Biocompatibility and erosion behavior of implants made of triglycerides and blends with cholesterol and phospholipids

Abstract Triglycerides are a promising class of material for the parenteral delivery of drugs and have become the focus of tremendous research efforts in recent years. The aim of this study was to investigate the biocompatibility of glyceroltripalmitate as well as the influence of cholesterol and distearoyl-phosphatidyl-choline (DSPC) on the erosion behavior of the lipid. For these investigations, two in vivo studies were carried out, in which cylindrical matrices of 2 mm diameter were manufactured and subcutaneously implanted in immunocompetent NMRI-mice. After excision of the implants, tissue reactions of the animals as well as changes in the weight, shape and microstructure of the implants were investigated. The triglyceride and cholesterol showed good biocompatibility, as indicated by their minimal encapsulation in connective tissue and the absence of inflammatory reactions. Increasing the levels of phospholipid in the implants, however, led to an increased inflammatory reaction. In contrast to cholesterol, which did not affect erosion, the incorporation of DSPC into the triglyceride matrices led to clearly visible signs of degradation

An Approach to Classify Degradable Polymers

AbstractDespite tremendous progress towards a better understanding of polymer erosion, degradable polymers could so far not be classified according to their erosion behavior. It was the goal of this study to close this gap and to find those parameters that determine how a polymer erodes. Therefore, a dimensionless erosionnumber ε was defined, that can be calculated from the velocity of polymer degradation and water diffusion in the polymer bulk. s indicates whether erosion is a surface phenomenon (surface erosion) or whether it affects the complete polymer bulk bulk erosion). ε is characteristic for a polymer type and depends on the diffusivity of water inside polymer matrix, on the molecular weight of a polymer, and the dimensions of an eroding polymer matrix. The proposed erosion theory shows that ‘surface erosion’ and ‘bulk erosion’ are two potential erosion pathways that are open to any degradable polymer.</jats:p

Towards controlled release of BDNF — Manufacturing strategies for protein-loaded lipid implants and biocompatibility evaluation in the brain

It was the aim of this study to establish triglyceride matrices as potential carriers for long-term release of brain-derived neurotrophic factor (BDNF), a potential therapeutic for Huntington's disease. First, four different manufacturing strategies were investigated with lysozyme as a model substance: either lyophilized protein was mixed with lipid powder, or suspended in organic solution thereof (s/o). Or else, an aqueous protein solution was dispersed by w/o emulsion in organic lipid solution. Alternatively, a PEG co-lyophilization was performed prior to dispersing solid protein microparticles in organic lipid solution. After removal of the solvent(s), the resulting powder formulations were compressed at 250 N to form mini-cylinders of 2 mm diameter, 2.2 mm height and 7 mg weight. Protein integrity after formulation and release was evaluated from an enzyme activity assay and SDS-PAGE. Confocal microscopy revealed that the resulting distribution of FITC-lysozyme within the matrices depended strongly on the manufacturing method, which had an important impact on matrix performance: matrices with a very fine and homogeneous protein distribution (PEG co-lyophilization) continually released protein for 2 months. The other methods did not guarantee a homogeneous distribution and either failed in sustaining release for more than I week (powder mixture), completely liberating the loading (s/o dispersion) or preserving protein activity during manufacturing (w/o emulsion, formation of aggregates and 25% activity loss). Based on these results, miniature-sized implants of I mm diameter, 0.8 mm height and I mg weight were successfully loaded by the PEG co-lyophilization method with 2% BDNF and 2% PEG. Release studies in phosphate buffer PH 7.4 at 4 and 37 degrees C revealed a controlled release of either 20 or 60% intact protein over one month as determined by ELISA. SDS-PAGE detected only minor aggregates in the matrix during release at higher temperature. In vivo evaluation of lipid cylinders in the striatum of rat brains revealed a biocompatibility comparable to silicone reference cylinders. (C) 2007 Elsevier B.V. All rights reserved

How Stealthy are PEG-PLA Nanoparticles? An NIR In Vivo Study Combined with Detailed Size Measurements

Detailed in vivo and ex vivo analysis of nanoparticle distribution, accumulation and elimination processes were combined with comprehensive particle size characterizations