year-old child who presented with nonspecific abdominal discomfort with abnormal serology for celiac disease. She underwent duodenal biopsies that revealed Marsh 3B histopathology. Despite strict dietary elimination of gluten, she continued to be symptomatic and demonstrate positive serum markers for active disease. It was then discovered that the child was exposed to gluten from her orthodontic retainer that contained a plasticized methacrylate polymer. Gluten is a common additive in plastics. She discontinued its use and demonstrated symptom resolution and complete normalization of serology. All possible sources of gluten, including nondietary, must be considered when managing a child with celiac disease.

Two hundred thirty-four cases of primary gastrointestinal tract malignancy were diagnosed at the histopathology laboratory of Asir Central Hospital over a four-year period, from 1987 to 1990. The current study is a retrospective analysis of these cases regarding rank orders, distribution according to nationality, age and sex, primary sites affected and the histopathologic pattern. Eighty-eight percent of our cases were Saudi and 12% were non-Saudi nationals. The mean age of patients was 60 +/- 16 years with a male:female ratio of 2:1. Primary liver cancer was the most common malignancy (29%), followed by gastric cancer (27%), colorectal cancer (21%) and esophageal cancer (13%). Comparison of our findings to those from other provinces of the Kingdom are also included.

OBJECTIVES It is not known whether the prevalence of childhood esophagitis has changed over time. In children, the intraepithelial eosinophil is considered the hallmark of esophageal inflammation. This study compares the prevalence of intraepithelial eosinophils in esophageal biopsies obtained from 1980-1988 and 2001-2002. PATIENTS AND METHODS This study reevaluated all of the esophageal biopsies obtained at a single center during 2 periods: 1980-1988 and 2001-2002. Histological appearances were characterized and eosinophils per high-power field were quantified. RESULTS In total, 1058 esophageal biopsies from 510 subjects were reviewed. Between 1980 and 1988, 247 biopsies from 188 subjects were evaluated. Of these, 62 subjects met the criteria for esophageal disease, and 106 had no specific pathological changes. Between 2001 and 2002, 811 biopsies from 322 subjects were evaluated. Of these, 132 subjects met the criteria for esophageal disease, and 182 had no specific pathological changes. A statistically significant increase in the prevalence of esophageal inflammatory disease was observed comparing the recent group with the remote group. Eosinophilic esophagitis is thought to be distinct from other types of esophagitis in pathogenesis, epidemiology, histology, and treatment. Some suggest the prevalence of eosinophilic esophagitis has increased in recent years. We sought evidence for an increase in histological changes consistent with eosinophilic esophagitis. No matter whether histology consistent with eosinophilic esophagitis was defined as 25, 20, 15, or 10 eosinophils per high-power field, no increase in prevalence was found. CONCLUSIONS This study demonstrated no evidence for a change in the density of eosinophilic infiltrates in esophageal biopsies during the 22-year study period. The study showed a statistically significant increase in the prevalence of esophageal inflammatory disease across the same period.

Six hundred ninety-seven histologically confirmed cases of cancer were seen in the three-year period, 1987 to 1989, at Asir Central Hospital in Abha, Saudi Arabia. Percentage (crude relative) frequencies of cancer at various sites were determined. The most common cancer sites among males were skin, liver, lymphoid tissue (i.e., non-Hodgkin's lymphomas), bladder,, blood (leukemias), stomach, colon, esophagus, central nervous system, and prostate. Skin cancer was also the most common cancer among females, followed by breast, lymphoid tissue (non-Hodgkin's lymphomas), blood (leukemias), thyroid, stomach, colon, oral cavity, esophagus, and cervix.

Exogenous lipoid pneumonia induced by modified animal fat (ghee) in 10 children is described. The initial presentation was of an acute or chronic pneumonia which proved refractory to anti-microbial chemotherapy. The radiological presentation varied from mild perihilar consolidation to diffuse and extensive bilateral involvement, particularly of the posterior lung segments. A history of administration of ghee provided the initial clue to the diagnosis, which was confirmed by demonstration of fat by bronchoalveolar lavage or by open lung biopsy. Eight of the 10 patients improved with either steroid therapy alone or steroids with resection of the most involved lung segments. One patient, who had extensive superinfection with Mycobacterium fortuitum, died. Lipoid pneumonia should be considered in the differential diagnosis of 'non-resolving' pneumonias in communities where the cultural practice of infant feeding with ghee is prevalent. Public awareness through health education about the potential hazards of this practice to infants and children can contribute to reduce the incidence of the problem.