Inhaled/oral insulin have been investigated as an alternative to injectable insulin, but are met with unsatisfactory outcomes. Transdermal administration bears several advantages unmet by inhalation/oral delivery, but macromolecular drugs permeation is poor. This study explored microwave to elicit transdermal insulin permeation, and compared against conventional permeation enhancers (fatty acids) in vitro/in vivo. The transdermal insulin permeation was promoted by microwave (2450 MHz/1 mW) > oleic acid (monounsaturated) ~ linoleic acid (double unsaturated bonds). The linolenic acid (triple unsaturated bonds) or combination of microwave/fatty acid reduced skin insulin permeation. Transdermal insulin permeation enhancement was attributed to epidermal lipid bilayer fluidization (CH) and corneocyte shrinkage due to keratin condensation (OH/NH, CO), which had aqueous pore enlarged to facilitate insulin transport. Its reduction by linolenic acid, a molecularly larger and rigid fatty acid with higher surface tension, was due to reduced fatty acid permeation into epidermis and minimal skin microstructural changes. The oleic acid, despite favoured skin microstructural changes, did not provide a remarkably high insulin permeation due to it embedded in skin as hydrophobic shield to insulin transport. Microwave penetrates skin volumetrically with no chemical residue retention. It alone promoted insulin absorption and sustained blood glucose level reduction in vivo.
Alginate pellets prepared by the aqueous agglomeration technique experience fast drug dissolution due to the porous pre-formed calcium alginate microstructure.
Transdermal drug delivery is impeded by the natural barrier of epidermis namely stratum corneum. This limits the route to transport of drugs with a log octanol-water partition coefficient of 1 to 3, molecular weight of less than 500 Da and melting point of less than 200°C. Nanotechnology has received widespread investigation as nanocarriers are deemed to be able to fluidize the stratum corneum as a function of size, shape, surface charges, and hydrophilicity-hydrophobicity balance, while delivering drugs across the skin barrier. This review provides an overview and update on the latest designs of liposomes, ethosomes, transfersomes, niosomes, magnetosomes, oilin- water nanoemulsions, water-in-oil nanoemulsions, bicontinuous nanoemulsions, covalently crosslinked polysaccharide nanoparticles, ionically crosslinked polysaccharide nanoparticles, polyelectrolyte coacervated nanoparticles and hydrophobically modified polysaccharide nanoparticles with respect to their ability to fuse or fluidize lipid/protein/tight junction regimes of skin, and effect changes in skin permeability and drug flux. Universal relationships of nanocarrier size, zeta potential and chemical composition on transdermal permeation characteristics of drugs will be developed and discussed.