The Dawn of a New Era: Targeting the "Undruggables" with Antibody-Based Therapeutics.

The high selectivity and affinity of antibodies toward their antigens have made them a highly valuable tool in disease therapy, diagnosis, and basic research. A plethora of chemical and genetic approaches have been devised to make antibodies accessible to more "undruggable" targets and equipped with new functions of illustrating or regulating biological processes more precisely. In this Review, in addition to introducing how naked antibodies and various antibody conjugates (such as antibody-drug conjugates, antibody-oligonucleotide conjugates, antibody-enzyme conjugates, etc.) work in therapeutic applications, special attention has been paid to how chemistry tools have helped to optimize the therapeutic outcome (i.e., with enhanced efficacy and reduced side effects) or facilitate the multifunctionalization of antibodies, with a focus on emerging fields such as targeted protein degradation, real-time live-cell imaging, catalytic labeling or decaging with spatiotemporal control as well as the engagement of antibodies inside cells. With advances in modern chemistry and biotechnology, well-designed antibodies and their derivatives via size miniaturization or multifunctionalization together with efficient delivery systems have emerged, which have gradually improved our understanding of important biological processes and paved the way to pursue novel targets for potential treatments of various diseases.

A study on the uptake of methylene blue by biodegradable and eco-friendly carboxylated starch grafted polyvinyl pyrrolidone.

This study is based on the removal of methylene blue (MB) from aqueous solution by cost effective and biodegradable adsorbent carboxymethyl starch grafted polyvinyl pyrolidone (Car-St-g-PVP). The Car-St-g-PVP was synthesized by grafting vinyl pyrolidone onto carboxymethyl starch by free radical polymerization reaction. The structure and different properties of Car-St-g-PVP were determined by 1H NMR, FT-IR, XRD, TGA and SEM. A series of batch experiments were conducted for the removal of MB, The adsorption affecting factors such as temperature, contact time, initial concentration of MB dye, dose of Car-St-g-PVP and pH were studied in detail. The other parameters like the thermodynamic study, kinetics and isothermal models were fitted to the experimental data. The results showed that pseudo 2nd order kinetics and Langmuir's adsorption isotherms were best fitted to experimental data with regression coefficient R2 viz. 0.99 and 0.97. The kinetic study showed that the adsorption mechanism favored chemisorption. The Gibbs free energy (ΔG°) for the adsorption process was found to be -7.31 kJ/mol, -8.23 kJ/mol, -9.00 kJ/mol and -10.10 kJ/mol at 25 °C, 35 °C, 45 °C and 55 °C respectively. The negative values of ΔG° suggested the spontaneous nature of the adsorption process. Similarly, the positive values of entropy (ΔS°) and enthalpy (ΔH°) 91.27 J/k.mol and 19.90 kJ/mol showed the increasing randomness and endothermic nature of the adsorption process. The value of separation factor (RL) was found to be less than one (RL < 1), which supported the feasibility of the adsorption process. The maximum MB removal percentage (% R) was found to be 98.6%. So, these findings show that Car-St-g-PVP can be meritoriously used for the treatment of MB from wastewater.

Investigation of in vivo anti-inflammatory and anti-angiogenic attributes of coumarin-rich ethanolic extract of Melilotus indicus.

