Nanomechanical properties of multi-block copolymer microspheres for drug delivery applications.

Biodegradable polymeric microspheres are interesting drug delivery vehicles for site-specific sustained release of drugs used in treatment of osteoarthritis. We study the nano-mechanical properties of microspheres composed of hydrophilic multi-block copolymers, because the release profile of the microspheres may be dependent on the mechanical interactions between the host tissues and the microspheres that aim to incorporate between the cartilage surfaces. Three different sizes of monodisperse microspheres, namely 5, 15, and 30µm, were tested in both dry and hydrated (swollen) states. Atomic force microscopy was used for measuring nanoindentation-based force-displacement curves that were later used for calculating the Young׳s moduli using the Hertz׳s contact theory. For every microsphere size and condition, the measurements were repeated 400-500 times at different surface locations and the histograms of the Young׳s modulus were plotted. The mean Young׳s modulus of 5, 15, and 30µm microspheres were respectively 56.1±71.1 (mean±SD), 94.6±103.4, and 57.6±58.6MPa under dry conditions and 226.4±54.2, 334.5±128.7, and 342.5±136.8kPa in the swollen state. The histograms were not represented well by the average Young׳s modulus and showed three distinct peaks in the dry state and one distinct peak in the swollen state. The peaks under dry conditions are associated with the different parts of the co-polymeric material at the nano-scale. The measured mechanical properties of swollen microspheres are within the range of the nano-scale properties of cartilage, which could favor integration of the microspheres with the host tissue.

Response to exercise in patients after total surgical correction of Tetralogy of Fallot.

Heart rate, blood pressure, physical working capacity, and electrocardiographic changes were evaluated during upright bicycle exercise in 43 asymptomatic patients, aged seven to 41 years, one to 14 years after total surgical correction of tetralogy of Fallot (TF). One hundred and nine normal subjects between the ages of five and 42 years served as controls. The patient and control groups, subdivided by sex and body surface area (BSA), were similar in height and weight. When comparing males to males and females to females with BSA greater than or equal to 1.2 m2, maximal heart rates and working capacities were lower in the patient groups than in the control groups. An inverse relationship was observed between maximal working capacity and age at surgery in both male and female patient groups. By contrast, especially in the males with BSA less than 1.2 m2, the mean maximal heart rates and working capacities did not differ significantly between the patient and control groups. Premature atrial or ventricular contractions were recorded in ten of 43 patients (23%) after exercise. Five of these ten patients had multifocal premature ventricular contractions (PVC) and four had unifocal PVC. In the five patients with multifocal PVC, a short burst of ventricular tachycardia occurred in two, coupling in one, and bigeminal rhythm in two. Cardiac arrhythmia was not observed in the control group. Although our current surgical results are excellent, this study suggests that impaired cardiovascular function persists after corrective surgery and that early surgical treatment may be more desirable. Furthermore, additional data suggest that the exercise procedure may be useful in detecting and managing patients who may develop life-threatening arrhythmias following intraventricular surgery.