Mechanistic insights of the controlled release capacity of polar functional group in transdermal drug delivery system: the relationship of hydrogen bonding strength and controlled release capacity

BackgroundHydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal patch. However, the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported, and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive (PSA) was not well understood. The present study shed light on this relationship.MethodsAcrylate PSAs with amide group were synthesized by a free radical-initiated solution polymerization. Six drugs, i.e., etodolac, ketoprofen, gemfibrozil, zolmitriptan, propranolol and lidocaine, were selected as model drugs. In vitro drug release and skin permeation experiments and in vivo pharmacokinetic experiment were performed. Partial correlation analysis, fourier-transform infrared spectroscopy and molecular simulation were conducted to provide molecular details of drug-PSA interactions. Mechanical test, rheology study, and modulated differential scanning calorimetry study were performed to scrutinize the free volume and molecular mobility of PSAs.ResultsRelease rate of all six drugs from amide PSAs decreased with the increase of amide group concentrations; however, only zolmitriptan and propranolol showed decreased skin permeation rate. It was found that drug release was controlled by amide group through hydrogen bonding, and controlled release extent was positively correlated with hydrogen bonding strength.ConclusionFrom these results, we concluded that drugs with strong hydrogen bond forming ability and high skin permeation were suitable to use amide PSAs to regulate their release rate from patch.     

Coalescence of Extracellular Matrix (ECM) from Porcine Urinary Bladder (UBM) with a Laser-Activated Chitosan-Based Surgical Adhesive

Abstract

Urinary bladder matrix (UBM) has been extensively investigated as a naturally occurring biomaterial in therapeutic applications for tissue repair or regeneration, while other strategies involve biopolymers such as chitosan for tissue reconstruction. The coalescence of UBM with chitosan has considerable potential in enhancing tissue reconstruction. Characterisation of a novel, laser-activated, chitosan-based, thin-film surgical adhesive with UBM in various morphologies showed that the films had increased surface rugosities and crystallinities (R_a approx. 0.83 um, approx. 12% crystallinity) when compared to the chitosan adhesive alone (R _a = 0.74 um, 7% crystallinity). Tensile strength of the films was significantly increased by the addition of UBM in particulate form (12.1–32.4 MPa). Furthermore, tissue adhesion strengths using these hybrid biomaterials were maintained at approx. 15 kPa compared to 3 kPa for fibrin glue. Histological analysis demonstrated that laser irradiation of the UBM-chitosan adhesive biomaterial caused no thermal damage to tissue. Examination of the cellular response at the material interface showed that 3T3 fibroblasts maintained their regular morphology with enhanced growth compared to films of both chitosan and its adhesive form. These results suggest that coalescence of UBM with a chitosan-based adhesive supports the development of biomaterial devices for sutureless wound closure that could enhance tissue repair and reconstruction.     

牙本质半胱氨酸组织蛋白酶研究现状

牙本质基质胶原纤维的降解是导致混合层破坏的重要因素,研究已证实牙本质胶原纤维降解与基质金属蛋白酶(matrix metalloproteinases,MMPs)等内源性蛋白酶密切相关。2010年,首次发现牙本质内存在另一种可降解胶原纤维的半胱氨酸组织蛋白酶(cysteine cathepsins,CCs,CTs),而目前对于半胱氨酸组织蛋白酶的相关研究已成为热点,本文将对牙本质半胱氨酸组织蛋白酶的相关研究进展作一综述。     

Skin and Adhesive Issues With Continuous Glucose Monitors: A Sticky Situation

Background:The purpose of this article is to describe challenges associated with successful use of continuous glucose monitoring (CGM) by young children with type 1 diabetes (T1D) and to detail the techniques and products used to improve the duration of sensor wear.Methods:The DirecNet Study Group conducted 2 studies in 169 children with T1D between the ages of 1 and 9 years who were instructed to wear a CGM device daily. Problems related to skin irritation and sensor adhesiveness in these young children presented challenges to daily use of the CGM. Study coordinators instituted a variety of techniques using commercially available products to attempt to overcome these problems.Results:Three primary factors that contributed to reduced CGM use were identified: the limited body surface area in smaller children, ambient temperature and humidity, as well as the type and duration of physical activity. Using supplemental products to minimize the impact of these factors resulted in improved adherence and reduced skin irritation.Conclusion:Achieving satisfactory adhesion of the CGM sensor and transmitter may involve finding the right supplemental product or combination of products through trial and error. Optimizing adhesion and minimizing skin irritation can significantly improve duration of use and tolerability of CGM devices by young children.     

Ultra-high-speed videography of resin–dentin interface failure dynamics under tensile load

ObjectivesUltra-high-speed (UHS) videography was used to visualize the fracture phenomena at the resin–dentin interface during micro-tensile bond strength (μTBS) test. We also investigated whether UHS videography is applicable for failure-mode analysis.MethodsTen human mid-coronal dentin surfaces were bonded using Clearfil SE Bond either in self-etching (SE) or etch-and-rinse (ER) mode. After 24-h water storage, the samples were cut into beams for μTBS test and tested at a cross-head speed of 1 mm/min. The fracture phenomena at the bonded interface were captured using a complementary metal–oxide–semiconductor digital UHS camera at 299,166 frames per second. The failure modes were classified using UHS videography, followed by scanning electron microscopy (SEM) analysis. The failure-mode distributions determined by UHS videography and SEM analysis were statistically analyzed using Fisher’s exact test with Bonferroni correction.ResultsThe crack-propagation speed exceeded 1,500 km/h. No significant difference was found between the SEM and UHS videography failure-mode distributions in the SE mode. A significant difference appeared between them in the ER mode. Significant differences in the incidence of cohesive failures within the adhesive and at the adhesive–composite interface between the SE and ER modes were identified by both SEM and UHS videography.SignificanceUHS videography enabled visualization of the fracture dynamics at the resin– dentin interfaces under tensile load. However, the resolution at such high frame rate was insufficient to classify the failure mode as precisely as that of SEM. Nevertheless, UHS videography can provide more detailed information about the fracture origin and propagation.