BackgroundSustained drug delivery is a large unmet clinical need in glaucoma. Here, we incorporated a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor, CCG-222740, into slow release large unilamellar vesicles derived from the liposomes DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), and tested their effects in vitro and in vivo.ResultsThe vesicles were spherical particles of around 130 nm and were strongly cationic. A large amount of inhibitor could be incorporated into the vesicles. We showed that the nanocarrier CCG-222740 formulation gradually released the inhibitor over 14 days using high performance liquid chromatography. Nanocarrier CCG-222740 significantly decreased ACTA2 gene expression and was not cytotoxic in human conjunctival fibroblasts. In vivo, nanocarrier CCG-222740 doubled the bleb survival from 11.0 ± 0.6 days to 22.0 ± 1.3 days (p = 0.001), decreased conjunctival scarring and did not have any local or systemic adverse effects in a rabbit model of glaucoma filtration surgery.ConclusionsOur study demonstrates proof-of-concept that a nanocarrier-based formulation efficiently achieves a sustained release of a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor and prevents conjunctival fibrosis in an established rabbit model of glaucoma filtration surgery.

The pursing of a simply-or doubly-connected planar elastic pocket by an applied pressure is analysed from the bending to the stretching regimes. The response is evaluated in terms of maximum deflection and profiles across a range of simply-and doubly-connected circular and square shapes. The study is conducted using experimental and numerical methods and supported by previous analytical results. The experimental method is based on an original 2D optical method that gives access to the pursing direction perpendicular to each image across the field of view. The equations for maximum pursing deflections are developed and compared for a range of thicknesses of silicone samples and shapes from the bending to the stretching regimes. In the case of doubly-connected shapes, dependence of maximum pursing deflection on clamped central circular and square areas or holes is quantified for both regimes. Good agreement is established between the three methods and the study also shows that the optical method may as well be successfully applied to problems of pursing of rubber pockets.

A circular silicone sheet is clamped at its edge and pressurised by the injection of a liquid beneath creating a pocket. We study experimentally the deformation and pressure increase caused by the compression of a pressurised pocket. Excellent agreement is found between experimental observations and numerical predictions based on an axisymmetric thin hyperelastic material; an approximate analytical model explains the link between changes in shape and the applied force.

Taste is most important organoleptic aspects about the acceptance of oral drugs. Bitter and unpalatable taste is a major problem of certain drugs in formulations. In market, there are numbers of pharmaceutical preparations available in which actives are bitter in taste. The improved palatability in these products has prompted the development of numerous formulations, which improved performance and acceptability. The bitterness of preparation also leads to patient incompliance. So masking of bitterness becomes essential and done by masking the bitter taste of drugs by either decreasing its oral solubility on ingestion or decreasing the amount of drug particles exposed to taste buds thereby reducing the perception of bitter taste. Methods commonly used for taste masking involves various physical and chemical method that prevent the interaction of taste bud with drugs and are based on coatings, solid dispersion system and ion exchange resin, entrapment method and masking of taste buds etc. Taste masking of bitter drugs become necessity in case of oral administration and selection of technology depends upon the bitterness of drugs and their compatibility with taste masking agents that does not affect the bioavailability of drug

Ilomastat is a matrix metalloproteinase inhibitor (MMPi) that has shown the potential to inhibit scarring (fibrosis) by mediating healing after injury or surgery. A long lasting ocular implantable pharmaceutical formulation of ilomastat is being developed to mediate the healing process to prevent scarring after glaucoma filtration surgery. The ilomastat implant was coated with water permeable and biocompatible phosphoryl choline polymer (PC1059) displayed extended slow release of ilomastat in vitro and in vivo. The ocular distribution of ilomastat from the implant in rabbits at day 30 post surgery was determined by the extraction of ilomastat and its internal standard marimastat from the ocular tissues, plasma, aqueous humour and vitreous fluid followed by capillary-flow liquid chromatography (cap-LC), the column effluent was directed into a triple quadrupole mass spectrometer operating in product scan mode. The lower limits of quantification (LLOQs) were 0.3 pg/μL for ocular fluids and plasma, and 3 pg/mg for ocular tissues. The extraction recoveries were 90-95% for ilomastat and its internal standard from ocular tissues. Ilomastat was found in ocular fluids and tissues at day 30 after surgery. The level of ilomastat was 18 times higher in the aqueous humour than vitreous humour. The concentration ranking of ilomastat in the ocular tissues was sclera > bleb conjunctiva > conjunctiva (rest of the eye) > cornea. Mass spectrometry analysis to confirm the presence of ilomastat in the ocular tissues and fluids at day 30 post-surgery establishes the extended release of ilomastat can be achieved in vivo, which is crucial information for optimisation of the ilomastat coated implant.