Controlled-release of opioids for improved pain management

The adequate treatment of pain remains one of the major medical challenges. Morphine and other opioid drugs are most commonly used to counteract moderate to severe pain, but they are also increasingly accessed by patients with chronic non-malignant pain. To achieve long-term analgesia, opioid therapy still represents the standard treatment for chronic pain alleviation. This work presents an overview of current strategies aiming at controlled opioid release. Two important, and intrinsically linked, features are discussed in detail: the used formulations (i.e. polymer systems) and the applied drug administration routes. The different administration routes and their associated advantages and limitations are described. Links between the chemical structure of commonly used opioids and suited administration modes and formulations are made. This review can potentially give insight into new opportunities for adequate relief of chronic pain, a societal burden, by means of alternative (non)opioid analgesics and may serve as inspiration for future developments in this area

Statistical mechanics of thin spherical shells

We explore how thermal fluctuations affect the mechanics of thin amorphous spherical shells. In flat membranes with a shear modulus, thermal fluctuations increase the bending rigidity and reduce the in-plane elastic moduli in a scale-dependent fashion. This is still true for spherical shells. However, the additional coupling between the shell curvature, the local in-plane stretching modes and the local out-of-plane undulations, leads to novel phenomena. In spherical shells thermal fluctuations produce a radius-dependent negative effective surface tension, equivalent to applying an inward external pressure. By adapting renormalization group calculations to allow for a spherical background curvature, we show that while small spherical shells are stable, sufficiently large shells are crushed by this thermally generated "pressure". Such shells can be stabilized by an outward osmotic pressure, but the effective shell size grows non-linearly with increasing outward pressure, with the same universal power law exponent that characterizes the response of fluctuating flat membranes to a uniform tension.Comment: 16 pages, 6 figure

Semipermeable elastic microcapsules for gas capture and sensing

Monodispersed microcapsules for gas capture and sensing were developed consisting of elastic semipermeable polymer shells of tuneable size and thickness and pH-sensitive, gas selective liquid cores. The microcapsules were produced using glass capillary microfluidics and continuous on-the-fly photopolymerisation. The inner fluid was 5-30 wt% K2CO3 solution with m-cresol purple, the middle fluid was a UV-curable liquid silicon rubber containing 0-2 wt% Dow Corning® 749 fluid, and the outer fluid was aqueous solution containing 60-70 wt% glycerol and 0.5-2 wt% stabiliser (polyvinyl alcohol, Tween 20 or Pluronic® F-127). An analytical model was developed and validated for prediction of the morphology of the capsules under osmotic stress based on the shell properties and the osmolarity of the storage and core solutions. The minimum energy density and UV light irradiance needed to achieve complete shell polymerisation were 2 J∙cm-2 and 13.8 mW·cm-2, respectively. After UV exposure, the curing time for capsules containing 0.5 wt% Dow Corning® 749 fluid in the middle phase was 30-40 min. The CO2 capture capacity of 30 wt% K2CO3 capsules was 1.6-2 mmol/g depending on the capsule size and shell thickness. A cavitation bubble was observed in the core when the internal water was abruptly removed by capillary suction, whereas a gradual evaporation of internal water led to buckling of the shell. The shell was characterised using TGA, DSC, and FTIR. The shell degradation temperature was 450-460°C