A Holographic-Type Model in the Description of Polymer-Drug Delivery Processes.

A unitary model of drug release dynamics is proposed, assuming that the polymer-drug system can be assimilated into a multifractal mathematical object. Then, we made a description of drug release dynamics that implies, via Scale Relativity Theory, the functionality of continuous and undifferentiable curves (fractal or multifractal curves), possibly leading to holographic-like behaviors. At such a conjuncture, the Schrödinger and Madelung multifractal scenarios become compatible: in the Schrödinger multifractal scenario, various modes of drug release can be "mimicked" (via period doubling, damped oscillations, modulated and "chaotic" regimes), while the Madelung multifractal scenario involves multifractal diffusion laws (Fickian and non-Fickian diffusions). In conclusion, we propose a unitary model for describing release dynamics in polymer-drug systems. In the model proposed, the polymer-drug dynamics can be described by employing the Scale Relativity Theory in the monofractal case or also in the multifractal one.

Theoretical-Experimental Approach of Chitosan/Quaternized Chitosan Nanofibers' Behavior in Wound Exudate Media.

This study aimed to investigate the behavior of chitosan/quaternized chitosan fibers in media mimicking wound exudates to understand their capacities as wound dressing. Fiber analysis of the fibers using dynamic vapor sorption proved their ability to adsorb moisture up to 60% and then to desorb it as a function of humidity, indicating their outstanding breathability. Dissolution analyses showed that quaternized chitosan leached from the fibers in water and PBS, whereas only small portions of chitosan were solubilized in water. In media containing lysozyme, the fibers degraded with a rate determined by their composition and pH, reaching a mass loss of up to 47% in media of physiologic pH. Notably, in media mimicking the wound exudate during healing, they adsorbed moisture even when their mass loss due to biodegradation was high, whereas they were completely degraded in the media of normal tissues, indicating bioabsorbable dressing capacities. A mathematical model was constructed, which characterized the degradation rate and morphology changes of chitosan/quaternized chitosan fibers through analyses of dynamics in scale space, using the Theory of Scale Relativity. The model was validated using experimental data, making it possible to generalize it to the degradation of other biopolymeric systems that address wound healing.

AI Evaluation of Imaging Factors in the Evolution of Stage-Treated Metastases Using Gamma Knife.

BACKGROUND: The study investigated whether three deep-learning models, namely, the CNN_model (trained from scratch), the TL_model (transfer learning), and the FT_model (fine-tuning), could predict the early response of brain metastases (BM) to radiosurgery using a minimal pre-processing of the MRI images. The dataset consisted of 19 BM patients who underwent stereotactic-radiosurgery (SRS) within 3 months. The images used included axial fluid-attenuated inversion recovery (FLAIR) sequences and high-resolution contrast-enhanced T1-weighted (CE T1w) sequences from the tumor center. The patients were classified as responders (complete or partial response) or non-responders (stable or progressive disease). METHODS: A total of 2320 images from the regression class and 874 from the progression class were randomly assigned to training, testing, and validation groups. The DL models were trained using the training-group images and labels, and the validation dataset was used to select the best model for classifying the evaluation images as showing regression or progression. RESULTS: Among the 19 patients, 15 were classified as "responders" and 4 as "non-responders". The CNN_model achieved good performance for both classes, showing high precision, recall, and F1-scores. The overall accuracy was 0.98, with an AUC of 0.989. The TL_model performed well in identifying the "progression" class, but could benefit from improved precision, while the "regression" class exhibited high precision, but lower recall. The overall accuracy of the TL_model was 0.92, and the AUC was 0.936. The FT_model showed high recall for "progression", but low precision, and for the "regression" class, it exhibited a high precision, but lower recall. The overall accuracy for the FT_model was 0.83, with an AUC of 0.885. CONCLUSIONS: Among the three models analyzed, the CNN_model, trained from scratch, provided the most accurate predictions of SRS responses for unlearned BM images. This suggests that CNN models could potentially predict SRS prognoses from small datasets. However, further analysis is needed, especially in cases where class imbalances exist.

Coherences in the Dynamics of Physical Systems from a Multifractal Perspective of Motion.

Using an analogy between the multi-fractal Schrödinger equation and the dumped oscillator equation through a special ansatz, Stoler-type coherences in the dynamics of physical systems are highlighted. Such a result implies a Ricatti-type gauge, a process that can be considered a calibration of the difference between the kinetic and potential energy of a Lagrangian, specified as a perfect square in generic coordinates.

Towards Multifractality through an Ernst-Type Potential in Complex Systems Dynamics.

Some possible correspondences between the Scale Relativity Theory and the Space-Time Theory can be established. Since both the multifractal Schrödinger equation from the Scale Relativity Theory and the General Relativity equations for a gravitational field with axial symmetry accept the same SL(2R)-type invariance, an Ernst-type potential (from General Relativity) and also a multi-fractal tensor (from Scale Relativity) are highlighted in the description of complex systems dynamics. In this way, a non-differentiable description of complex systems dynamics can become functional, even in the case of standard theories (General Relativity and Quantum Mechanics).

