A personalized FEM model for reproducible measurement of anti-inflammatory drugs in transdermal administration to knee

A personalized model of the human knee for enhancing the inter-individual reproducibility of a measurement method for monitoring Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) after transdermal delivery is proposed. The model is based on the solution of Maxwell Equations in the electric-quasi-stationary limit via Finite Element Analysis. The dimensions of the custom geometry are estimated on the basis of knee circumference at the patella, body mass index, and sex of each individual. An optimization algorithm allows to find out the electrical parameters of each subject by experimental impedance spectroscopy data. Muscular tissues were characterized anisotropically, by extracting Cole–Cole equation parameters from experimental data acquired with twofold excitation, both transversal and parallel to tissue fibers. A sensitivity and optimization analysis aiming at reducing computational burden in model customization achieved a worst-case reconstruction error lower than 5%. The personalized knee model and the optimization algorithm were validated in vivo by an experimental campaign on thirty volunteers, 67% healthy and 33% affected by knee osteoarthritis (Kellgren–Lawrence grade ranging in [1,4]), with an average error of 3%.

Transdermal Delivery of Poly-Hyaluronic Acid-Based Spherical Nucleic Acids for Chemogene Therapy

Spherical nucleic acid (SNA), as a good gene delivery system, has a good application prospect for transdermal administration in skin disorders treatment. However, most of traditional SNA core materials are...

The effect of medicinal electroapplication of the biologically active agent "Pelamine" from the ELAV-8 device on microcirculation in the rabbit ear

The study was the first to study the effect of pulsed electric currents from the ELAV–8 device and the biologically active substance "Pelamine" on microcirculation in the rabbit ear. It was found that pulsed currents from the ELAV-8 device with a frequency of 100 Hz, as well as the biologically active agent "Pelamine" injected into the rabbit's paravertebral region by means of pulsed currents, have a vasodilatory effect on the vascular bed of the rabbit's ear. At the same time, transdermal administration of the biologically active agent "Pelamine" with the help of currents from the ELAV-8 device has a more prolonged effect on vasodilation. Key words: Microcirculation, rabbit ear, paravertebral region, vascular diameter, "Pelamine", ELAV-8 device.

Ibuprofen-Loaded Chitosan–Lipid Nanoconjugate Hydrogel with Gum Arabic: Green Synthesis, Characterisation, In Vitro Kinetics Mechanistic Release Study and PGE2 Production Test

Ibuprofen is a well-known non-steroidal anti-inflammatory (NSAID) medicine that is often used to treat inflammation in general. When given orally, it produces gastrointestinal issues which lead to lower patient compliance. Ibuprofen transdermal administration improves both patient compliance and the efficacy of the drug. Nanoconjugation hydrogels were proposed as a controlled transdermal delivery tool for ibuprofen. Six formulations were prepared using different compositions including chitosan, lipids, gum arabic, and polyvinyl alcohol, through ionic interaction, maturation, and freeze–thaw methods. The formulations were characterised by size, drug conjugation efficiency, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Further analysis of optimised hydrogels was performed, including X-ray diffraction (XRD), rheology, gel fraction and swelling ability, in vitro drug release, and in vitro macrophage prostaglandin E2 (PGE2) production testing. The effects of ibuprofen’s electrostatic interaction with a lipid or polymer on the physicochemical and dissolution characterisation of ibuprofen hydrogels were evaluated. The results showed that the S3 (with lipid conjugation) hydrogel provided higher conjugation efficiency and prolonged drug release compared with the S6 hydrogel.

Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy

Background Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. Results Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. Conclusions Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system. Graphical Abstract

In Vivo Visualization of Collagen Transdermal Absorption by a Combined Second-harmonic Generation and Two-photon Excited Fluorescence Method

The transdermal administration of collagen is an important method used for wound healing and skin regeneration. However, due to the limitations of previous approaches, the process and degree of collagen transdermal absorption could only be quantitatively and qualitatively assessed in vitro. In the present study, we introduced a novel approach combining second-harmonic generation with two-photon excited fluorescence to visualize the dynamics of collagen transdermal absorption in vivo. The high resolution images showed that the exogenous recombinant human collagen permeated through the epidermis, reached the dermis and formed reticular structures in real time. We also validated these findings through traditional in vitro skin scanning and histological examination. Thus, our approach provides a reliable method of measurement for the real-time evaluation of collagen absorption and treatment effects.

Optimizing glycerosome formulations via an orthogonal experimental design to enhance transdermal triptolide delivery

Triptolide exerts strong anti-inflammatory and immunomodulatory effects; however, its oral administration might be associated with side effects. Transdermal administration can improve the safety of triptolide. In this study, glycerosomes were prepared as the transdermal vehicle to enhance the transdermal delivery of triptolide. With entrapment efficiency and drug loading as dependent variables, the glycerosome formulation was optimized using an orthogonal experimental design. Phospholipid-to-cholesterol and phospholipid-to-triptolide mass ratios of 30:1 and 5:1, respectively and a glycerol concentration of 20 % (V/V) were used in the optimization. The glycerosomes prepared with the optimized formulation showed good stability, with an average particle size of 153.10 ± 2.69 nm, a zeta potential of –45.73 ± 0.60 mV and an entrapment greater than 75 %. Glycerosomes significantly increased the transdermal delivery of triptolide compared to conventional liposomes. As efficient carriers for the transdermal delivery of drugs, glycerosomes can potentially be used as an alternative to oral triptolide administration.

A Personalized FEM Model for Reproducible Measurement of Anti-inflammatory Drugs in Transdermal Administration to Knee

A personalized model of the human knee for enhancing the inter-individual reproducibility of a measurement method for monitoring Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) after transdermal delivery is proposed. The model is based on the solution of Maxwell Equations in the electric-quasi-stationary limit via Finite Element Analysis. The dimensions of the custom geometry are estimated on the basis of knee circumference at the patella, body mass index, and sex of each individual. An optimization algorithm allows to find out the electrical parameters of each subject by experimental impedance spectroscopy data. Muscular tissues were characterized anisotropically, by extracting Cole-Cole equation parameters from experimental data acquired with twofold excitation, both transversal and parallel to tissue fibers. A sensitivity and optimization analysis aiming at reducing computational burden in model customization achieved a worst-case reconstruction error lower than 5%. The personalized knee model and the optimization algorithm were validated in vivo by an experimental campaign on thirty volunteers, 67% healthy and 33% affected by knee osteoarthritis (Kellgren-Lawrence grade [1,4]), with an average error of 3%.