Promises of Lipid-based Drug Delivery Systems in the Management of Breast Cancer.

Breast cancer is one of the leading types among the common non-cutaneous malignancies in women. All the curative methods available for its treatment are minimal due to their toxicity issues and dose-related side effects. Various evolving nanotechnology techniques displayed the opportunity to target breast cancer.

Doxorubicin-Loaded Mixed Micelles for the Effective Management of Skin Carcinoma: In Vivo Anti-Tumor Activity and Biodistribution Studies.

Skin cancer is an alarming concern due to increased radiation and chemical exposure. Doxorubicin is a drug prescribed for various cancers by parenteral route. Apart from the pharmaceutical challenge of being a biopharmaceutical classification system (BCS) Class III drug, the side effects of doxorubicin are also a great concern.

Assessing the pharmacokinetics and toxicology of polymeric micelle conjugated therapeutics.

: Analogous to nanocarriers such as nanoparticles, liposomes, nano lipoidal carriers, niosomes, and ethosomes, polymeric micelles have gained significance in the field of drug delivery. They have attracted scientists worldwide by their nanometric size, wide range of polymers available for building block synthesis, stability and potential to enhance the targeting and safety of drugs. Incorporation of drugs within the interior of polymeric micelles alters the drug pharmacokinetics, which generally results in increased efficiency.

Enhancement effects of process optimization technique while elucidating the degradation pathways of drugs present in pharmaceutical industry wastewater using Micrococcus yunnanensis.

Pharmaceutical effluents released from industries are accountable to deteriorate the aquatic and soil environment through indirect toxic effects. Microbes are adequately been used to biodegrade pharmaceutical industry wastewater and present study was envisaged to determine biodegradation of pharmaceutical effluent by Micrococcus yunnanensis. The strain showed 42.

Delivery of Docetaxel to Brain Employing Piperine-Tagged PLGA-Aspartic Acid Polymeric Micelles: Improved Cytotoxic and Pharmacokinetic Profiles.

In this study, poly-(lactic-co-glycolic) acid (PLGA) was conjugated with aspartic acid and was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. Docetaxel-loaded polymeric micelles were prepared, and piperine was tagged. The neuroblastoma cytotoxicity studies revealed a substantially higher cytotoxic potential of the developed system to that of plain docetaxel, which was further corroborated by cellular uptake employing confocal laser scanning microscopy.

Aspartic acid tagged carbon nanotubols as a tool to deliver docetaxel to breast cancer cells: Reduced hemotoxicity with improved cytotoxicity.

The present study aimed to explore the potential of hydroxylated carbon nanotubes (CNTnols) conjugated with aspartic acid for the delivery of docetaxel (DTX) to breast cancer cells. The conjugate was well-characterized by FT-IR, NMR, XRD and FE-SEM. The nanoconjugate offered a hydrodynamic diameter of 86.

Advanced Approaches of Bioactive Peptide Molecules and Protein Drug Delivery Systems.

Despite the fact that protein and peptide therapeutics are widely employed in the treatment of various diseases, their delivery is posing an unembellished challenge to the scientists. It was discovered that delivery of these therapeutic systems through oral route is easy with high patient compliance. However, proteolytic degradation and absorption through the mucosal epithelium are the barriers in this route.

Aspartic acid derivatized hydroxylated fullerenes as drug delivery vehicles for docetaxel: an explorative study.

The objective of the present study was to deliver docetaxel to cancerous cells with enhanced efficacy and safety profile, using aspartic acid linked fullerenols. This aspartic acid derivatized fullerenol conjugate linked with docetaxel was characterized by UV, FT-IR and NMR spectroscopy. Studies for particle size, PDI, zeta potential and FE-SEM were also performed.

Chitosan-palmitic acid based polymeric micelles as promising carrier for circumventing pharmacokinetic and drug delivery concerns of tamoxifen.

Being a BCS class II drug and a good substrate for microsomal enzymes, tamoxifen (TAM) offers a scope for research owing to poor aqueous solubility and compromised bioavailability. The present study designs a novel copolymer derived from palmitic acid and chitosan, and evaluate the derived TAM-loaded micelles for various delivery attributes. The nanometric micellar carriers not only substantially loaded the drug, but also controlled the rate of release of TAM.

