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Biomedical subjects

Indu Pal Kaur

Publications and source records attributed to Indu Pal Kaur.

11 recordsLinked to original sources

Development and evaluation of sesamol as an antiaging agent.

Aging comprises various changes that occur in living organisms with the passage of time, leading to increased system entropy, loss of homeostasis and eventually death. Of the various theories proposed, the free radical theory of aging states that it is the shift in antioxidant/pro-oxidant balance that leads to increased oxidative stress, dysregulation of cellular function and aging. It has been proved that accumulated damage by free radicals produced by exposure to ultraviolet (UV) radiation results in extensive damage to the soft skin tissues, which is commonly known as "photoaging". Although the human body has built-in antioxidant mechanisms to suppress uncontrolled free radicals, these mechanisms may at times fail due to overwhelming production of toxic radicals. This is where supplemental antioxidants can play a vital role in restoring the balance, lack of which produces visible wrinkling and premature aging. Sesamol, a highly acclaimed antioxidant, was selected as a suitable antioxidant to investigate in this study, and is for the first time shown to counter UV-induced oxidative stress (in terms of both biochemical and histopathological changes) in mouse skin. The source of radiation was a 300-W UV lamp, and mice of the lacca strain were chosen as an animal model for this study. Free radical levels generated were estimated using the Ohkawa method for estimation of lipid peroxidation in animal tissues. The results from biochemical and histopathological investigations clearly confirm that the sesamol formulation is effective in preventing photodamage (lesions, ulcers and changes in skin integrity) due to chronic UV exposure.

Administration, Topical↗

Screening methods for antioxidants-a review.

Various environmental, physical and chemical stresses on cells may induce either an overproduction of ROS (Reactive Oxygen Species) or a deficiency of antioxidant enzymes. ROS are responsible for various cellular anomalies like protein damage, deactivation of enzymes, alteration of DNA and lipid peroxidation which in turn leads to pathological conditions like carcinogenesis, reperfusion injury, rheumatoid arthritis, diabetes etc. The regular intake of antioxidants seems to limit or prevent the dangerous effects caused by ROS. Thus, to maintain cellular health, it is important to have a specific and effective antioxidant that scavenges multiple types of free radicals so that it can be used in multiple diseases. Different in vitro and in vivo test systems are available in the literature to assess the free radical scavenging activity of various compounds. Based on the efficiency of free radical scavenging, the compounds are classified into strong, moderate and weak antioxidants. The following review explains the brief procedure and the principle behind various methods available in the literature, which can be used to determine the scavenging of different types of free radicals.

Animals↗

Ginseng extract exhibits antimutagenic activity against induced mutagenesis in various strains of Salmonella typhimurium.

Ginseng has been reported to exhibit antioxidant and antimutagenic activity. The present study was undertaken with a view to confirm whether the antioxidant activity of Ginseng is responsible for its antimutagenic action. The concentrated root extract of Panax ginseng (Ginseng extract I) and its lyophilized powder (Ginseng extract II) obtained from two different manufacturing houses, were tested against mutagenesis using the well-standardized Ames microsomal test system. The extracts exhibited antimutagenic effect against hydrogen peroxide induced mutagenesis in TA100 strain, and against mutagenesis produced by 4-nitroquinoline-N-oxide in both TA98 and TA100 strains of Salmonella typhimurium. Both the extracts failed to show any antimutagenic potential against tert-butyl hydroperoxide (an oxidative mutagen) in TA102 strain, a strain highly sensitive to active oxygen species. The extracts also indicated a weak antioxidant activity in a series of in vitro test systems viz., 1,1-diphenyl picryl hydrazyl (DPPH) assay, hydrogen peroxide scavenging and superoxide anion scavenging. The results indicate that the protective effects shown by ginseng extract(s) against 4-nitroquinoline-n-oxide and hydrogen peroxide induced mutagenesis in TA98 and TA100 could mainly be due to its property to initiate and promote DNA repair rather than free radical scavenging action.

Antimutagenic Agents↗

Antimutagenic and antioxidant/prooxidant activity of quercetin.