Inflammation and angiogenesis are two major contributors to tumourigenesis. Melilotus indicus is traditionally used as an anti-inflammatory agent. The current study was designed to investigate the anti-inflammatory and anti-angiogenic properties of ethanolic extract of M. indicus (Miet) whole plant and its marker compound (coumarin) using a series of in vivo methods. Extraction by maceration was adopted to prepare ethanolic extract. Phytochemical compounds present in Miet were investigated using both qualitative and quantitative methods. In vivo safety profile of Miet was investigated in behavioural studies. Four acute oedema models such as carrageenan, serotonin, histamine-induced paw oedema and xylene-induced ear oedema, and chronic formaldehyde-induced paw oedema model were employed to explore the anti-inflammatory potential of Miet. Chorioallantoic chick membrane assay (CAM) was performed to explore anti-angiogenic potential of Miet. Histopathological evaluations were conducted to access improvement in skin texture of paws. TNF-α ELISA kit was used to study effects of treatment on serum levels of TNF-α. Extraction by maceration resulted in formation of greenish coloured semisolid extract with a high coumarin content. In vivo toxicological studies revealed LD50 of Miet was greater than 8000 mg/kg. Data of acute inflammatory models depicted significant (p < 0.05) inhibition of oedema in Miet, coumarin and standard (piroxicam/indomethacin) treated groups. 750 mg/kg of Miet induced comparable (p > 0.05) anti-inflammatory effects to that of standard-treated groups. Coumarin showed better anti-inflammatory effects in carrageenan-induced paw oedema model as compared with histamine- and serotonin-induced oedema models. Data of chronic inflammatory models also depicted dose-dependent anti-inflammatory attributes of Miet which were comparable with standard treated groups. Significant (p > 0.05) downregulation of TNF-α in serum samples of animals treated with Miet and piroxicam was observed as compared with control group. Furthermore, Miet significantly halted blood vessels formation in CAM assay. Overall, data of the current study highlight that M. indicus has anti-inflammatory and anti-angiogenic potentials, and, thus, can potentially be used as an adjuvant therapy in solid tumours management.

Peptide nucleic acid and amino acid modified peptide nucleic acid analysis by capillary zone electrophoresis.

A rapid, high resolution, and low sample consumption CZE method is developed for peptide nucleic acid (PNA) analysis for the first time. 30% v/v acetonitrile in PNA sample and 20% v/v acetonitrile in 50 mM borax-boric acid (pH 8.7) as BGE were employed after optimization. The calibration curves were linear for PNA concentration ranging from 1 to 50 µmol/L. LOD and LOQ of PNA were 0.2 and 1.0 µmol/L, respectively. Since the commercially available reagent gives rise to huge PNA peak and an apparent impurity peak, the purity of PNA was evaluated to be about 81.4% by CZE method, obviously lower than the supplier's purity value of 99.9% evaluated by RP-HPLC, and also lower than 94.8% determined with RP-HPLC by our research group. The CZE method takes only 5 min, needs only 90 nL PNA, much less than 20 min and 20 µL PNA in RP-HPLC method. Moreover, the CZE method is applicable for the analysis of glutamic acid modified and lysine modified PNAs, they show different migration time with their corresponding complementary PNAs. Our results show CZE provides a new choice for PNA and modified PNA analysis, also their purity or quality evaluation.

Matrix metalloprotease-9 polymorphism and its association with Atherosclerosis - A case-control study in Pakistani population.

OBJECTIVE: To determine the association of matrix metalloproteinase-9 gene with the onset of atherosclerosis in Pakistani population of Punjabi origin. METHODS: The case-control study was conducted from September 2015 to December 2016 at the Government College University, Lahore, Pakistan, and comprised atherosclerosis cases from the Punjab Institute of Cardiology, Lahore, as well as healthy controls. Single nucleotide polymorphismsrs3918242 (Sph1), rs17577 (Sty1) and rs2274756 (Taq1) were selected from the matrix metalloproteinase-9 gene for allelic and genotypic analysis. Direct sequencing and polymerase chain reaction-restriction fragment length polymorphism were performed for genotypic analysis. RESULTS: the 201 subjects, 100(49.8%) were controls and 101(50.2%) were cases. There were 75(75%) males among the controls and 70(69.3%) among the cases. Overall mean age of the controls was 47.3}13.1 years, and that of the cases was 59.2}10.2 years. Positive family history was a significant factor risk for atherosclerosis (p<0.05). Allele T and genotype CT and TT of rs3918242 were more frequent in the cases (p<0.05). Change in nucleotide at Sph1 site led towards -1562C >T polymorphism. The frequency of 'A' allele and 'GA' genotype for rs17577 was significantly higher in the cases (Sty1) (p<0.05). No association was detected between rs2274756 (Taq1) and atherosclerosis (p> 0.05). The co-expression of rs17577 and rs2274756 was significantly related with the onset of atherosclerosis (p<0.05). Haplotypes CAG, TAG and TGG were significantly involved in causing atherosclerosis (p<0.05) whereas CGG was protective against atherosclerosis in this population (p<0.05). CONCLUSIONS: Matrix metalloproteinase-9 gene was identified as a susceptible gene for the onset of atherosclerosis in Pakistani population of Punjabi origin.

