Gary W. Cleary

Microneedles for Drug Delivery

The theme section highlighted in this issue of Pharmaceutical Research provides a snapshot of the latest information on today’s microneedle research and development, predominately in transdermal applications. Fifteen original papers from academia and industry cover research and development of microneedles from concept to human clinical studies and everything in between. The research presented here is diverse in the use of various materials used to make microneedles and in the molecules that can be delivered, from small molecules that generally cannot permeate intact skin enough to reach therapeutic blood levels, to large molecules, including vaccines, proteins, and polypeptides. These studies also show a fundamentally different approach to today’s injection methodology of syringes and needles. Drug molecules inserted into the skin via microneedles cause no pain and no bleeding and allow for delivering drugs from dry dissolvable microneedles rather than liquids. After use and during disposal of microneedles, particularly the dissolvable ones, there are no accidental needle sticks and fewer issues with biohazardous waste.

A new class of pressure-sensitive adhesives based on interpolymer and polymer-oligomer complexes

On the basis of previous concepts concerning the molecular nature of pressure-sensitive adhesion, a simple method of preparing new adhesives with the desired mechanical and adhesive behavior and water-absorbability via mixing of nonadhesive polymers has been developed. Pressure-sensitive adhesion is related to the combination of a high energy of cohesion and a large free volume, which leads to a high molecular mobility. This method is based on the formation of interpolymer or polymer-oligomer complexes during mixing of macromolecules capable of hydrogen, electrostatic, or ionic bonding. In interpolymer complexes, a high cohesion results from the formation of bonds between macromolecules carrying complementary groups in main chains, whereas free volume is related to defectiveness of the resulting network and formation of loops. In complexes formed by a high-molecular-mass polymer and an oligomer carrying complementary reactive groups at ends of short chains, a high energy of cohesion is related to their interaction with mainchain functional groups of the polymer, whereas a relatively large free volume is associated with the length and flexibility of intermacromolecular crosslinks via oligomer chains. The adhesive and viscoelastic properties of adhesives and their water absorbability are regulated by changes in the composition of mixtures of a film-forming polymer with a polymer or oligomer crosslinker and a plasticizer. In this case, an increase in cohesive strength is achieved owing to an increase in the crosslinker concentration, while the enhancement of free volume is ensured by the increasing plasticizer content in the blend. Adhesive materials capable of adherence to wet substrates, hydroactivated adhesives, and adhesion moisture sorbents have been prepared for the first time.

Tensile properties and adhesion of water-absorbing hydrogels based on ternary poly(N-vinyl pyrrolidone)/poly(ethylene glycol)/poly(methacrylic acid-co-ethylacrylate) blends

Rubber-like elasticity and pressure-sensitive adhesion of ternary blends of high-molecularweight poly(N-vinyl pyrrolidone) (PVP) with oligomeric poly(ethylene glycol) (PEG) of molecular weight 400 g/mol and a co-polymer of methacrylic acid with ethylacrylate (PMAA-co-EA) is due to formation of a interpolymer hydrogen bonded complex. In the ternary blend, PVP is present in a greater amount and acts as a film-forming polymer (FFP). As each short chain of PEG bears two terminal hydroxyl groups, which are capable of forming hydrogen bonds with the carbonyl groups in PVP repeat units, PEG behaves as a reversible carcass-like cross-linker (CLC) between long PVP macromolecules. In addition, the PMAA-co-EA forms a ladder-like interpolymer complex with PVP via hydrogen bonding of carboxyl groups and serves as a ladder-like cross-linker (LLC) of PVP. Adhesion behavior, mechanical properties and water-absorbing capacity of PVP/PEG/PMAA-co-EA blends are functions of blend composition. The CLC (PEG) endows pressure-sensitive adhesion to PVP blends, acting simultaneously as PVP plasticizer, as well as enhancer of cohesive strength. While the PVP/PEG inter-polymer complex is soluble in water, the LLC (PMAA-co-EA) provides insolubility and swellability, increasing further the cohesive strength of the blend composition. At high LLC concentrations, the blends lose their initial tack but become tacky upon water uptake. In this way, ternary PVP/PEG/PMAA-co-EA blends combine tack, typical of conventional hydrophobic pressure-sensitive adhesives, with the capability to adhere to highly hydrated substrates, typical of bioadhesives.