The present study has been performed to evaluate the antimutagenic activity of quercetin, ascorbic acid and their combination against an oxidative mutagen. An effort was also made to correlate this activity to the in vitro antioxidant activity of these agents. Antimutagenicity testing was done in Ames Salmonella Assay system using Salmonella typhimurium TA102 against t-butylhydroperoxide as an oxidative mutagen. In vitro antioxidant scavenging activity was tested for DPPH free radical, superoxide anion, hydrogen peroxide and hydroxyl radical in their specific test systems. Quercetin (0.5-8 nmole/plate) and ascorbic acid (0.1-100 micromole/plate) showed significant effect. Quercetin (4 and 8 nmole/plate) when combined with ascorbic acid (500 nmole/plate) showed an increase in the antimutagenic activity. In vitro antioxidant activity of quercetin was better than ascorbic acid in all the test systems used. The study indicated that the antimutagenic activity of quercetin was not solely accountable by its antioxidant nature. However, in vitro free radical scavenging activity of quercetin correlated well with the antimutagenic activity.

Antimutagenic Agents↗

Delineation of antimutagenic activity of catechin, epicatechin and green tea extract.

Tea is consumed worldwide as second largest to water in popularity as a beverage. It has been reported that tea extracts have antibacterial, antiviral, antioxidative, antitumor and antimutagenic activities. The protective effect of green tea has been assumed to be due to the powerful scavenging and antioxidative property of high concentrations of unpolymerised catechins and their gallates. In the present proposal green tea extract (GT), (+)-catechin (C) and (-)-epicatechin (EC) were investigated for their antioxidant activity by different in vitro methods like (i) DPPH assay (ii) superoxide anion scavenging and (iii) hydrogen peroxide scavenging activity. Further these agents were also tested against mutagenesis using the well-standardized Ames microsomal test system. The Ames tester strain Salmonella typhimurium TA102, which readily responds to reactive oxygen species, was used and the antimutagenic activity was evaluated against oxidative mutagens tertiary butyl hydroperoxide (ID50-24.41, 29.63 and 113.23 microg for EC, C and GT, respectively) and hydrogen peroxide (ID50-17.3, 18.4 and 88.1 microg for EC, C and GT, respectively). Ascorbic acid was used as a standard antioxidant in all the experiments. Results indicate that all the three agents possess excellent DPPH free radical scavenging activity (IC50-1.5 microg for EC, 3.45 microg for C and 3.8 microg for GT), good hydrogen peroxide (IC50-11.18 microg for EC, 13.5 microg for C and 11.78 microg for GT) and superoxide anion scavenging (IC50-1.64 microg for EC, 1.74 microg for C and 3.52 microg for GT) activities. Further, they also show antimutagenic activity in the above-mentioned test systems establishing their antioxidant nature to be responsible for such activity. The in vitro antioxidant activity correlates well with the antimutagenic action. (-)-Epicatechin is indicated to be a better agent in comparison to the other two agents (ID50-1.2 times more than C and 5 times more than GT in antimutagenicity studies against t-BOOH and hydrogen peroxide induced mutagenesis). Ascorbic acid however showed a much less activity (ID50-12.1 mg against t-BOOH and 7.2 mg with hydrogen peroxide induced mutagenesis).

Antimutagenic Agents↗

Role of cyclodextrins in ophthalmics.

Cyclodextrins are oligosaccharides having outer hydrophilic surface and central hydrophobic cavity. These agents form inclusion complexes with poorly water-soluble drugs; hence they show an important implication for use in ophthalmics because of their applications in solubilising and stabilising the ocular drugs. Most of the drugs being used in ophthalmics were not tailor-made for the eye and considering the poor bioavailability of <1% from the corneal surface, presentation of the drug in a soluble form and at high concentration is important. Provision of a high drug concentration at the corneal surface increases the percent drug permeation indicating the usefulness of cyclodextrins as penetration enhancers. A decrease in irritation potential of some drugs upon incorporation of cyclodextrins is also reported. Polymer-cyclodextrin multicomponent systems further extend the role of cyclodextrins in improving the solubility and bioavilability of ocular drugs. Large hydrophilic cyclodextrins like hydroxypropyl-beta-cyclodextrin and sulphobutylether-beta-cyclodextrin are safe for the use in aqueous eye drop solutions especially since they do not cross the lipophilic cornea. Various aspects about the applications of cyclodextrins in ophthalmics, the formulation considerations and expected toxicity of cyclodextrins (especially if high concentration is used) is discussed in this review. Strategies like use of polymers to reduce the effective concentration of cyclodextrin required without compromising solubility are also included. Further the concept of incorporating the drug-cyclodextrin complexes into liposomes or niosomes for a better targeting of the drug at appropriate tissue destination is discussed as a possible future option.