Advancements in gene therapy approaches for atrial fibrillation: Targeted delivery, mechanistic insights and future prospects.

Atrial fibrillation (AF) remains a complex and challenging arrhythmia to treat, necessitating innovative therapeutic strategies. This review explores the evolving landscape of gene therapy for AF, focusing on targeted delivery methods, mechanistic insights, and future prospects. Direct myocardial injection, reversible electroporation, and gene painting techniques are discussed as effective means of delivering therapeutic genes, emphasizing their potential to modulate both structural and electrical aspects of the AF substrate. The importance of identifying precise targets for gene therapy, particularly in the context of AF-associated genetic, structural, and electrical abnormalities, is highlighted. Current studies employing animal models, such as mice and large animals, provide valuable insights into the efficacy and limitations of gene therapy approaches. The significance of imaging methods for detecting atrial fibrosis and guiding targeted gene delivery is underscored. Activation mapping techniques offer a nuanced understanding of AF-specific mechanisms, enabling tailored gene therapy interventions. Future prospects include the integration of advanced imaging, activation mapping, and percutaneous catheter-based techniques to refine transendocardial gene delivery, with potential applications in both ventricular and atrial contexts. As gene therapy for AF progresses, bridging the translational gap between preclinical models and clinical applications is imperative for the successful implementation of these promising approaches.

pH-triggered cancer-targeting polymers: From extracellular accumulation to intracellular release.

Stimuli-responsive polymers are promising to achieve targeted delivery, improved stability during circulation, and controlled release of therapeutic and diagnostic agents. Among them, pH-responsive polymeric nanocarriers have attracted significant attention as pH varies in different body fluids (e.g., stomach, intestine, and colon) and intracellular organelles (e.g., endosome, lysosome, and mitochondria) to maintain homeostasis, while distinctive pH changes are also found in certain pathological states. For example, the extracellular environment of the tumor is acidic, which can be employed to drive selective delivery. During the internalization process, since most nanocarriers enter cells upon endocytosis where a drop of pH from 6.5 to 5.0 can occur from endosome to lysosome, pH-sensitive groups have been developed for enhanced cargo release. In this review, both non-covalent and covalent interactions responsive to pH changes are introduced, with a focus on the structure-property relationship and their applications in cancer targeting and endosomal escape.

miR-4482 and miR-3912 aim for 3'UTR of ERG mRNA in prostate cancer.

Ets-related gene (ERG) is overexpressed as a fusion protein in prostate cancer. During metastasis, the pathological role of ERG is associated with cell proliferation, invasion, and angiogenesis. Here, we hypothesized that miRNAs regulate ERG expression through its 3'UTR. Several bioinformatics tools were used to identify miRNAs and their binding sites on 3'UTR of ERG. The selected miRNAs expression was analyzed in prostate cancer samples by qPCR. The miRNAs overexpression was induced in prostate cancer cells (VCaP) to analyze ERG expression. Reporter gene assay was performed to evaluate the ERG activity in response to selected miRNAs. The expression of ERG downstream target genes was also investigated through qPCR after miRNAs overexpression. To observe the effects of selected miRNAs on cell proliferation and migration, scratch assay was performed to calculate the cell migration rate. miR-4482 and miR-3912 were selected from bioinformatics databases. miR-4482 and -3912 expression were decreased in prostate cancer samples, as compared to controls (p<0.05 and p<0.001), respectively. Overexpression of miR-4482 and miR-3912 significantly reduced ERG mRNA (p<0.001 and p<0.01), respectively) and protein (p<0.01) in prostate cancer cells. The transcriptional activity of ERG was significantly reduced (p<0.01) in response to miR-4482 and-3912. ERG angiogenic targets and cell migration rate was also reduced significantly (p<0.001) after miR-4482 and -3912 over-expression. This study indicates that miR-4482 and -3912 can suppress the ERG expression and its target genes, thereby, halt prostate cancer progression. These miRNAs may be employed as a potential therapeutic target for the miRNA-based therapy against prostate cancer.

