Mechanistic Investigation of Peptide Sorption and Acylation in Poly(lactic-co-glycolic acid).

The aim of this dissertation is to understand peptide sorption to PLGA, with the goal of stabilizing octreotide against acylation within PLGA. These studies describe the first detailed investigations of peptide sorption to low Mw free-acid PLGA. A new class of inhibitors of the sorption and acylation of a model peptide, octreotide, has been described. Long-term sorption studies indicated that CaCl2 and MnCl2 disrupt peptide sorption to PLGA with the inorganic divalent cation inhibitors translates to inhibition of peptide acylation. The octreotide-PLGA interactions are mostly irreversible in aqueous solution and strongly increase solubility of octreotide in acetonitrile. Only the addition of solvent or 5% SDS resulted in a substantial desorption from PLGA, strongly suggesting the irreversibility is due to hydrophobic interactions or hydrogen-bonding between the peptide and PLGA. The kinetics of peptide sorption to PLGA was studied and well described using a biexponential model. Sorption is reduced at low octreotide concentrations, high ionic strength and low temperature, suggesting polymer mobility plays a critical role in the sorption interaction. Although irreversible, peptide sorption follows Langmuir behavior. Sorption of octreotide decreased as the pH of the solutions tested was decreased toward the pKa of PLGA carboxylates. Reducing the number of total acid end-groups by increasing the PLGA molecular weight also decreased octreotide sorption. These results indicate the critical role of ionized PLGA acid end-groups during the peptide sorption pathway. Quantification of the maximal amount of peptide sorbed at high solution concentration showed this value to be similar to the total number of PLGA acid end-groups for RG502H and RG503H. The low amount of sorption to the higher molecular-weight RG504H is also consistent with peptide partitioning into the polymer phase. Film sectioning after peptide sorption showed a proportional decrease in peptide remaining in the polymer with fraction of film removed. Hence, these results suggest both multilayer adsorption and absorption of peptide to free-acid PLGA.Ph.D.Chemical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/64668/1/asophocl_1.pd

Group Analysis of Variable Coefficient Diffusion-Convection Equations. I. Enhanced Group Classification

We discuss the classical statement of group classification problem and some its extensions in the general case. After that, we carry out the complete extended group classification for a class of (1+1)-dimensional nonlinear diffusion--convection equations with coefficients depending on the space variable. At first, we construct the usual equivalence group and the extended one including transformations which are nonlocal with respect to arbitrary elements. The extended equivalence group has interesting structure since it contains a non-trivial subgroup of non-local gauge equivalence transformations. The complete group classification of the class under consideration is carried out with respect to the extended equivalence group and with respect to the set of all point transformations. Usage of extended equivalence and correct choice of gauges of arbitrary elements play the major role for simple and clear formulation of the final results. The set of admissible transformations of this class is preliminary investigated.Comment: 25 page

Clinical performance of a novel textile interface for neonatal chest electrical impedance tomography

Objective: Critically ill neonates and infants might particularly benefit from continuous chest electrical impedance tomography (EIT) monitoring at the bedside. In this study a textile 32-electrode interface for neonatal EIT examination has been developed and tested to validate its clinical performance. The objectives were to assess ease of use in a clinical setting, stability of contact impedance at the electrode–skin interface and possible adverse effects. Approach: Thirty preterm infants (gestational age: 30.3 ± 3.9 week (mean ± SD), postnatal age: 13.8 ± 28.2 d, body weight at inclusion: 1727 ± 869 g) were included in this multicentre study. The electrode–skin contact impedances were measured continuously for up to 3 d and analysed during the initial 20-min phase after fastening the belt and during a 10 h measurement interval without any clinical interventions. The skin condition was assessed by attending clinicians. Main results: Our findings imply that the textile electrode interface is suitable for long-term neonatal chest EIT imaging. It does not cause any distress for the preterm infants or discomfort. Stable contact impedance of about 300 Ohm was observed immediately after fastening the electrode belt and during the subsequent 20 min period. A slight increase in contact impedance was observed over time. Tidal variation of contact impedance was less than 5 Ohm. Significance: The availability of a textile 32-electrode belt for neonatal EIT imaging with simple, fast, accurate and reproducible placement on the chest strengthens the potential of EIT to be used for regional lung monitoring in critically ill neonates and infants