Glucose-Responsive Self-Regulated Injectable Silk Fibroin Hydrogel for Controlled Insulin Delivery

Stimuli-responsive drug delivery systems are gaining importance in personalized medicine to deliver therapeutic doses in response to disease-specific stimulation. Pancreas-mimicking glucose-responsive insulin delivery systems offer improved therapeutic outcomes in the treatment of type 1 and advanced stage of type 2 diabetic conditions. Herein, we present a glucose-responsive smart hydrogel platform based on phenylboronic acid-functionalized natural silk fibroin protein for regulated insulin delivery. The modified protein was synergistically self-assembled and cross-linked through β-sheet and phenylboronate ester formation. The dynamic nature of the bonding confers smooth injectability through the needle. The cross-linked hydrogel structures firmly hold the glucose-sensing element and insulin in its pores and contribute to long-term sensing and drug storage. Under hyperglycemic conditions, the hydrogen peroxide generated from the sensing element induces hydrogel matrix degradation by oxidative cleavage, enabling insulin release. In vivo studies in a type 1 diabetic Wistar rat model revealed that the controlled insulin release from the hydrogel restored diabetic glucose level to physiological conditions for 36 h. This work establishes the functional modification of silk fibroin into a glucose-responsive hydrogel platform for regulated and functional insulin delivery application

Intrinsically Disordered Ku Protein-Derived Cell-Penetrating Peptides

Efficient delivery of bioactive ingredients into cells is a major challenge. Cell-penetrating peptides (CPPs) have emerged as promising vehicles for this purpose. We have developed novel CPPs derived from the flexible and disordered tail extensions of DNA-binding Ku proteins. Ku-P4, the lead CPP identified in this study, is biocompatible and displays high internalization efficacy. Biophysical studies show that the proline residue is crucial for preserving the intrinsically disordered state and biocompatibility. DNA binding studies showed effective DNA condensation to form a positively charged polyplex. The polyplex exhibited effective penetration through the cell membrane and delivered the plasmid DNA inside the cell. These novel CPPs have the potential to enhance the cellular uptake and therapeutic efficacy of peptide-drug or gene conjugates

The time course of stomach ulceration and its prevention by different doses of PK

Stomach ulceration in mice was induced by oral administration of indomethacin (18 mg/kg body weight). Different doses of PK were used for the experiments. The ulcer indices were measured on different days 4 h after the last dose of PK and the values are mean ± S.E.M. (n = 15). < 0.01, < 0.001 compared to 1day ulcerated untreated mice; < 0.01, < 0.001 compared to the group III mice.<p><b>Copyright information:</b></p><p>Taken from "Healing Potential of (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration."</p><p>http://www.biomedcentral.com/1472-6882/8/3</p><p>BMC Complementary and Alternative Medicine 2008;8():3-3.</p><p>Published online 31 Jan 2008</p><p>PMCID:PMC2266895.</p><p></p

The changes in the tissue EGF expression due to acute gastric ulceration of mice and its regulation by PK and Omez on the 3day of ulceration

The EGF immunostaining was carried out using the peroxidase conjugate. Original magnification × 400. – normal mice, – ulcerated untreated mice, – ulcerated PK-treated mice, – ulcerated Omez-treated mice.<p><b>Copyright information:</b></p><p>Taken from "Healing Potential of (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration."</p><p>http://www.biomedcentral.com/1472-6882/8/3</p><p>BMC Complementary and Alternative Medicine 2008;8():3-3.</p><p>Published online 31 Jan 2008</p><p>PMCID:PMC2266895.</p><p></p

Comparative time dependent activity of PK and Omez in regulating the expression of tissue COX-1 isoform in acute gastric ulcerated mice

The COX-1 expression was quantified using Biovis MV500 software. Data are expressed as means ± SEM for fifteen mice. < 0.05, < 0.01 compared to normal mice, < 0.05 compared to the respective ulcerated mice, < 0.05 compared to the Omez-treated mice. N – normal mice, UU – ulcerated untreated mice, PK – ulcerated PK-treated mice, Omez – ulcerated Omez-treated mice.<p><b>Copyright information:</b></p><p>Taken from "Healing Potential of (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration."</p><p>http://www.biomedcentral.com/1472-6882/8/3</p><p>BMC Complementary and Alternative Medicine 2008;8():3-3.</p><p>Published online 31 Jan 2008</p><p>PMCID:PMC2266895.</p><p></p

Comparative time dependent activity of PK and Omez in regulating the expression of tissue COX-2 isoform in acute gastric ulcerated mice

