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The release profile of chlorhexidine from the PerioChip (Chip), a biodegradable local delivery system that contains 2.5 mg of chlorhexidine gluconate (CHX) in a cross-linked hydrolyzed gelatin matrix, into the gingival crevice, was evaluated in an in vivo, open label, single-center, 10-day pharmacokinetic study conducted on 19 volunteers with chronic adult periodontitis. Each volunteer had a single chip inserted into each of 4 selected pockets, with probing pocket depths of between 5-8 mm, at time 0. Gingival crevicular fluid (GCF) samples were collected using filter paper strips prior to Chip placement and at 2 h, 4 h, 24 h and 2, 3, 4, 5, 6, 8, and 9 days post-Chip placement. The GCF volume was measured using a calibrated Periotron 6000. Blood samples were collected at times 0, 1, 4, 8, 12 h and 5 days post-dosing. Urine was collected as a total 24-h specimen immediately post-dosing and 2 single samples at time 0, prior to dosing, and 5 days. The CHX was eluted from the paper strips and the CHX levels in GCF, blood and urine quantified using HPLC. The results indicate an initial peak concentration of CHX in the GCF at 2 h post-Chip insertion (2007 microg/ml) with slightly lower concentrations of between 1300-1900 microg/ml being maintained over the next 96 h. The CHX concentration then progressively decreased until study conclusion with significant CHX concentrations (mean=57 microg/ml) still being detectable at study termination. CHX was not detectable in any of the plasma or urine samples at any time point during the study. These results indicate that the PerioChip can maintain clinically effective levels of CHX in the GCF of periodontal pockets for over 1 week with no detectable systemic absorption.

Human plasma has been shown to contain an apolipoprotein that mediates the transport of cholesteryl ester from high density lipoprotein (HDL) to very low density lipoprotein (VLDL) or low density lipoprotein (LDL) This activity, confined to the density >1.063 g/ml interval, has been isolated from HDL and appears as a single migrating species by anionic or sodium dodecyl sulfate/polyacrylamide gel electrophoresis.It is unreactive to antibodies to the major HDL apolipoproteins. Antibodies prepared against this factor and immobilized on Sepharose remove the capacity of HDL and density > 1.21 g/ml fractions as well as whole plasma to transport cholesteryl ester from HDL. The system shows saturation kinetics with respect to plasma LDL and VLDL concentrations, and transport of cholesteryl ester was associated with reciprocal and equimolar back-transport of triglyceride from VLDL and LDL to the HDL fraction. The possible relationship of this apoprotein to apoprotein D is discussed.In human plasma, cholesterol esterification occurs predominately via the lecithin:cholesterol acyltransferase (LCATase; EC 2.3.1.43) reaction. Indeed an acyl-CoA:cholesterol 0-acyltransferase could not be detected in human liver (1), and familial LCATase deficiency is associated with the almost complete absence of cholesteryl ester from plasma liporoteins (2). After incubation of lipoproteins from LCAT-deficient subjects with this enzyme, all lipoprotein fractions were found to contain significant levels of cholesteryl ester, even though low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were not significant substrates for the enzyme (3). It therefore has seemed likely that cholesteryl ester, formed by the LCATase reaction from high density lipoprotein (HDL) substrates, is transferred to nonsubstrate lipoproteins by a transport factor whose nature has not been ascertained. It was earlier shown that, when human plasma was incubated at 370, there was an increase in VLDL cholesteryl ester that was associated with an increased triglyceride content in HDL (4, 5). A cholesteryl ester exchange protein has been identified in the plasma of cholesterol-fed rabbits and is in the density > 1.21 g/ml density fraction (6) although net transport of cholesteryl ester in this case was not shown. Finally, increased cholesteryl ester synthesis by LCATase in human plasma has been shown during alimentary lipemia (7), possibly due to the release of a cholesteryl ester-mediated inhibition of LCATase activity (8).The identity of such a cholesteryl ester transport protein is of considerable potential interest because of its central role in lipoprotein lipid homeostasis. The present research describes the isolation and partial characterization of such a transport protein from human serum. METHODSPreparation of Plasma Lipoproteins. Plasma was taken from blood withdrawn into 0.38% (wt/vol) citrate from healthy volunteers. The major lipoprotein classes (VLDL, p < 1.006 g/ml; LDL, 1.019 < p < 1.063 g/ml; HDL, 1.063 < p < 1.21 g/ml) were prepar...

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