Removal of As(V) and Cr(VI) with Low-Cost Novel Virgin and Iron-Impregnated Banana Peduncle-Activated Carbons.

This work reports the investigation of activated carbons from virgin banana peduncle (ZR1) and iron-impregnated banana peduncle (ZR2) as adsorbents for the removal of As(V) and Cr(VI) ions from aqueous solutions. Both adsorbents were characterized through the point of zero charge, powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, Brunauer-Emmett-Teller, and Fourier transform infrared spectroscopic techniques. The effects of initial pH, contact time, temperature, and initial concentration on metal ion adsorption were investigated. Adsorbents existed as both crystalline and amorphous species having homogeneous surface cavities and surface area of 749.73 and 369.66 m2/g for ZR1 and ZR2, respectively. The maximum As(V) removal of 79.32 and 69.08% was obtained using ZR1 and ZR2, respectively, whereas the maximum Cr(VI) removal was calculated as 69.73% for ZR1 and 73.78% for ZR2. Kinetic modeling data were found to be best fitted for the pseudo-second-order reaction, and rate constants were calculated. The theoretical adsorption capacities (q m) of ZR1 and ZR2 were calculated through Langmuir and Freundlich models. The maximum As(V) adsorption capacities calculated for ZR1 and ZR2 were 13.33 and 9.066 mg/g, respectively, whereas the maximum Cr(VI) adsorption capacity for both was 13.26 mg/g at 298-328 K. The reaction was endothermic with decreased randomness at the solid-liquid interface due to positive entropy and enthalpy values. All kinetic and thermodynamic parameters showed the feasibility of the adsorption process, and characterization after adsorption indicated ZR1 and ZR2 novel activated carbons as efficient and cheapest biosorbents for removing As(V) and Cr(VI).

Synthesis of bioinspired sorbent and their exploitation for methylene blue remediation.

In this research article, novel starch phosphate grafted polyvinyl imidazole (StP-g-PIMDZs) was synthesized. Firstly, a phosphate group was attached to starch polymer via a phosphorylation reaction. Next, 1-vinyl imidazole (VIMDZ) was grafted on the backbone of starch phosphate (StP) through a free radical polymerization reaction. The synthesis of these modified starches was confirmed by 1H NMR, 31P NMR and FT-IR techniques. The grafting of vinyl imidazole onto StP diminished the crystallinity. Due to the insertion of the aromatic imidazole ring, the StP-g-PIMDZs demonstrated greater thermal stability. The StP and StP-g-PIMDZs were used as sorbents for the adsorption of methylene blue dye (MBD) from the model solution. The maximum removal percentage for starch, StP, StP-g-PIMDZ 1, StP-g-PIMDZ 2 and StP-g-PIMDZ 3 was found to be 60.6%, 66.7%, 74.2%, 85.3 and 95.4%, respectively. The Pseudo second order kinetic model and Langmuir adsorption isotherm were best suited to the experimental data with R2 = 0.999 and 0.99, respectively. Additionally, the thermodynamic parameters showed that the adsorption process was feasible, spontaneous, endothermic and favored chemi-sorption mechanism.

Paraganglioma of urinary bladder: an unusual presentation. pitfalls in diagnosis and treatment.

