Lothar Kleiner

Microstructure of poly(vinyl alcohol) hydrogels produced by freeze/thaw cycling

To understand the reversible gelation and subsequent aging of hydrogels prepared by freeze/thaw processing of poly(vinyl alcohol) (PVOH) solutions, the microstructures of gels prepared by different freeze/thaw protocols and aged to varying extents are studied by cryogenic transmission electron microscopy, solid-state nuclear magnetic resonance, X-ray scattering, and differential scanning calorimetry (DSC). As discussed in the literature, gelation by the freeze/thaw process occurs as a homogeneous aqueous poly(vinyl alcohol) solution is cycled, perhaps multiple times, between temperatures above 0 °C and well below 0 °C. The current investigation has determined that a few percent of chain segments crystallize during the first cycle, organizing themselves into 3-8 nm primary crystallite junctions separated on an irregular mesh by an average spacing of ∼ 30 nm. Aging or imposition of additional freeze/thaw cycles augments the level of crystallinity and transforms the as-formed liquid-like microstructure, characterized in the electron microscope by rounded ∼ 30 nm pores, into a fibrillar network. Observation that the transformation occurs at fixed mesh spacing and approximately constant average crystallite size suggests the formation of secondary crystallites that do not affect network connectivity. Dendritic ice crystallization and possibly spinodal decomposition superimpose on this nanoscale structure a matrix of much larger pores.

Evolution of implantable and insertable drug delivery systems.

The paper describes the development of implantable and insertable drug delivery systems (IDDS) from their early stage in the 1960s until the current stage in the 2010s. It gives a detailed summary of non-degradable and biodegradable systems and their applications in different areas such as vascular disease treatment, birth control, cancer treatment, and eye disease treatment. It also describes the development of various implantable pump systems and some other atypical IDDS, the challenges and the future of IDDS.

Structure formation in injectable poly(lactide–co-glycolide) depots

Solutions of low-molecular-weight poly(lactide-co-glycolide) (PLGA) in organic solvents have been investigated as novel injectable drug depots for drug delivery over periods of weeks to months. In this paper, we investigated the structure formation in a PLGA/benzyl benzoate system, using controlled stress rheometry, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). GPC analysis demonstrated a decrease in molecular weight as a function of time and temperature, indicating degradation. Rheological experiments showed that the flow properties of PLGA/benzyl benzoate solutions were affected by a combination of degradation and gelation; the latter was also detected by an endotherm in DSC and by three-dimensional structure formation studies by rheology. Extent of degradation and gelation of PLGA were shown to depend on the solvent.