Conjugation of Ibuprofen to Poly Ethylene Glycol and In-vitro drug release evaluation

Polymers have become an integral part of drug delivery systems due to their improved pharmacokinetics properties. Polymer conjugation is a well-known and widely exploited technique useful to improve therapeutic properties of peptides, proteins, small molecules and oligonucleotides. Polymer conjugated drug generally exhibit prolonged half-life, higher stability, water solubility, lower immunogenicity, antigenicity and often also to the specific targeting tissue. Polymer materials are designed to be capable of delivering active substance. to the target diseased tissues and  cells. Conjugation of Ibuprofen and polyethylene glycol (PEG) helps to increase the duration of action of the parent drug. The PEG-Ibu conjugates were synthesized from ibuprofen and PEG with two different molecular weights by esterification in the presence of DCC and DMAP. The PEG-Ibu conjugation characterized by FT-IR, UV, DSC and NMR and also in-vitro drug release study in different buffer at different ph. Keyword: Polymer, Conjugation, In vitro, prodrug, spacer molecule

Crosslinker-free collagen gelation for corneal regeneration

Development of an artificial cornea can potentially fulfil the demand of donor corneas for transplantation as the number of donors is far less than needed to treat corneal blindness. Collagen-based artificial corneas stand out as a regenerative option, having promising clinical outcomes. Collagen crosslinked with chemical crosslinkers which modify the parent functional groups of collagen. However, crosslinkers are usually cytotoxic, so crosslinkers need to be removed from implants completely before application in humans. In addition, crosslinked products are mechanically weak and susceptible to enzymatic degradation. We developed a crosslinker free supramolecular gelation strategy using pyrene conjugated dipeptide amphiphile (PyKC) consisting of lysine and cysteine; in which collagen molecules are intertwined inside the PyKC network without any functional group modification of the collagen. The newly developed collagen implants (Coll-PyKC) are optically transparent and can effectively block UV light, are mechanically and enzymatically stable, and can be sutured. The Coll-PyKC implants support the growth and function of all corneal cells, trigger anti-inflammatory differentiation while suppressing the pro-inflammatory differentiation of human monocytes. Coll-PyKC implants can restrict human adenovirus propagation. Therefore, this crosslinker-free strategy can be used for the repair, healing, and regeneration of the cornea, and potentially other damaged organs of the body

A repertoire of biomedical applications of noble metal nanoparticles

Noble metals comprise any of several metallic chemical elements that are outstandingly resistant to corrosion and oxidation, even at elevated temperatures. This group is not strictly defined, but the tentative list includes ruthenium, rhodium, palladium, silver, osmium, iridium, platinum and gold, in order of atomic number. The emerging properties of noble metal nanoparticles are attracting huge interest from the translational scientific community and have led to an unprecedented expansion of research and exploration of applications in biotechnology and biomedicine. Noble metal nanomaterials can be synthesised both by top-down and bottom up approaches, as well as via organism-assisted routes, and subsequently modified appropriately for the field of use. Nanoscale analogues of gold, silver, platinum, and palladium in particular, have gained primary importance owing to their excellent intrinsic properties and diversity of applications; they offer unique functional attributes, which are quite unlike the bulk material. Modulation of noble metal nanoparticles in terms of size, shape and surface functionalisation has endowed them with unusual capabilities and manipulation at the chemical level, which can lead to changes in their electrical, chemical, optical, spectral and other intrinsic properties. Such flexibility in multi-functionalisation delivers ‘Ockham's razor’ to applied biomedical science. In this feature article, we highlight recent advances in the adaptation of noble metal nanomaterials and their biomedical applications in therapeutics, diagnostics and sensing

A Framework for Determining Commuter Preference Along a Proposed Bus Rapid Transit Corridor