The COX-2 expression was quantified using Biovis MV500 software. Data are expressed as means ± SEM for fifteen mice. < 0.01 compared to normal mice, < 0.05 compared to the respective ulcerated mice, < 0.05 compared to the Omez-treated mice. N – normal mice, UU – ulcerated untreated mice, PK – ulcerated PK-treated mice, Omez – ulcerated Omez-treated mice.<p><b>Copyright information:</b></p><p>Taken from "Healing Potential of (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration."</p><p>http://www.biomedcentral.com/1472-6882/8/3</p><p>BMC Complementary and Alternative Medicine 2008;8():3-3.</p><p>Published online 31 Jan 2008</p><p>PMCID:PMC2266895.</p><p></p

Comparative time dependent activity of PK and Omez in regulating the expression of tissue EGF in acute gastric ulcerated mice

The EGF expression was quantified using Biovis MV500 software. Data are expressed as means ± SEM for fifteen mice. < 0.001 compared to the normal mice; < 0.001 compared to the respective ulcerated mice, < 0.01 compared to the Omez-treated mice. N – normal mice, UU – ulcerated untreated mice, PK – ulcerated PK-treated mice, Omez – ulcerated Omez-treated mice.<p><b>Copyright information:</b></p><p>Taken from "Healing Potential of (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration."</p><p>http://www.biomedcentral.com/1472-6882/8/3</p><p>BMC Complementary and Alternative Medicine 2008;8():3-3.</p><p>Published online 31 Jan 2008</p><p>PMCID:PMC2266895.</p><p></p

Comparative time dependent activity of PK and Omez in regulating the expression of tissue VEGF in acute gastric ulcerated mice

The EGF expression was quantified using Biovis MV500 software. Data are expressed as means ± SEM for fifteen mice. < 0.01 compared to normal mice, < 0.01 compared to the respective ulcerated mice, < 0.01 compared to the Omez-treated mice. N – normal mice, UU – ulcerated untreated mice, PK – ulcerated PK-treated mice, Omez – ulcerated Omez-treated mice.<p><b>Copyright information:</b></p><p>Taken from "Healing Potential of (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration."</p><p>http://www.biomedcentral.com/1472-6882/8/3</p><p>BMC Complementary and Alternative Medicine 2008;8():3-3.</p><p>Published online 31 Jan 2008</p><p>PMCID:PMC2266895.</p><p></p

Synthesis of 1-Deoxy-1-hydroxymethyl- and 1-Deoxy-1-<i>epi</i>-hydroxymethyl Castanospermine as New Potential Immunomodulating Agents

Two new C-1 epimeric hydroxymethyl castanospermine congeners 2a and 2b, synthesized by stereocontrolled intramolecular double reductive amination of d-glucose derived β-keto ester as a key step, showed impressive immuno-potentiating property. The bioactivity was mediated through up-regulation of TH1/TH2 cytokine ratio. The finding suggested that immunmodulatory activity of polyhydroxylated indolizidine alkaloids can be tuned by minor structural/stereochemical alterations

Functionalized Fluorescent Nanostructures Generated from Self-Assembly of a Cationic Tripeptide Direct Cell-Selective Chemotherapeutic Drug Delivery

Nanodrug delivery systems (NDDs) capable of conveying chemotherapeutics directly into malignant cells without harming healthy ones are of significant interest in the field of cancer therapy. However, the development of nanostructures with the requisite biocompatibility, inherent optical properties, cellular penetration ability, encapsulation capability, and target selectivity has remained elusive. In an effort to develop cell-selective NDDs, we have synthesized a cationic tripeptide Boc-Arg-Trp-Phe-OMe (PA1), which self-assembles into well-ordered spheres in 100% aqueous medium. The inherent fluorescence properties of the peptide PA1 were shifted from the ultraviolet to the visible region by the self-assembly. These fluorescent nanostructures are proteolytically stable, photostable, and biocompatible, with characteristic blue fluorescence signals that permit us to monitor their intracellular entry in real time. We also demonstrate that these tripeptide spherical structures (TPSS) have the capacity to entrap the chemotherapeutic drug doxorubicin (Dox), shuttle the encapsulated drug within cancerous cells, and initiate the DNA damage signaling cascade, which culminates in apoptosis. Next, we functionalized the TPSS with an epithelial-cell-specific epithelial cell adhesion molecule aptamer. Aptamer-conjugated PA1 (PA1–Apt) facilitated efficient Dox delivery into the breast cancer epithelial cell line MCF7, resulting in cell death. However, cells of the human cardiomyocyte cell line AC16 were resistant to the cell killing actions of PA1–Apt. Together, these data demonstrate that not only can the self-assembly of cationic tripeptides like PA1 be exploited for efficient drug encapsulation and delivery but their unique chemistry also allows for functional modifications, which can improve the selectivity of these versatile NDDs