Effect of the average soft-segment length on the morphology and properties of segmented polyurethane nanocomposites

Two organically modified layered silicates (with small and large diameters) were incorporated into three segmented polyurethanes with various degrees of microphase separation. Microphase separation increased with the molecular weight of the poly(hexamethylene oxide) soft segment. The molecular weight of the soft segment did not influence the amount of polyurethane intercalating the interlayer spacing. Small-angle neutron scattering and differential scanning calorimetry data indicated that the layered silicates did not affect the microphase morphology of any host polymer, regardless of the particle diameter. The stiffness enhancement on filler addition increased as the microphase separation of the polyurethane decreased, presumably because a greater number of urethane linkages were available to interact with the filler. For comparison, the small nanofiller was introduced into a polyurethane with a poly(tetramethylene oxide) soft segment, and a significant increase in the tensile strength and a sharper upturn in the stress-strain curve resulted. No such improvement occurred in the host polymers with poly(hexamethylene oxide) soft segments. It is proposed that the nanocomposite containing the more hydrophilic and mobile poly(tetramethylene oxide) soft segment is capable of greater secondary bonding between the polyurethane chains and the organosilicate surface, resulting in improved stress transfer to the filler and reduced molecular slippage. (c) 2006 Wiley Periodicals, Inc.

Community paediatrics: Soft science or firm foundations?

Community paediatrics strives to integrate the biology of health into the social and psychological worlds within which children grow and develop. Consumer demand for limited community paediatric clinical services is increasing and medico-legal pressures escalate professional and personal concern. Meanwhile, the profession, through training and professional support, has struggled to keep up. Research into community paediatrics and its integration into policy and clinical practice remains limited, raising the perception that it is a 'soft' science. Our viewpoint is that necessary progress in this field requires leadership, apprenticeship and research. We argue that to build firm foundations for the future requires structures to enable clinical specialisation and continuing professional development in this area.

Simplified recording of soft contact lens fit

Purpose: To determine the critical fitting characteristics of modern soft contact lens fits and from this to devise a simplified recording scheme. Methods: Ten subjects (aged 28.1 ± 7.4 years) wore eight different modern soft contact lenses. Video was captured and analysed of blink (central and up-gaze), excursion lag (up, down, right and left gaze) and push-up movement, centration and coverage. Results: Lens centration was on average close to the corneal centre. Movement on blink was significantly smaller in up-gaze than in primary-gaze (p<0.001). Lag was greatest in down-gaze and least in up-gaze (p<0.001). Push-up test recovery speed was 1.32±0.73mm/s. Overall lens movement was determined best by assessing horizontal lag, movement on blink in up-gaze and push-up recovery speed. Steeper lens base-curves did not have a significant effect on lens fit characteristics. Contact lens material did influence lens fit characteristics, particularly silicone-hydrogels which generally had lower centration and a faster push-up speed of recovery than HEMA lenses (p<0.05). Conclusion: Lag on vertical gaze, and movement on blink in primary gaze generally provide little extra information on overall lens movement compared to horizontal lag, movement on blink in up gaze and push-up recovery speed. They can therefore be excluded from a simplified recording scheme. A simplified and comprehensive soft contact lens fit recording system could consist of a cross-hairs indicating the centre of the cornea; a circle to indicate the lens centration; a mark on the relevant position of the circle to indicate any limbal incursion; a grade (‘B’) below for movement with blink in up-gaze, a grade (‘L’) to the side for horizontal lag and a grade above (‘P’) for the assessed push-up recovery speed.

The influence of corneoscleral topography on soft contact lens fit

To evaluate the influence of peripheral ocular topography, as evaluated by optical coherence tomography (OCT), compared with traditional measures of corneal profile using keratometry and videokeratoscopy, on soft contact lens fit.

Objective clinical performance of ‘comfort-enhanced' daily disposable soft contact lenses

Purpose: To examine the objective clinical performance of ‘comfort-enhanced’ daily disposable contact lenses over a 16-h day. Methods: Four contact lenses (Hilafilcon B, Etafilcon A Plus, Nelfilcon A and Nelfilcon A Plus) were evaluated in an investigator masked, open label trial at the end of a week’s bilateral wear. Pre-lens noninvasive tear break-up time (PL-NITBUT), tear prism height, bulbar hyperaemia and ocular surface temperature (OST) were measured with the lens in situ at 8, 12 and 16 h of wear. Results: There was no difference between how many hours the lenses types were worn each day (F = 0.90, p = 0.44). The PL-NITBUT decreased with the duration of daily lens wear (F = 32.0, p < 0.001) and was more stable with Nelfilcon A Plus (F = 6.00, p = 0.002) than with the other lenses evaluated. Bulbar blood vessels increased in coverage (F = 11.5, p < 0.001) but not overall redness (F = 0.0, p = 0.99) with the duration of daily lens wear, but there was no difference between the lenses (p > 0.05). The tear prism height decreased with the duration of daily wear (F = 27.0, p < 0.001) and differed between lenses (F = 2.9, p = 0.04). The OST decreased with the duration of lens wear (F = 119.7, p < 0.001) and was reduced by daily disposable lens wear (F = 7.88, p < 0.001), but did not differ between lenses (F = 0.88, p = 0.45). Conclusions: Objective measures of tear film indicated a difference between the lenses evaluated for PLNITBUT and tear prism height, but not for wearing time or bulbar conjunctival hyperaemia. Therefore clinical benefits of daily disposable ‘comfort enhancing’ contact lenses can be measured, but challenges remain in producing contact lenses that do not compromise anterior eye physiology over the whole day. 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Soft hydrogels from nanotubes of poly(ethylene oxide)−tetraphenylalanine conjugates prepared by click chemistry

A new poly(ethylene oxide)-tetraphenylalanine polymer-peptide conjugate has been prepared via a “click” reaction between an alkyne-modified peptide and an azide-terminated PEO oligomer. Self-assembled nanotubes are formed after dialysis of a THF solution of this polymer-peptide conjugate against water. The structure of these nanotubes has been probed by circular dichroism, IR, TEM, and SAXS. From these data, it is apparent that self-assembly involves the formation of antiparallel ß-sheets and p-p-stacking. Nanotubes are formed at concentrations between 2 and 10 mg mL-1. Entanglement between adjacent nanotubes occurs at higher concentrations, resulting in the formation of soft hydrogels. Gel strength increases at higher polymer-peptide conjugate concentration, as expected.