Study of commuters ‘attitude towards public transport and their perceptions of existing service quality for different service attributes of public transport have gained immense importance in recent years for determining appropriate public transport service levels so as to retain the loyalty of existing users and for attracting potential users. Commuters ‘perception of service quality varies for different service delivery environments due to different urban settings, i.e., land use and traffic system, location and route characteristics, level of accessibility, fare structure, past experiences from service providers and their assessment of what is possible to be delivered. While, Level-of-Service (LOS) is a general measure to determine good, poor and acceptable service levels for various service attributes of public transport based on user perception, there is a further need to determine the minimum and maximum tolerance level of users i.e., the zone of tolerance (ZOT) and the percentage of users satisfied at different service levels which is defined here as ‘user satisfaction level (USL)’ for different service attributes at the route or corridor level to determine commuters’ needs and preferences for that particular route/corridor which may differ significantly from other routes/corridors within the city. In addition, to ZOT and USL, it is also equally important to identify the critical service areas which need immediate improvement based on commuter preference. The present research proposes a framework to determine commuter preference for different service attributes of existing bus routes along a major corridor which could help in designing service levels for a proposed bus rapid transit (BRT) corridor

Methodology to determine service delivery levels for public transportation

When designing transit services, the Level-of-Service concept has been widely used by transport planners and service providers to assess the service quality of an existing transit system. In addition to the service quality assessment, service providers also need to estimate the service levels that will satisfy a maximum number of users and potential users, across all socio-economic groups, so as to maximize patronage. This paper demonstrates a method using the concept of ‘user satisfaction levels’ and their ‘zone of tolerance’, along with total utility and marginal utility for service providers, to provide a range of service delivery levels for individual transit service attributes in the city of Kolkata. This range of service levels provides a guideline for service providers within which they can consider making an improvement in service level. However, the final decision on service improvement is an outcome of both financial and infrastructural feasibility

Importance of user perception in evaluating level of service for bus transit for a developing country like India: a review

Assessment of service quality in bus transit planning has received due attention in recent years from the viewpoint of optimal service allocation. The concept of level of service (LOS) has emerged as an effective tool to measure quality of services. Service-quality assessment provides operators with knowledge on users\u27 satisfaction with existing services and their expected LOSs. The importance of user perception towards assessment of LOS has been acknowledged by researchers. While LOS standards for public transportation have been established by the Transportation Research Board in the USA, researchers have questioned the applicability of these standards in the context of different geographic regions. Since the service delivery environment differs between developed and developing nations, the user perception of service quality varies between these economic regions. Substantial research has been carried out in the context of both developed and developing nations, to identify the bus transit service parameters that affect users\u27 perceived service quality; however, little research exists that establishes LOS thresholds for bus transit, based on user perception. This paper reviews the concept of LOS, describes the importance of user perception in assessment of service quality and identifies the need to establish LOS thresholds for bus transit from user perception for developing countries

Improving the lipase activity profile in cationic water-in-oil microemulsions of hydroxylated surfactants

The activity of Chromobacterium viscosum lipase (CV-lipase) in cationic water-in-oil (w/o) microemulsions is significantly lower compared to that in bis(2-ethylhexyl)sulfosuccinate sodium salt (AOT)-based (anionic) systems. 26,36,38,39In the present study, we estimated the second-order rate constants k2 in lipase-catalyzed hydrolysis of p-nitrophenylcaproate, in newly developed cationic w/o microemulsions of synthesized surfactants (2−6, Chart 1) containing hydroxyethyl moieties at the polar headgroup. The kinetic studies at pH = 6.0 (pH refers to the pH of the aqueous buffer solutions used in preparing the w/o microemulsions) show that the catalytic efficiency of CV-lipase was systematically increased with the sequential increment of hydroxyethyl groups at the polar heads of surfactants (1−4, Chart 1), possibly due to the increase in the interfacial concentration of water [H2O] i in consequence of the added hydrogen bonding ability of hydroxyl groups. To this end, we found that in a 0.05 M 4/water/32.3:1 (v/v) isooctane/n-hexanol w/o microemulsion, the activity of lipase is almost 4-fold higher than that in 0.05 M cetyltrimethylammonium bromide (CTAB)/water/9:1 (v/v) isooctane/n-hexanol37 systems and is enhanced by an order of magnitude compared to that in the case of CTAB/water/heptane−chloroform (1:1, v/v) w/o microemulsions. 26Moreover, to our knowledge, the observed k2 is the highest-ever lipase activity, hitherto unattainable in any cationic w/o microemulsion. Simultaneously, for the first time, the estimated activity of lipase in the former cationic w/o microemulsion is akin to the best-ever activity of lipase found in a w/o microemulsion of AOT. 26In addition, the pH profile and the stability of CV-lipase were investigated in newly developed w/o microemulsions

Improved activity of enzymes in mixed cationic reverse micelles with imidazolium-based surfactants

