Drug delivery into the skin by degradable particles

Recently, it was demonstrated that particles could be utilized as carrier systems for drugs into the hair follicles. In the present study, a two-component drug delivery system is presented consisting of degradable particles loaded with fluorescein isothiocyanate and a separate protease formulation for degradation. The particles were applied alone, 30 min previous to the protease application and simultaneously with the protease onto porcine skin. Subsequently, biopsies were removed, and the penetration depths of the particles were analyzed using laser scanning microscopy.The obtained results demonstrate that the particles alone achieved a penetration depth of around 900 μm. Similar results were obtained for the successive application of particles and protease, whereas a release of the fluorescent dye was only observed in the upper 250 μm corresponding to the penetration depth of the protease. In the case of the simultaneous application, the particles were partly dissolved before application, leading to a reduced particle size and diminished penetration depth.The results revealed that degradable particles are a promising tool for drug delivery into the skin.     

Hematopoietic stem cell transplantation recovers insulin deficiency in type 1 diabetes mellitus associated with IPEX syndrome

Immune dysregulation, polyendocrinopathy, enteropathy, and X‐linked (IPEX) syndrome is an autoimmune disorder caused by the dysfunction of FOXP3, which leads to regulatory T‐(Treg) cell dysfunction and subsequently autoimmunity including type 1 diabetes mellitus (T1D). Presently, allogeneic hematopoietic stem cell transplantation (HSCT) is a potential curative therapy for IPEX syndrome, but not for T1D. Generally, after complete loss of pancreatic β‐cells, HSCT cannot improve the prognosis of T1D. Here, we report the case of a 16‐year‐old adolescent with late‐onset of FOXP3 R347H mutation associated IPEX syndrome with T1D, where insulin dependency was ameliorated following HSCT. This patient with insulin‐dependent diabetes mellitus required insulin dosage of 1.28 U/kg/day for 1 month before HSCT. Although the results of glucose homeostasis before HSCT revealed impaired insulin secretion and low ΔC‐peptide immunoreactivity (CPR, 1.0 ng/mL), the patient withdrew insulin infusion and remained euglycemic at 15 months after HSCT, and had normal β‐cell function with improved ΔCPR (3.4 ng/mL) at 20 months after HSCT. The present case suggests that HSCT for T1D‐associated IPEX syndrome improves Treg deficiency and prevents elimination of β‐cells. We speculate that the period from the onset of T1D to HSCT could affect the therapeutic efficacy for T1D with IPEX, and early intervention with HSCT before or immediately after the onset of DM can rescue β‐cells and remit T1D completely. Our study elaborates not only the therapeutic strategy for T1D with IPEX, but also the pathogenic mechanism in general T1D.     

3D Printing of Tough Gels Having Tunable Elastic Modulus from the Same Pre‐Gel Solution

A gel forming method with sections with different elastic modulus is developed. Gels with hardness distribution are formed from one base gel material by adjusting the crosslinking density of the polymer network using a 3D gel printer. It is confirmed that hardness is arranged as designed by using mixing rules of composite materials. Furthermore, as a prototype of a practical gel application, a gel finger model having a soft‐fleshy part and a hard‐bony part is printed. 3D printing of an organ model that reproduces a realistic feel that takes not only the shape of the organ but also the distribution of hardness into consideration may become possible.