Chemistry, Pharmaceutical↗

Development of topically effective formulations of acetazolamide using HP-beta-CD-polymer co-complexes.

The myriad of side effects induced by acetazolamide (oral use), the introduction of newer topical carbonic anhydrase inhibitors (CAI's) and the advent of other antiglaucoma medications has led to a decreased interest in acetazolamide. The use of cyclodextrins to improve the solubility and bioavailability of poorly soluble drugs has however, rekindled an interest in acetazolamide (ACZ), because its poor solubility is one of the major factor responsible for its failure to show topical effectiveness. Since water soluble polymers have been reported to improve the complexing capabilities of beta-cyclodextrins, in the present study water soluble polymers like polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), hydroxypropymethylcellulose (HPMC) and the mucoadhesive polymer Carbopol 934P were incorporated into aqueous 10% w/v 2HP-beta-CD solution to improve the solubility of ACZ. The effect of these polymers on the corneal transport of 5 mg/ml (0.5% w/v) solution of ACZ in aqueous 10% 2HP-beta-CD was evaluated. The inclusion of these polymers significantly increased the solubility of ACZ from 3.43 mg/ml in aqueous 10% 2HP-beta-CD to 5.1 mg/ml (48.6%) in 0.05% PVP; 6.80 mg/ml (98.3%) in 0.05% PVA; and 6.74 mg/ml (96.5%) in 0.2% Carbopol 934P. From amongst the various polymers assessed in the study, PVA was deemed the best, based on the premise of better apparent permeability coefficient (P(app)) upon in vitro corneal permeation studies. Inspite of a large enhancement in solubility produced by Carbopol 934P, surprisingly, it could not efficiently increase the Papp.

2-Hydroxypropyl-beta-cyclodextrin↗

Acetazolamide: future perspective in topical glaucoma therapeutics.

Through this review it is contemplated that acetazolamide (ACZ), an age-old treatment for glaucoma with a myriad of side effects and inadequate topical effectiveness, may be formulated into a topically effective agent by utilizing various newer formulation approaches of ocular drug delivery. Even though it has a poor solubility and penetration power, various studies mentioned in the review indicate that it is possible to successfully formulate topically effective ACZ by using: (i) high concentration of the drug, (ii) surfactant gel preparations of ACZ, (iii) ACZ loaded into liposomes, (iv) cyclodextrins to increase the solubility and hence bioavailability of ACZ, and (v) viscolyzers and other polymers either alone or in combination with cyclodextrins. With the advent of newer topical carbonic anhydrase inhibitors (CAIs) like dorzolamide and brinzolamide, a localized effect with fewer side effects is expected. But whenever absorbed systemically, a similar range of adverse effects (attributable to sulphonamides) may occur upon use. Furthermore, oral ACZ is reported to be more physiologically effective than 2% dorzolamide hydrochloride administered topically, even though in isolated tissues dorzolamide appears to be the most active as it shows the lowest IC(50) values for CA-II and CA-IV [M.F. Surgue, J. Ocular Pharmacol. Ther. 12 (1996) 363-376]. Hence, there exists considerable scope for the development of more/equally effective and inexpensive topically effective formulations of ACZ. The use of various formulation technologies discussed in this review can provide a fresh impetus to research in this area.

Acetazolamide↗

Probiotics: potential pharmaceutical applications.