This work reports the significant enhancement in performance of interfacially active enzymes, Chromobacterium viscosum (CV) lipase and horseradish peroxidase (HRP) in mixed reverse micelles of cetyltrimethylammonium bromide (CTAB) and imidazolium-based amphiphiles having varying tail lengths. Lipase activity in these mixed systems was always higher than that in the individual cationic reverse micelles of CTAB or any imidazolium surfactant, highest being observed in the mixed system of CTAB (50 mM) and 6 (1-tetradecyl-3-methyl imidazolium bromide, 40 mM)/water/isooctane/n-hexanol (0.24 M), second-order rate constant, k<SUB>2</SUB> = 1301 ± 5 cm<SUP>3</SUP> g<SUP>-1</SUP> s<SUP>-1</SUP>, ∼200% higher compared to that in CTAB and ∼65% more than the most popular AOT-microemulsion. Activity increased with concentration of imidazolium surfactant and also with its alkyl tail length. To have a more profound view on the structure–activity relationship, CTAB was replaced by cetyltriethylammonium bromide (CTEAB) and cetyltripropylammonium bromide (CTPAB) with subsequent increase in the headgroup size. The generalized influence of these mixed cationic systems on surface-active enzyme was also verified using HRP, where the activity improved ∼100%. This enhancement in enzyme activity is presumably due to the activating effect of the imidazolium cation in the enzymatic reactions by improving the nucleophilicity of interfacial water in vicinity of enzyme through hydrogen bonding

Probing the relationship between interfacial concentrations and lipase activity in cationic W/O microemulsions: a quantitative study by chemical trapping

Interfacial concentrations and/or space:  which one is the predominant factor in regulating lipase activity at the water−oil interface? This work is an endeavor toward probing the relationship between lipase activity and interfacial concentrations in cationic water-in-oil (W/O) microemulsions through quantitative study by a chemical trapping method. The interfacial concentrations of water ([H2Oi]), bromide ([Bri-]), and n-hexanol ([HexOHi]) were estimated in the W/O microemulsions of six surfactants with varying headgroup architecture and hydrophilicity across a wide Wo ([H2O]/[surfactant]) range. The surfactants were prepared by the replacement of methyl groups of cetyltrimethylammonium bromide (1) by n-propyl (2−4), one hydroxyethyl (5), and one methoxyethyl (6) group. The estimated [H2Oi] was found not to change much (30.0−36.7 M) with the variation in headgroup hydrophilicity or size from 1−5. However, [Bri-] was found to increase with a decrease in the degree of dissociation (α), being higher for 1 and 5 (2.4−3.3 M) and relatively lower (0.9−1.9 M) for others depending on Wo. Interestingly, [H2Oi] was found to be little higher (41.5−42.2 M) in the case of 6. The present study elucidates the importance of interfacial water and counterion concentrations in modulating the lipase activity in reverse micelles. In our previous report, the lipase activity was found to increase from 1−4 and in 6, whereas that observed in 5 was comparable with 1, being largely regulated by the surfactant head group size (Das, D.; Roy, S.; Mitra, R. N.; Dasgupta, A.; Das, P. K. Chem. Eur. J. 2005, 11, 4881). The only other parameter that increased distinctly with lipase activity is the headgroup size, not [H2Oi]. Thus, the role of [H2Oi] in comparison to the surfactant's headgroup size is not found to be that significant. Moreover, the lower [Bri-] in 2−4 and 6 perhaps enhances the probability of enzyme and substrate localization at the interface, leading to higher lipase activity

Aggregation-Induced Emission or Hydrolysis by Water? The Case of Schiff Bases in Aqueous Organic Solvents

In the last two decades, several Schiff bases have been reported as AIEgens which remain nonemissive in organic solvents but show strong fluorescence in the presence of water. A methodical analysis involving 21 Schiff bases, including some of the reported molecules, shows that in the presence of water, the Schiff bases hydrolyze to yield the corresponding starting aldehydes and amines. The observed emission in the presence of water is found to be originated from the aggregation of the fluorogenic aldehydes and not of the original molecules. Thus, while the aggregation-induced emission (AIE) effect is valid for these systems, certainly, these Schiff bases cannot be termed as AIEgens. Notably, the observation that these aldehydes can act as AIEgens through their excimer emission is an important phenomenon with respect to the current understanding of AIEgens