Theoretical and Experimental Aspects of Sodium Diclofenac Salt Release from Chitosan-Based Hydrogels and Possible Applications.

Two formulations based on diclofenac sodium salt encapsulated into a chitosan hydrogel were designed and prepared, and their drug release was investigated by combining in vitro results with mathematical modeling. To understand how the pattern of drug encapsulation impacted its release, the formulations were supramolecularly and morphologically characterized by scanning electron microscopy and polarized light microscopy, respectively. The mechanism of diclofenac release was assessed by using a mathematical model based on the multifractal theory of motion. Various drug-delivery mechanisms, such as Fickian- and non-Fickian-type diffusion, were shown to be fundamental mechanisms. More precisely, in a case of multifractal one-dimensional drug diffusion in a controlled-release polymer-drug system (i.e., in the form of a plane with a certain thickness), a solution that allowed the model's validation through the obtained experimental data was established. The present research reveals possible new perspectives, for example in the prevention of intrauterine adhesions occurring through endometrial inflammation and other pathologies with an inflammatory mechanism background, such as periodontal diseases, and also therapeutic potential beyond the anti-inflammatory action of diclofenac as an anticancer agent, with a role in cell cycle regulation and apoptosis, using this type of drug-delivery system.

The Cracking Behavior of Two Dental Composite Materials Validated through Multifractal Analyzes.

The aim of this in vitro study was to analyze, both experimentally and theoretically, the mechanical behavior of two types of composite materials used in restoring dental integrity. The samples of each composite resin, namely Filtek Supreme XT (3M ESPE, St. Paul, MN, USA) and Filtek Z250 (3M ESPE, St. Paul, MN, USA), were experimentally analyzed by determining their compressive strength and fracture behavior. The fractured fragments of the samples were subjected to surface evaluation by scanning electron microscopy. The compressive stress-compressive strain dependencies revealed stronger cracking of the Filtek Supreme XT composite than Filtek Z250 prior to fracture. Theoretically, the evaluation was made by means of holographic implementations of such types of composite materials. A Hooke-type equation in a differential form is presented, which links the proposed theoretical model with the experimentally obtained data.

Theoretical and Experimental Designs on Several Mechanical Properties of Cu-Al-Zn Shape Memory Alloys Used in the Processing Industry.

By assimilating shape memory alloys with mathematical multifractal-type objects, a theoretical model based on Scale Relativity Theory in the form of The Multifractal Theory of Motion, in order to explain the mechanical behavior of such material, is proposed. The model is validated by analyzing the mechanical behavior of Cu-Al-Zn shape memory alloy with various chemical compositions. More precisely, the multifractal tunnel effect can "mime" the mechanical hysteresis of such a material, a situation in which a direct correspondence for several mechanical properties of Cu-Al-Zn is highlighted (the chemical composition can be correlated with the shapes of the curves controlled through the multifractality degree, while the areas delimited by the same curves can be correlated with the multifractal specific potential, as a measure of the mechanical memory degree).

Drug Release from Nanoparticles (Polymeric Nanocapsules and Liposomes) Mimed through a Multifractal Tunnelling-Type Effect.

The present study analyzes (theoretically and experimentally) a drug release process from nanoparticles (polymeric nanocapsules and liposomes). This process is functionalized on the surface with an aptamer. These types of drug release processes can also be included in cream-type formulations. The obtained cream ensures the active targeting of tumor epithelial cells, in the case of skin cancer, because it can be easily administered to the skin by spreading, thus avoiding side effects caused by the toxicity of the drug to healthy cells, increasing both patient compliance and the effectiveness of the treatment. The process of obtaining these formulations is a simple one, easy to use and highly reproductible. The theoretical model, based on the multifractal tunnel effect within the Scale Relativity Theory, considers the system as a complex one. In this model, complexity is replaced with system multifractality, quantified in physical quantities as multifractal dimensions and multifractal functions. The main advantage of this approach consists in the fact that it allows us to obtain information on system behavior at a microscopic level and to evaluate microscopic characteristics of the system, such as intrinsic transparences of the drug molecules, multifractal constants as indicators of the system's complexity, the frequency of interactions within the system and the energy ratio between potential barrier energy and the energy of drug molecules.

Multi-fractal modeling of curcumin release mechanism from polymeric nanomicelles.

The physicochemical properties of "smart" or stimuli-sensitive amphiphilic copolymers can be modeled as a function of their environment. In special, pH-sensitive copolymers have practical applications in the biomedical field as drug delivery systems. Interactions between the structural units of any polymer-drug system imply mutual constraints at various scale resolutions and the nonlinearity is accepted as one of the most fundamental properties. The release kinetics, as a function of pH, of a model active principle, i.e., Curcumin, from nanomicelles obtained from amphiphilic pH-sensitive poly(2-vinylpyridine)-b-poly(ethylene oxide) (P2VP-b-PEO) tailor-made diblock copolymers was firstly studied by using the Rietger-Peppas equation. The value of the exponential coefficient, n, is around 0.5, generally suggesting a diffusion process, slightly disturbed in some cases. Moreover, the evaluation of the polymer-drug system's nonstationary dynamics was caried out through harmonic mapping from the usual space to the hyperbolic one. The kinetic model we developed, based on fractal theory, fits very well with the experimental data obtained for the release of Curcumin from the amphiphilic copolymer micelles in which it was encapsulated. This model is a variant of the classical kinetic models based on the formal kinetics of the process.

