Stability and variability of knee kinematics during gait in knee osteoarthritis before and after replacement surgery.

BACKGROUND: Patients with knee osteoarthritis often feel unstable, suffering from buckling (giving way) or even falling. This study aimed at characterising such instability, and following it over time. METHODS: We investigated treadmill walking in knee osteoarthritis, focusing on angular velocity of sagittal plane knee movements. Knee osteoarthritis patients were followed 1 year after replacement surgery, and were compared to healthy peers. Subjects walked at increasing speeds, and maximum speed was registered. To quantify stability, we calculated short-term (lambda(S)) and long-term (lambda(L)) Lyapunov exponents (the exponential rate of divergence, in state space, of trajectories originating from nearest neighbours), as well as the variability of knee movements, the latter just after heel contact. At each measurement session, patients reported how often they had fallen in the preceding period. FINDINGS: Patients had lower maximum walking speed than controls, and walked with reduced variability, post-operatively even more so. Variability was positively related to number of falls. Pre-operatively, patients had higher lambda(S) at the unaffected side, which post-operatively normalized. INTERPRETATION: Slow walking may serve being more cautions. Reducing variability of sagittal knee kinematics appears to reduce fall risk, perhaps involving paying more attention and/or using cocontraction. The pre-operatively higher unaffected side lambda(S) could result from attempts to reduce the kinematic demands on the affected leg, "letting go" the unaffected leg. One year after the operation, this problem with unaffected lambda(S) had disappeared, suggesting recovery. Further study should include short-term and long-term stability, as well as a quantitative measure of perceived instability.

Comparative study of doxorubicin-loaded poly(lactide-co-glycolide) nanoparticles prepared by single and double emulsion methods.

This study describes how the control of doxorubicin (DOX) polarity allows to encapsulate it inside poly(lactide-co-glycolide) (PLGA) nanoparticles formulated either by a single oil-in-water (O/W) or a double water-in-oil-in-water (W/O/W) emulsification method (SE and DE, respectively). DOX is commercially available as a water soluble hydrochloride salt, which is useful for DE. The main difficulty related to DE approach is that the low affinity of hydrophilic drugs to the polymer limits entrapment efficiency. Compared to DE method, SE protocol is easier and should provide an additional gain in entrapment efficiency. To be encapsulated by SE technique, DOX should be used in a more lipophilic molecular form. We evaluated the lipophilicity of DOX in terms of apparent partition coefficient (P) and modulated it by adjusting the pH of the aqueous phase. The highest P values were obtained at pH ranging from 8.6 to 9, i. e. between two DOX pK(a) values (8.2 and 9.6). The conditions favorable for the drug lipophilicity were then used to formulate DOX-loaded PLGA nanoparticles by SE method. DOX encapsulation efficiency as well as release profiles were evaluated for these nanoparticles and compared to those with nanoparticles formulated by DE. Our results indicate that the encapsulation of DOX in nanoparticles formulated by SE provides an increased drug entrapment efficiency and decreases the burst effect.