Realisation of the importance of human gut microbiota in health restoration and maintenance has kindled an interest in probiotics. Probiotics are defined as the microbial food supplements, which beneficially affect the host by improving its intestinal microbial balance. Probiotics are the health enhancing functional food ingredients used therapeutically to prevent diarrhea, improve lactose tolerance and modulate immunity. They may also have potential to prevent cancer and lower serum cholesterol levels. Lactobacillus, Bifidobacterium and several other microbial species are perceived to exert such effects by changing the composition of the gut microbiota. However, it is important that exogenously administered bacteria reach and establish themselves in the large intestine in an intact form. The use of non-digestible oligosaccharides ('prebiotics') can fortify intestinal microflora and stimulate their growth. The present review encompasses information regarding the probiotics and their proposed uses. It addresses the concepts of prebiotics and synbiotics, the application of genetic engineering to produce newer probiotics. Finally, the list of commercially available products are reviewed with discussion of questions regarding the reliability, utility and the safety of these products.

Animals↗

Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic drug delivery.

This review is focused on the two avenues of development that promise a major impact on future ocular drug therapeutics: bioadhesives, including hydrogels and other agents like carbopols, polyacrylic acids, chitosan, etc., and penetration enhancers, including different surfactants, calcium chelators, etc. The capacity of some polymers to adhere to the mucin coat covering the conjunctiva and the corneal surface of the eye forms the basis for ocular mucoadhesion. These systems markedly prolong the residence time of a drug in the conjunctival sac, since clearence is now controlled by the much slower rate of mucus turnover rather than the tear turnover rate. But improving the corneal drug retention alone is inadequate in bringing about a significant improvement of drug bioavailability. Another approach consists of transiently increasing the pentration characteristics of the cornea with appropriate substances, known as penetration enhancers or absorption promoters. The main aim of this article is to give an insight into the potential application of mucoadhesives and corneal penetration enhancers for the conception of innovative opthalmic delivery appraoches, to decrease the systemic side effects, and create a more focused effect, which may be achieved with lower doses of the drug. Ophthalmic formulations based on these mucoadhesives and penetration enhancers are simple to manufacture and exhibit an excellent tolerance when administered into the cornea. The use of the former considerably prolongs the corneal contact time and the use of the latter increases the rate and amount of drug transport. The various corneal epithelial barriers along with the major routes of transport of drugs are discussed. The article includes a list of the various substances in use or under investigation for the aforementioned properties, along with their mechanisms of action. A fair appraisal of the subject with regard to these two therapeutic approaches and any expected ill effects has been made.

Adhesives↗

Ocular preparations: the formulation approach.

The main aim of pharmacotherapeutics is the attainment of an effective drug concentration at the intended site of action for a sufficient period of time to elicit the response. A major problem being faced in ocular therapeutics is the attainment of an optimal concentration at the site of action. Poor bioavailability of drugs from ocular dosage forms is mainly due to the tear production, non-productive absorption, transient residence time, and impermeability of corneal epithelium. This article reviews: (1) the barriers that decrease the bioavailability of an ophthalmic drug; (2) the objectives to be considered in producing optimal formulations; and (3) the approaches being used to improve the corneal penetration of a drug molecule and delay its elimination from the eye. The focus of this review is on the recent developments in topical ocular drug delivery systems, the rationale for their use, their drug release mechanism, and the characteristic advantages and limitations of each system. In addition, the review attempts to give various analytical procedures including the animal models and other models required for bioavailability and pharmacokinetic studies. The latter can aid in the design and predictive evaluation of newer delivery systems. The dosage forms are divided into the ones which affect the precorneal parameters, and those that provide a controlled and continuous delivery to the pre- and intraocular tissues. The systems discussed include: (a) the commonly used dosage forms such as gels, viscosity imparting agents, ointments, and aqueous suspensions; (b) the newer concept of penetration enhancers, phase transition systems, use of cyclodextrins to increase solubility of various drugs, vesicular systems, and chemical delivery systems such as the prodrugs; (c) the developed and under-development controlled/continuous drug delivery systems including ocular inserts, collagen shields, ocular films, disposable contact lenses, and other new ophthalmic drug delivery systems; and (d) the newer trends directed towards a combination of drug delivery technologies for improving the therapeutic response of a non-efficacious drug. The fruitful resolution of the above-mentioned technological suggestions can result in a superior dosage form for both topical and intraocular ophthalmic application.

Absorption↗