Improved cellular uptake, enhanced efficacy and promising pharmacokinetic profile of docetaxel employing glycine-tethered C-fullerenes.

Water dispersible fullerenes were synthesized by tethering with glycine. The glycinated fullerenes were conjugated to docetaxel and characterized using FT-IR and NMR. The nanometric drug-loaded carriers were able to release drug at cancer cell pH, but resisted drug release at plasma pH.

Dermatokinetics as an Important Tool to Assess the Bioavailability of Drugs by Topical Nanocarriers.

Background: Now-a-days, numerous nanocarrier-based drug products for topical applications are present in the market and number of similar products are being researched. To estimate the amount of drug delivery to skin, the scientists have now established techniques for separation of skin layers for the determination of drug concentrations. This forms the basis of pharmacokinetics of drug(s) in skin, i.

PLGA-soya lecithin based micelles for enhanced delivery of methotrexate: Cellular uptake, cytotoxic and pharmacokinetic evidences.

Biocompatible and biodegradable polymers like PLGA have revolutionized the drug delivery approaches. However, poor drug loading and substantially high lipophilicity, pave a path for further tailing of this promising agent. In this regard, PLGA was feathered with biocompatible phospholipid and polymeric micelles were developed for delivery of Methotrexate (MTX) to cancer cells.

Chitosan-modified PLGA polymeric nanocarriers with better delivery potential for tamoxifen.

Breast cancer is believed as the second most common cause of cancer-related deaths in women for which tamoxifen is frequently prescribed. Despite many promises, tamoxifen is associated with various challenges like low hydrophilicity, poor bioavailability and dose-dependent toxicity. Therefore, it was envisioned to develop tamoxifen- loaded chitosan-PLGA micelles for potential safe and better delivery of this promising agent.

Chitosan-Stearic Acid Based Polymeric Micelles for the Effective Delivery of Tamoxifen: Cytotoxic and Pharmacokinetic Evaluation.

Chitosan is a widely employed polysaccharide with positive zeta-potential and better tissue/cell adhesion. Its hydrophilicity, high viscosity, and insolubility at physiological pH are major hurdles in proper utilization of this macromolecule. Therefore, it was conjugated with biocompatible stearic acid and the conjugate was employed to develop polymeric micelles for delivery of tamoxifen to breast cancer cells.

C60-fullerenes for delivery of docetaxel to breast cancer cells: A promising approach for enhanced efficacy and better pharmacokinetic profile.

Docetaxel has always attracted the researchers owing to its promises and challenges. Despite marked efficacy, concerns like poor aqueous solubility, lower bioavailability, poor tissue penetration and dose related side-effects offer further scope of research on docetaxel. The present study aims to explore the potential of C60-fullerenes in the delivery of docetaxel to cancerous cells.

Developmental changes in the glycosylation of glycoprotein hormone free alpha subunit during pregnancy.

Glycoprotein hormone alpha subunit, in its free form (free alpha), is a major placental product. Its glycosylation was found to change dramatically during the advancement of pregnancy. In this study, we have analyzed these glycosylation changes in five normal pregnancies.

Expression, purification, and bioassay of human stanniocalcin from baculovirus-infected insect cells and recombinant CHO cells.

Stanniocalcin is a calcium- and phosphate-regulating glycoprotein hormone that was first described in fish where it functions in preventing hypercalcemia. Human cDNA clones encoding the homolog of stanniocalcin have been recently isolated. In this study, the full-length cDNA coding for human stanniocalcin (hSTC) was cloned into both baculovirus and CHO expression vectors.

Production and purification of novel secreted human proteins.

Our objective during the last year was to produce and purify 50-80 novel, secreted human proteins identified via high throughput cDNA sequencing and computer analysis. We chose the baculovirus expression vector system in order to obtain secreted, correctly folded, bioactive proteins. Recombinant (re-)baculoviruses (BV) were plaque purified, and pulse-labeling was used to verify the synthesis and secretion of the re-proteins.

Differential reactivities of recombinant glycosylated ectodomains of mouse and human thyrotropin receptors with patient autoantibodies.

