Drug crystallization on and in the skin has been reported following application of topical or transdermal formulations. This study explored novel probe-based approaches including localized nanothermal analysis (nano-TA) and photothermal microspectroscopy (PTMS) to investigate and locate drug crystals in the stratum corneum (SC) of porcine skin following application of simple ibuprofen (IBU) formulations. We also conducted in vitro skin permeation studies and tape stripping. The detection of drug crystals in the SC on tape strips was confirmed using localized nano-TA, based on the melting temperature of IBU. The melting of IBU was also evident as indicated by a double transition and confirmed the presence of drug crystals in the SC. The single point scans of PTMS on the tape strips allowed collection of the photothermal FTIR spectra of IBU, confirming the existence of drug crystals in the skin. The combined methods also indicated that drug crystallized in the SC at a depth of ∼4-7 μm. Future studies will examine the potential of these techniques to probe crystallization of other commonly used actives in topical and transdermal formulations.
Type 1 diabetes mellitus is associated with a high risk for bone fractures. Although bone mass is reduced, bone quality is also dramatically altered in this disorder. However, recent evidences suggest a beneficial effect of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) pathways on bone quality. The aims of the present study were to conduct a comprehensive investigation of bone strength at the organ and tissue level; and to ascertain whether enzyme resistant GIP or GLP-1 mimetic could be beneficial in preventing bone fragility in type 1 diabetes mellitus. Streptozotocin-treated mice were used as a model of type 1 diabetes mellitus. Control and streptozotocin-diabetic animals were treated for 21 days with an enzymatic-resistant GIP peptide ([D-Ala(2) ]GIP) or with liraglutide (each at 25 nmol/kg bw, ip). Bone quality was assessed at the organ and tissue level by microCT, qXRI, 3-point bending, qBEI, nanoindentation, and Fourier-transform infrared microspectroscopy. [D-Ala2]GIP and liraglutide treatment did prevent loss of whole bone strength and cortical microstructure in the STZ-injected mice. However, tissue material properties were significantly improved in STZ-injected animals following treatment with [D-Ala2]GIP or liraglutide. Treatment of STZ-diabetic mice with [D-Ala(2) ]GIP or liraglutide was capable of significantly preventing deterioration of the quality of the bone matrix. Further studies are required to further elucidate the molecular mechanisms involved and to validate whether these findings can be translated to human patients.