Effect of ion pair strategy on transdermal delivery of guanfacine: Which factor dominates drug permeation?

Ion pair is an effective chemical approach to promoting drug transdermal permeation, and the traditional interpretation for its enhanced permeation effect is mainly attributed to counterions altering the physicochemical properties of the drug (lipophilicity, melting point, etc.). In this work, guanfacine (GFC), a non-stimulant for anti-attention deficit and hyperactivity disorder (ADHD), was used as a model drug, and several organic or inorganic acids were designed thereby successfully constructing ion pairs. The transdermal permeation ability of ion pairs through isolated porcine skin was observed and ranked as follows: guanfacine caprylate (GFC-CA) > GFC > guanfacine laurate (GFC-LA) > guanfacine fumarate (GFC-FA) > guanfacine hydrochloride (GFC-HA) > guanfacine palmitate (GFC-PA). The effect of key physicochemical properties (octanol-water partition coefficient, molecular volume, melting point) on the transdermal permeation rate of the model drug was analyzed in detail. In addition, GFC-CA was observed to alter the lipid structure of the skin, suggesting the traditional explanation of the action of ion pair may be inadequate and underrated, and ion pair may also enhance permeation by disrupting skin structure. The intriguing phenomenon is expected to provide a novel approach to achieving precise transdermal drug delivery.

A mixed-method approach to determining contact matrices in the Cox's Bazar refugee settlement.

Contact matrices are an important ingredient in age-structured epidemic models to inform the simulated spread of the disease between subgroups of the population. These matrices are generally derived using resource-intensive diary-based surveys and few exist in the Global South or tailored to vulnerable populations. In particular, no contact matrices exist for refugee settlements-locations under-served by epidemic models in general. In this paper, we present a novel, mixed-method approach for deriving contact matrices in populations, which combines a lightweight, rapidly deployable survey with an agent-based model of the population informed by census and behavioural data. We use this method to derive the first set of contact matrices for the Cox's Bazar refugee settlement in Bangladesh. To validate our approach, we apply it to the UK population and compare our derived matrices with well-known contact matrices collected using traditional methods. Our findings demonstrate that our mixed-method approach successfully addresses some of the challenges faced by traditional and agent-based approaches to deriving contact matrices. It also shows potential for implementation in resource-constrained environments. This work therefore contributes to a broader aim of developing new methods and mechanisms of data collection for modelling disease spread in refugee and internally displaced person (IDP) settlements and better serving these vulnerable communities.

A high efficiency and high power L-band relativistic magnetron with all-cavity extraction.

Relativistic magnetron (RM) is a promising high-power microwave source, whose advantages include high efficiency, high power, and compact configuration. Enhancing power efficiency and output power are the most important two development directions for RM. Based on the two targets, a high efficiency and high power RM is presented and investigated numerically and experimentally in this paper. When the diode voltage is 485 kV, the beam current is 6.9 kA, and the magnetic field is 0.34 T, and high power microwave is generated with the power of 1.35 GW, frequency of 1.47 GHz, and power efficiency of 40.3% in the experiments.

Theoretical investigations on radiation generation of TEM, linearly or circularly polarized TEn1 coaxial waveguide mode in relativistic magnetron.

The physical mechanism of the radiation generation of all possible output modes of the relativistic magnetron (RM) with all cavity-magnetron axial extraction technique is theoretically analysed, and the necessary conditions for generating these modes are obtained respectively. Assuming that n 0 is the number of the electron spokes, N ≥ 4 as the total number of the cavities is an even number, and k is a nonnegative integer, some conclusions can be drawn as follows. If n 0 = kN is true, no mode can be excited in the coaxial waveguide; if n 0 = (2k + 1)N/4 is true, the linearly polarized modes can be excited in the coaxial waveguide; if n 0 = (4k + 2)N/4 is true, the TEM mode and the linearly polarized modes can be excited in the coaxial waveguide; if n 0 takes other value, the left and right circularly polarized modes can be excited in the coaxial waveguide and the directions of rotation of the circularly polarized modes can be reversed with the reversion of the direction of rotation of the electron spokes; in addition, some other regular characteristics of the corresponding mode excitation are presented in detail in this paper. Such unique attractive properties that have been verified by the cold and hot simulations in this paper make it possible for this type of RM to meet application requirements of various high power microwave (HPM) modes.