We expressed the extracellular domain of the mouse TSH receptor (mET-gp) using the baculovirus expression system. The recombinant protein was identified as mET-gp by immunoblotting and N-terminal amino acid sequencing. Carbohydrate analysis of the recombinant protein showed that the protein is glycosylated.

Requirement of glycosylation of the human thyrotropin receptor ectodomain for its reactivity with autoantibodies in patients' sera.

To understand the role of glycosylation on autoantibody reactivity, we expressed cDNA encoding amino acid residues 22 to 416 of the human thyrotropin receptor (TSHR), along with the baculovirus-encoded glycoprotein 67 signal sequence (ETSHR-gp) in insect cells. N-terminal sequence analysis revealed that the signal peptide was cleaved and confirmed the identity of ETSHR-gp protein. The molecular mass of the ETSHR-gp protein was 63 kDa and was higher than the expected molecular mass of 45 kDa, suggesting that the protein was glycosylated.

Expression of human thyrotropin in cell lines with different glycosylation patterns combined with mutagenesis of specific glycosylation sites. Characterization of a novel role for the oligosaccharides in the in vitro and in vivo bioactivity.

We used a novel approach to study the role of the Asn-linked oligosaccharides for human thyrotropin (hTSH) activity. Mutagenesis of Asn (N) within individual glycosylation recognition sequences to Gln (Q) was combined with expression of wild type and mutant hTSH in cell lines with different glycosylation patterns. The in vitro activity of hTSH lacking the Asn alpha 52 oligosaccharide (alpha Q52/TSH beta) expressed in CHO-K1 cells (sialylated oligosaccharides) was increased 6-fold compared with wild type, whereas the activities of alpha Q78/TSH beta and alpha/TSH beta Q23 were increased 2-3-fold.

Subunit-specific functions of N-linked oligosaccharides in human thyrotropin: role of terminal residues of alpha- and beta-subunit oligosaccharides in metabolic clearance and bioactivity.

The recombinant human thyroid stimulating hormone (rhTSH) containing oligosaccharides terminated with NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc beta 1 showed higher in vivo activity and lower metabolic clearance rate (MCR) than pituitary human TSH (phTSH), which contains oligosaccharides terminating predominantly in SO(4)4GalNAc(beta 1-4)GlcNAc beta 1. To elucidate the relative contribution of the sulfated and sialylated carbohydrate chains of each subunit in the MCR and bioactivity of the hormone, the alpha and beta subunits of phTSH, rhTSH, and enzymatically desialylated rhTSH (asialo-rhTSH; asrhTSH) were isolated, their oligosaccharides were analyzed, and the respective subunits were dimerized in various combinations. The hybrids containing alpha subunit from phTSH or asrhTSH showed higher in vitro activity than those with alpha subunit from rhTSH, indicating that sialylation of alpha but not beta subunit attenuates the intrinsic activity of TSH.

Asparagine-linked oligosaccharide structures determine clearance and organ distribution of pituitary and recombinant thyrotropin.

The recombinant human TSH (rhTSH) with highly sialylated oligosaccharide chains showed higher in vivo bioactivity and a lower MCR than the predominantly sulfated pituitary human TSH (phTSH). The aim of the present study was to investigate the role of terminal carbohydrate residues in organ distribution and metabolic clearance of TSH using an in vivo rat model. The different 125I-labeled TSH preparations with distinct carbohydrate composition were injected i.

Effects of continuous and pulsatile administration of pituitary rat thyrotropin and recombinant human thyrotropin in a chronically cannulated rat.

Pulsatile secretion of thyrotropin (TSH) is a well characterized phenomenon in the human, yet only limited data are available from animal studies. We propose a combined model of chronic catheterization and suppression of endogenous TSH release in the rat allowing us to apply quantified pulses of different preparations of thyrotropin intravenously with minimal interference with endogenously produced hormone. Sprague-Dawley rats treated with drinking water containing 3,5,3'-triiodothyronine (T3) showed a significant 6-fold decrease of the rat TSH (rTSH) level after four days.

A novel, nonradioactive in vivo bioassay of thyrotropin (TSH).

A new and simple in vivo bioassay suitable for routine testing of pituitary and recombinant TSH preparations was developed. Male Albino Swiss CF-1 mice were given T3 in their drinking water to suppress endogenous TSH. T3, 3.