Biomedical subjects

Vinod Nair

Publications and source records attributed to Vinod Nair.

5 recordsLinked to original sources

PubMed2004

Transdermal iontophoresis of insulin: IV. Influence of chemical enhancers.

Transdermal iontophoresis per se may not be able to achieve significant permeation of large peptides like insulin, thereby necessitating the use of combination strategies involving chemical enhancers and iontophoresis. The study investigated effect of pre-treatment with commonly used vehicles such as ethanol (EtOH), propylene glycol (PG), water and their binary combinations, dimethyl acetamide (DMA), 10% dimethyl acetamide in water, ethyl acetate (EtAc) and isopropyl myristate (IPM) on insulin iontophoresis. Solvents, which acted on the lipid bilayer, were able to produce a synergistic enhancement with iontophoresis. The binary solvent systems produced either additive or no effect, when combined with iontophoresis. FT-IR studies showed that EtOH, DMA, EtAc caused lipid extraction and the former two also caused changes in skin proteins, whereas IPM caused increase in lipid fluidity. TGA studies showed that EtOH and PG caused dehydration of skin. Skin barrier property was severely compromised with DMA, followed by EtOH and EtAc, while IPM and PG had relatively minimum skin barrier altering potential. Thus, this study demonstrates the possibility of achieving higher permeation of large peptides like insulin by combining iontophoresis with chemical enhancers that act on the intercellular lipids.

Adjuvants, Pharmaceutic↗

PubMed2004

A novel method for sequence placement of modified nucleotides in mixtures of transfer RNA.

Sequence placement of post-transcriptionally modified nucleosides in tRNA can be experimentally difficult, particularly in cases involving new or unexpected modifications or sequence sites. We describe a mass spectrometry-based approach to this problem, involving the following steps: crude isolations of one or several tRNAs by HPLC from an unfractionated tRNA mixture; digestion to oligonucleotide mixtures by RNase T1; analysis by combined HPLC/electrospray ionization-MS for recognition of modifications; and direct gas-phase sequencing of selected targets in the mixture by LC/MS/MS. Isoacceptor identity can be established in favorable cases when tRNA gene sequences are available.

Chromatography, High Pressure Liquid↗

PubMed2004

Biopharmaceutic classification system: a scientific framework for pharmacokinetic optimization in drug research.

The tenets of biopharmaceutics, solubility and permeability, are of pivotal importance in new drug discovery and lead optimization due to the dependence of drug absorption and pharmacokinetics on these two properties. A classification system for drugs based on these two fundamental parameters, Biopharmaceutic Classification System (BCS), provides drug designer an opportunity to manipulate structure or physicochemical properties of lead candidates so as to achieve better "deliverability". Considering the facts for failure of NCEs, drug research, once concentrating on optimizing the efficacy and safety of the leads, dramatically transformed in the past two decades. With the enormous number of molecules being synthesized using combinatorial and parallel synthesis, high throughput methodologies for screening solubility and permeability has gained significant interest in pharmaceutical industry. Ultimate aim of the drug discovery scientist in pharmacokinetic optimization is to tailor the molecules so that they show the features of BCS class I without compromising on pharmacodynamics. Considerations to optimize drug delivery and pharmacokinetics right from the initial stages of drug design propelled need for "High Throughput Pharmaceutics" (HTP). In silico predictions and development of theoretical profiles for solubility and lipophilicity provides structure based biopharmaceutical optimization, while in vitro experimental models (microtitre plate assays and cell cultures) validate the predictions. Thus, biopharmaceutical characterization during drug design and early development helps in early withdrawal of molecules with insurmountable developmental problems associated with pharmacokinetic optimization.

Animals↗

PubMed2003

Poloxamer gel as vehicle for transdermal iontophoretic delivery of arginine vasopressin: evaluation of in vivo performance in rats.

The present study describes the formulation and evaluation for pharmacokinetic and pharmacodynamic activity of arginine vasopressin (AVP), a nanopeptide with antidiuretic activity on being delivered by transdermal iontophoresis. Poloxamer 407 was used to form stable gels that did not reduce the release of AVP. The release rate from the gel followed Higuchi kinetics indicating that the dominant mechanism of release is diffusion. Iontophoresis alone and in combination with chemical enhancers was used to augment the transdermal permeation of AVP. The results of both pharmacokinetic and pharmacodynamic studies emphasize the dimension of 'rapid onset' achieved by iontophoresis. The correlation between pharmacokinetic data and pharmacodynamic activity was only qualitative. Histopathological studies revealed that skin toxicity caused by either iontophoresis or chemical enhancers when used alone could be reduced by using a combination of both the techniques in tandem.

Administration, Cutaneous↗

PubMed2003

Physicochemical considerations in the iontophoretic delivery of a small peptide: in vitro studies using arginine vasopressin as a model peptide.

Transdermal iontophoresis (TI) is a physical enhancement technique to facilitate the delivery of primarily charged molecules across the skin. TI of peptides is influenced by a complex interplay of several factors and one of the main issues in optimizing iontophoretic delivery of peptides is to improve the transport efficiency. From this perspective, this study investigates the effect of the physicochemical parameters on the TI of a peptide arginine vasopressin (AVP). The permeation of AVP showed a linear dependence on the concentration of drug in the donor medium. The iontophoretic flux of AVP was strongly influenced by the pH of the donor solution. Increasing the pH from 5.16 to 7.4 resulted in a decrease in the enhancement ratio by 4.5 times. When the ionic strength was increased by varying the amount of NaCl from 0.05 to 0.25 M the flux was found to decrease by 3.2 times. Replacing normal saline in the receptor compartment by HEPES buffer showed a resultant four times increase in drug permeation. The physiochemical parameters of the donor medium play a significant role in the efficiency of drug delivery by iontophoresis for a small peptide like AVP. Though electrorepulsion would be expected to be the main mechanism involved in the movement of charged molecules across the skin by iontophoresis, for peptides in the molecular weight range of AVP, other associated secondary effects like osmosis, electroosmosis and counter ion flow may also play a significant role in transport across the skin.

Administration, Cutaneous↗