Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery

Limited tissue selectivity and targeting of anticancer therapeutics in systemic administration can produce harmful side effects in the body. Various polymer nano-vehicles have been developed to encapsulate therapeutics and prevent premature drug release. Dually responsive polymeric vesicles (polymersomes) assembled from temperature-/pH-sensitive block copolymers are particularly interesting for the delivery of encapsulated therapeutics to targeted tumors and inflamed tissues. We have previously demonstrated that temperature-responsive poly(N-vinylcaprolactam) (PVCL)-b-poly(dimethylsiloxane) (PDMS)-b-PVCL polymersomes exhibit high loading efficiency of anticancer therapeutics in physiological conditions. However, the in-vivo toxicity of these polymersomes as biocompatible materials has not yet been explored. Nevertheless, developing an advanced therapeutic nanocarrier must provide the knowledge of possible risks from the material’s toxicity to support its future clinical research in humans. Herein, we studied pH-induced degradation of PVCL₁₀-b-PDMS₆₅-b-PVCL₁₀ vesicles in-situ and their dually (pH- and temperature-) responsive release of the anticancer drug, doxorubicin, using NMR, DLS, TEM, and absorbance spectroscopy. The toxic potential of the polymersomes was evaluated in-vivo by intravenous injection (40 mg kg⁻¹ single dose) of PVCL₁₀-PDMS₆₅-PVCL₁₀ vesicles to mice. The sub-acute toxicity study (14 days) included gravimetric, histological, and hematological analyses and provided evidence for good biocompatibility and non-toxicity of the biomaterial. These results show the potential of these vesicles to be used in clinical research.     

Evaluation of the In Vitro Wound-Healing Potential of Ayahuasca

Ayahuasca is an Amazonian drink, which contains β-carboline alkaloids and N,N-dimethyltryptamine. The aim of this study was to evaluate the healing potential of decoctions of a commercial mixture, four individual plants and four mixtures of two plants used in the ayahuasca preparation. Thus, the cytotoxic potential of the samples was evaluated and a wound-healing assay was performed with a NHDF cell line. Subsequently, a parallel artificial membrane permeability assay was also performed, to verify if any psychoactive compound could be absorbed by skin fibroblasts. The integrity and permeability of the cell layer were also evaluated, using the transepithelial electrical resistance assay and Lucifer yellow permeability assay, respectively. The compounds absorbed by the cell layer were quantified by high-performance liquid chromatography coupled to a diode array detector. The results showed that only one sample showed cytotoxicity and all the others promoted the migration of skin fibroblasts. Additionally, it was also verified that β-carbolynic alkaloids and N,N-dimethyltriptamine were not absorbed by the cell layer, and in general, did not interfere with its permeability and integrity. To the best of our knowledge, this is the first study where ayahuasca’s wound-healing potential was evaluated.     

Spectrum of partial automorphisms of regular rooted tree

Semigroup Forum - We study properties of eigenvalues of a matrix associated with a randomly chosen partial automorphism of a regular rooted tree. We show that asymptotically, as the level number...     

Existence and uniqueness of solutions in H1(Δ) of a general class of non-linear functional equations

A functional analytic method is used to prove the existence and the uniqueness of a solution in the Banach space H₁(Δ) of a general class of non-linear functional equations. This general class includes some specific functional equations studied recently. Our results simplify and improve the existing results for these specific equations. Moreover, for one of them, we give an answer to an open problem.     

Asymptotically sharp uniform estimates in a scalar spectral stiff problemEstimations asymptotiques uniformes pour le spectre d'un problème scalaire raide

Estimates of convergence rates for rescaled eigenvalues of the stiff Neumann problem for the Laplacian are obtained. The bounds are expressed in terms of the stiffness ratio and properties of the limit spectrum both for low and middle frequency ranges. To cite this article: M. Lobo et al., C. R. Mecanique 331 (2003).     

A “discretization” technique for the solution of ODEs

A functional-analytic technique was developed in the past for the establishment of unique solutions of ODEs in H₂(D) and H₁(D) and of difference equations in ?₂ and ?₁. This technique is based on two isomorphisms between the involved spaces. In this paper, the two isomorphisms are combined in order to find discrete equivalent counterparts of ODEs, so as to obtain eventually the solution of the ODEs under consideration. As an application, the Duffing equation and the Lorenz system are studied. The results are compared with numerical ones obtained using the 4th order Runge-Kutta method. The advantages of the present method are that, it is accurate, the only errors involved are the round-off errors, it does not depend on the grid used and the obtained solution is proved to be unique.