Evaluation of Electrospun PCL-PLGA for Sustained Delivery of Kartogenin

In this study, kartogenin was incorporated into an electrospun blend of polycaprolactone and poly(lactic-co-glycolic acid) (1:1) to determine the feasibility of this system for sustained drug delivery. Kartogenin is a small-molecule drug that could enhance the outcome of microfracture, a cartilage restoration procedure, by selectively stimulating chondrogenic differentiation of endogenous bone marrow mesenchymal stem cells. Experimental results showed that kartogenin did not affect the electrospinnability of the polymer blend, and it had negligible effects on fiber morphology and scaffold mechanical properties. The loading efficiency of kartogenin into electrospun membranes was nearly 100%, and no evidence of chemical reaction between kartogenin and the polymers was detected by Fourier transform infrared spectroscopy. Analysis of the released drug using high-performance liquid chromatography–photodiode array detection indicated an abundance of kartogenin and only a small amount of its major hydrolysis product. Kartogenin displayed a typical biphasic release profile, with approximately 30% being released within 24 h followed by a much slower, constant rate of release up to 28 days. Although additional development is needed to tune the release kinetics and address issues common to electrospun scaffolds (e.g., high fiber density), the results of this study demonstrated that a scaffold electrospun from biodegradable synthetic polymers is a suitable kartogenin delivery vehicle.     

Observation of the internal network structure of a polymer-stabilized liquid crystal via transmission electron microscopy

The internal structure of the network component of a polymer-stabilized liquid crystal has been observed for the first time. These are systems in which a small amount of a monomer is dissolved within a LC host and then polymerized in situ to produce a network. Studies performed on a system prepared using the diacrylate monomer RM60 and the nematic mixture BL087 are presented. The concentration of the monomer was 1 wt %. After formation of the network through photopolymerization of the monomer between Melinex layers within a glass cell, the LC host was removed by dissolving it in heptane. Subsequent observation of the internal network structure by transmission electron microscopy was made possible by bromine staining of the network, followed by embedding and ultramicrotomy. A collection of solid, near-circular objects was observed, of mean diameter 0.13 μm. These objects were found to be highly permeable to bromine vapour, suggesting an open, but homogeneous structure.     

Markov processes conditioned on their location at large exponential times

Suppose that ${\left(X_t\right)}_{t\ge 0}$ is a one-dimensional Brownian motion with negative drift $?\mu$. It is possible to make sense of conditioning this process to be in the state 0 at an independent exponential random time and if we kill the conditioned process at the exponential time the resulting process is Markov. If we let the rate parameter of the random time go to 0, then the limit of the killed Markov process evolves like $X$ conditioned to hit 0, after which time it behaves as $X$ killed at the last time $X$ visits 0. Equivalently, the limit process has the dynamics of the killed “bang–bang” Brownian motion that evolves like Brownian motion with positive drift $+\mu$ when it is negative, like Brownian motion with negative drift $?\mu$ when it is positive, and is killed according to the local time spent at 0.An extension of this result holds in great generality for a Borel right process conditioned to be in some state $a$ at an exponential random time, at which time it is killed. Our proofs involve understanding the Campbell measures associated with local times, the use of excursion theory, and the development of a suitable analogue of the “bang–bang” construction for a general Markov process.As examples, we consider the special case when the transient Borel right process is a one-dimensional diffusion. Characterizing the limiting conditioned and killed process via its infinitesimal generator leads to an investigation of the $h$-transforms of transient one-dimensional diffusion processes that goes beyond what is known and is of independent interest.