Paragangliomas of urinary bladder are extremely rare which usually present with characteristic clinical picture in about half of the cases. We report a case where the presentation was unusual, leading to initial misdiagnosis corrected on histological review.

Reliability of MRI in measuring tongue tumour thickness: a 1.5T study.

BACKGROUND: Tongue tumour thickness has been shown to have a correlation with neck nodal metastasis and hence patient survival. Current AJCC guidelines recommend inclusion of tongue tumour thickness measurement in routine radiologic staging. Several studies have attempted to define the accuracy of MRI in measuring tongue tumour thickness. The aim of our study was to compare tongue tumour thickness measured at T2-weighted and STIR sequences with histologic tongue tumour thickness. METHODS: Twenty-eight consecutive patients of tongue cancer who had undergone glossectomy were selected retrospectively. Tumours were measured in both STIR axial and T2-weighted coronal images and compared with histologic tumour thickness on resected specimens. Pearson's analysis was performed to determine the degree of correlation. Paired samples t-test was also used for comparison of mean tumour thicknesses measured on MRI with mean histologic tumour thickness. RESULTS: Pearson correlation analysis showed good correlation of tumour thickness measured on MRI with actual histologic tumour thickness (R=0.876). CONCLUSION: MRI provides a satisfactory prediction of tongue tumour thickness which in turn can be used todetermine the need for elective neck dissection in these patients.

Factors affecting women entrepreneurs' success: a study of small- and medium-sized enterprises in emerging market of Pakistan.

In the present era, women are recognized as successful entrepreneurs through their strong desire, qualities, and capabilities for robust economic development. Due to such an important contribution of women in economic development, we propose to investigate the factors which affect women entrepreneur's success in Pakistan. Data were collected through structured questionnaires from 181 registered SMEs operating in Pakistan. A conceptual model is developed, while SPSS and AMOS software's are used for analysis. The results indicate that the internal factors including the need for achievements, risk-taking, and self-confidence and external factors including economic factors and socio-cultural factors have a positive and significant influence on the success of women-owned enterprises. This research recommends Small and Medium Enterprises Development Authority (SMEDA), policymakers, and practitioners to encourage women entrepreneurs to run their businesses for the long term by providing a variety of incentives and supports related to those internal and external factors. Numerous studies have been conducted to test the different factors' effects on women's entrepreneurial success, but our study investigated some psychological, cultural, and religious factors that are still almost untouched especially in Pakistan. The current study also contributes to the existing literature through empirical shreds of evidence.

In vitro and in vivo evaluation of gellan gum hydrogel films: Assessing the co impact of therapeutic oils and ofloxacin on wound healing.

Herein, we report co-encapsulation of ofloxacin with tea tree or lavender oil in gellan gum based hydrogel films by solvent casting ionotropic gelation method as wound dressing. Prepared films were transparent, flexible, and displayed antioxidant activity with superior antibacterial response against common inhabitants of wound i.e. gram positive and negative bacteria. Solid-state characterization of optimized formulation (OL3 and OT3) revealed successful incorporation of drug and oils in hydrogel structure without any noticeable interaction. In vitro release studies showed an initial burst release but remaining portion released in controlled manner over 48 h from the films and furthermore, presence of oils did not affected the ofloxacin release. Optimized formulation containing ofloxacin and 25% w/w lavender/tea tree oil showed 98% wound contraction in rats after ten days of treatment. Histological images displayed completely healed epidermis. Taken together, our prepared hydrogel films demonstrated favorable features with appreciable antibacterial, wound healing activity and could be useful for the treatment of full thickness wounds.

Glycated albumin based photonic crystal sensors for detection of lipopolysaccharides and discrimination of Gram-negative bacteria.