Analytical techniques for the study of soft contact lens spoilation

Soft contact lens wear has become a common phenomenon in recent times. The contact lens when placed in the eye rapidly undergoes change. A film of biological material builds up on and in the lens matrix. The long term wear characteristics of the lens ultimately depend on this process. With time distinct structures made up of biological material have been found to build up on the lens. A fuller understanding of this process and how it relates to the lens chemistry could lead to contact lenses that are better tolerated by the eye. The tear film is a complex biological fluid, it is this fluid that bathes the lens during wear. It is reasonable to suppose that it is material derived from this source that accumulates on the lens. To understand this phenomenon it was decided to investigate the make up and conformation of the protein species that are found on and in the lens. As inter individual variations in tear fluid composition have been found it is important to be able to study the proteins on a single lens. Many of the analytical techniques used in bio research are not suitable for this study because of the lack of sensitivity. Work with poly acrylamide electrophoresis showed the possibility of analyzing the proteins extracted from a single lens. The development of a biotin avidin electro-blot and an enzyme linked aniibody electro-blot, lead to the high sensitivity detection and identification of the proteins present. The extraction of proteins from a lens is always incomplete. A method that analyses the proteins in situ would be a great advancement. Fourier transform infra red microscopy was developed to a point where a thin section of a contact lens could yield information about the proteins present and their conformation. The three dimensional structure of the gross macroscopic structures termed white spots was investigated using confocal laser microscopy.

Soft [beta]-adrenoceptor agonists for topical use in psoriasis

Psoriasis is characterised by epidermal proliferation and inflammation resulting in the appearance of elevated erythematous plaques. The ratio of c~AMP/c~GMP is decreased in psoriatic skin and when the epidermal cell surface receptors are stimulated by β-adrenergic agonists, intracellular ATP is transformed into c-AMP, thus restoring the c~AMP/c~GMP levels. This thesis describes a series of β-adrenoceptor agonists for topical delivery based upon the soft-drug approach. Soft drugs are defined as biologically active, therapeutically useful chemical compounds (drugs) characterised by a predictable and controllable In vivo destruction (metabolism) to non-toxic moieties. after they achieve their therapeutic role, The N-substituent can accommodate a broad range of structures and here the alkoxycarbonylethyl group has been used to provide metabolic susceptability. The increased polarity of the dihydroxy acid, expected after metabolic conversion of the soft~drug, ethyl N-[2'-(3',4'-dihydroxyphenyl)-2'-hydroxyethyl]-3- aminopropionate, should eliminate agonist activity. Further. to prevent oxidation and enhance topical delivery, the catechol hydroxyl groups have been esterified to produce a pro-soft-drug which generates the soft-drug in enzymic systems. The chemical hydrolysis of the pro-soft-drug proceeded via the formation of the dlpivaloyloxy acid and it failed to generate the active dihydroxy ester soft-drug. In contrast, in the presence of porcine liver carboxyesterase, the hydrolysis of the pro-soft drug proceeded via the formation of the required active soft-drug. This compound, thus, has the appropnate kinetic features to enable it to be evaluated further as a drug for the treatment of psoriasis. The pH rate-profile for the hydrolysis of soft-drug indicated a maximum stability at pH ∼ 4.0. The individual rate constants for the degradation and the pKa were analysed by nonlinear regression. The pKa of 7.40 is in excellent agreement with that determined by direct titration (7.43) and indicates that satisfactory convergence was achieved. The soft-drug was poorly transported across a silicone membrane; it was also air-sensitive due to oxidation of the catechol group. The transport of the pro-soft-drug was more efficient and, over the donor pH range 3-8, increased with pH. At lower values, the largely protonated species was not transported. However, above pH 7. chemical degradation was rapid so that a donor pH of 5-6 was optimum. The β-adrenergic agonist activity of these compounds was tested in vitro by measuring chronotropic and inotropic responses in the guinea pig atria and relaxation of guinea pig trachea precontracted with acetylcholine (10-3 M). The soft~drug was a full agonist on the tracheal preparation but was less potent than isoprenaline. Responses of the soft~drug were competitively antagonised by propranolol (10-6 M). The soft~drug produced an increase in force and rate of the isolated atrial preparatIon. The propyl analogue was equally potent with ED50 of 6.52 x 10-7 M. In contrast, at equivalent doses, the dihydroxy acid showed no activity; only a marginal effect was observed on the tracheal preparation. For the pro~soft-drug, responses were of slow onset, in both preparations, with a slowly developing relaxatlon of the tracheal preparatlon at high concentrations (10-5 M). This is consistent with in vitro results where the dipivaloyl groups are hydrolysed more readily than the ethyl ester to gIve the active soft-drug. These results confirm the validity tif the pro-soft-drug approach to the deUvery of β-adrenoceptor agonists.