We present two types of two-dimensional (2D) photonic crystals (PC) hydrogel sensors based on glycated albumin (G-alb) as a proof-of-concept for utilizing recognition between G-alb and bacterial cell surface lipopolysaccharides (LPS) to detect and discriminate Gram-negative bacteria. The G-alb functionalized PC-G-alb hydrogel provides recognition of different LPS via hydrogen bonding and can discriminate different Gram-negative bacteria based on their LPS types. The hydrogel delivered LOD of 0.87 ng mL-1 for E.coli LPS, 153 CFU mL-1 for E.coli, 1.22 ng mL-1 for P.aeruginosa LPS and 225 CFU mL-1 for P.aeruginosa. On the other hand, LPS bioimprinted hydrogel (PC-G-alb-LPSimp) provides selective recognition of E.coli LPS with LOD 0.76 ng mL-1 and for E.coli 58 CFU mL-1, via generation of flexible specific cavities for E.coli and its LPS. The two hydrogels showed remarkable recoveries for both LPS and Gram-negative bacteria in the relevant samples of milk, orange juice, river water, and serum with a short response time of 6-12 min. In the binding process, the hydrogels shrink, and 2D PC particle spacing decreases with diffraction shift from green to blue. The diffraction shifts can be visually observed, measured through Debye's diffraction ring diameter by a laser pointer or determined from a spectrometer.

Elevated Neurokinin-1 Receptor Expression in Uterine Products of Conception Is Associated With First Trimester Miscarriages.

BACKGROUND: Miscarriage is a common complication of early pregnancy, mostly occurring in the first trimester. However, the etiological factors and prognostic and diagnostic biomarkers are not well known. Neurokinin-1 receptor (NK-1R) is a receptor of tachykinin peptide substance P (SP) and has a role in various pathological conditions, cancers, but its association with miscarriages and significance as a clinicopathological parameter are not studied. Accordingly, the present study aimed to clarify the localization and expression for NK-1R in human retained products of conception (POC). The role of NK-1R is not known in miscarriages. MATERIALS AND METHODS: NK-1R expression was assessed in POC and normal placental tissues by immunohistochemistry. Three- to four-micrometer-thin sections of formalin-fixed paraffin-embedded tissues were used for this purpose. Tissues were processed and then immunohistochemically stained with NK-1R antibody. Brain tissue was used as control for antibody. Protein expression was evaluated using the nuclear labeling index (%). Tissues were counterstained with 3,3'-diaminobenzidine (DAB), and microscopy was performed at 10×, 20×, and 40× magnifications. RESULTS: Ten human POC tissues and 10 normal placental tissues were studied by immunohistochemistry to demonstrate the localization of NK-1R. The expression of NK-1R protein was high in all the cases of both groups. NK-1R expression showed no notable differences among different cases of miscarriages as well as normal deliveries at full term regardless of the mother's age and gestational age at which the event occurred. Statistically, no difference was found in both groups, which is in agreement with our hypothesis and previous findings. CONCLUSION: The expression of NK-1R was similar in all the cases, and it was intense. It shows that dysregulation of NK-1R along with its ligand SP might be involved in miscarriages and also involved in normal delivery. Our results provide fundamental data regarding this anti-NK-1R strategy. Thus, the present study recommends that SP/NK-1R system might, therefore, be considered as an emerging and promising diagnostic and therapeutic strategy against miscarriages. Hence, we report for the first time the expression and localization of NK-1R in POC. We suggest NK-1R antagonist in addition to the immunoglobulins and human chorionic gonadotropin to diagnose and treat spontaneous miscarriages.

In-Vitro and In-Vivo Evaluation of Velpatasvir- Loaded Mesoporous Silica Scaffolds. A Prospective Carrier for Drug Bioavailability Enhancement.

The limited aqueous solubility of many active pharmaceutical ingredients (APIs) is responsible for their poor performance and low drug levels in blood and at target sites. Various approaches have been adopted to tackle this issue. Most recently, mesoporous silica nanoparticles (MSN) have gained attention of pharmaceutical scientists for bio-imaging, bio-sensing, gene delivery, drug solubility enhancement, and controlled and targeted drug release. Here, we have successfully incorporated the poorly water soluble antiviral drug velpatasvir (VLP) in MSN. These spherical particles were 186 nm in diameter with polydispersity index of 0.244. Blank MSN have specific surface area and pore diameter of 602.5 ± 0.7 m2/g and 5.9 nm, respectively, which reduced after successful incorporation of drug. Drug was in amorphous form in synthesized VLP-loaded silica particles (VLP-MSN) with no significant interaction with carrier. Pure VLP showed poor dissolution with progressive increment in pH of dissolution media which could limit its availability in systemic circulation after oral administration. After VLP loading in silica carriers, drug released rapidly over a wide range of pH values, i.e., 1.2 to 6.8, thus indicating an improvement in the solubility profile of VLP. These particles were biocompatible, with an LD50 of 448 µg/mL, and in-vivo pharmacokinetic results demonstrated that VLP-MSN significantly enhanced the bioavailability as compared to pure drug. The above results clearly demonstrate satisfactory in-vitro performance, biocompatibility, non-toxicity and in-vivo bioavailability enhancement with VLP-MSN.

Amino-decorated mesoporous silica nanoparticles for controlled sofosbuvir delivery.

The present study describes synthesis of amino-decorated mesoporous silica nanoparticles (MSNs) for sustained delivery and enhanced bioavailability of sofosbuvir. Sofosbuvir is active against hepatitis C virus and pharmaceutically classified as class III drug according to biopharmaceutics classification system (BCS). MSNs were synthesized using modified sol-gel method and the surface was decorated with amino functionalization. Drug loaded MSNs were also grafted with polyvinyl alcohol in order to compare it with the amino-decorated MSNs for sustained drug release. The prepared MSNs were extensively characterized and the optimized formulation was toxicologically and pharmacokinetically evaluated. The functionalized MSNs of 196 nm size entrapped 29.13% sofosbuvir in the pores, which was also confirmed by the decrease in surface area, pore volume and pore size. The drug-loaded amino-decorated MSNs revealed an improved thermal stability as confirmed by thermal analysis. Amino-decorated MSNs exhibited Fickian diffusion controlled sofosbuvir release as compared with non-functionalized and PVA grafted MSNs. Amino-decorated MSNs were deemed safe to use in Sprague-Dawley rats after 14-days exposure as confirmed by the toxicological studies. More interestingly, we achieved a 2-fold higher bioavailability of sofosbuvir in Sprague-Dawley rats in comparison with sofosbuvir alone, and the Tmax was delayed 3-times indicating a sustained release of sofosbuvir.

Advances in chemical modifications of starches and their applications.

Starch is a homopolysaccharide made up of glucose units which are linked together via a glycosidic linkage. This biopolymer is well known for its low cost, biodegradability, renewability and easy availability. In spite of all these beauties, starch has some problems with their solubility in water, retrogradation, loss of viscosity due to rupturing of glucosidic bond when subjected to treatment and absence of some groups of primary importance like different functional groups especially carboxylic group, ester group, ether group and amino group. In order to overcome these shortcomings and enhance its applications, starch must be modified. The modification can be done chemically, physically and enzymatically, but noteworthy one is the chemical modification. In this review article, we focused on the recently used ways of chemical modification such as acid hydrolysis, cross-linking, acetylation/esterification, dual modification, oxidation and grafting of starch, and their properties. This review article highlighted the application of modified starch as an adsorbent for the removal of ammonia, phenol, heavy metals, and dyes.

Preparation, properties and challenges of the microneedles-based insulin delivery system.

Microneedle technology relates to pharmacy, polymer chemistry and micromachining. Microneedle can effectively deliver insulin into systemic circulation across the skin. This process does not affect the activity of insulin. Compared to subcutaneous injection, microneedles cause less pain for their special structure. This review thoroughly discusses the preparation technologies of the microneedles-based insulin delivery system including solid, hollow, dissolving, phase transition, glucose-responsive microneedle patches. In the meantime, the properties, challenges and clinical/commercial status of the microneedles-based insulin delivery system are also discussed in this review.