Drug-Loaded Polymeric Particulated Systems for Ophthalmic Drugs Release.

Drug delivery to the anterior or posterior segments of the eye is a major challenge due to the protection barriers and removal mechanisms associated with the unique anatomical and physiological nature of the ocular system. The paper presents the preparation and characterization of drug-loaded polymeric particulated systems based on pre-emulsion coated with biodegradable polymers. Low molecular weight biopolymers (chitosan, sodium hyaluronate and heparin sodium) were selected due to their ability to attach polymer chains to the surface of the growing system. The particulated systems with dimensions of 190-270 nm and a zeta potential varying from -37 mV to +24 mV depending on the biopolymer charges have been obtained. Current studies show that particles release drugs (dexamethasone/pilocarpine/bevacizumab) in a safe and effective manner, maintaining therapeutic concentration for a longer period of time. An extensive modeling study was performed in order to evaluate the drug release profile from the prepared systems. In a multifractal paradigm of motion, nonlinear behaviors of a drug delivery system are analyzed in the fractal theory of motion, in order to correlate the drug structure with polymer. Then, the functionality of a SL(2R) type "hidden symmetry" implies, through a Riccati type gauge, different "synchronization modes" (period doubling, damped oscillations, quasi-periodicity and intermittency) during the drug release process. Among these, a special mode of Kink type, better reflects the empirical data. The fractal study indicated more complex interactions between the angiogenesis inhibitor Bevacizumab and polymeric structure.

Update on the Use of Nanocarriers and Drug Delivery Systems and Future Directions in Cervical Cancer.

Cervical cancer represents a major health problem among females due to its increased mortality rate. The conventional therapies are very aggressive and unsatisfactory when it comes to survival rate, especially in terminal stages, which requires the development of new treatment alternatives. With the use of nanotechnology, various chemotherapeutic drugs can be transported via nanocarriers directly to cervical cancerous cells, thus skipping the hepatic first-pass effect and decreasing the rate of chemotherapy side effects. This review comprises various drug delivery systems that were applied in cervical cancer, such as lipid-based nanocarriers, polymeric and dendrimeric nanoparticles, carbon-based nanoparticles, metallic nanoparticles, inorganic nanoparticles, micellar nanocarriers, and protein and polysaccharide nanoparticles. Nanoparticles have a great therapeutic potential by increasing the pharmacological activity, drug solubility, and bioavailability. Through their mechanisms, they highly increase the toxicity in the targeted cervical tumor cells or tissues by linking to specific ligands. In addition, a nondifferentiable model is proposed through holographic implementation in the dynamics of drug delivery dynamics. As any hologram functions as a deep learning process, the artificial intelligence can be proposed as a new analyzing method in cervical cancer.

Infectious Inflammatory Processes and the Role of Bioactive Agent Released from Imino-Chitosan Derivatives Experimental and Theoretical Aspects.

The paper focuses on the development of a multifractal theoretical model for explaining drug release dynamics (drug release laws and drug release mechanisms of cellular and channel-type) through scale transitions in scale space correlated with experimental data. The mathematical model has been developed for a hydrogel system prepared from chitosan and an antimicrobial aldehyde via covalent imine bonds. The reversible nature of the imine linkage points for a progressive release of the antimicrobial aldehyde is controlled by the reaction equilibrium shifting to the reagents, which in turn is triggered by aldehyde consumption in the inhibition of the microbial growth. The development of the mathematical model considers the release dynamic of the aldehyde in the scale space. Because the release behavior is dictated by the intrinsic properties of the polymer-drug complex system, they were explained in scale space, showing that various drug release dynamics laws can be associated with scale transitions. Moreover, the functionality of a Schrödinger-type differential equation in the same scale space reveals drug release mechanisms of channels and cellular types. These mechanisms are conditioned by the intensity of the polymer-drug interactions. It was demonstrated that the proposed mathematical model confirmed a prolonged release of the aldehyde, respecting the trend established by in vitro release experiments. At the same time, the properties of the hydrogel recommend its application in patients with intrauterine adhesions (IUAs) complicated by chronic endometritis as an alternative to the traditional antibiotics or antifungals.

Langmuir Probe Perturbations during In Situ Monitoring of Pulsed Laser Deposition Plasmas.

The recent advancements in pulsed laser deposition (PLD) control via plasma diagnostics techniques have been positive and raised questions on the limitation of some techniques, such as the Langmuir probe (LP). The particularities of laser-produced plasma can lead to incorrect interpretation of collected electrical signal. In this paper, we explored the limitations of LP as a technique for in situ PLD control by performing investigations on several metallic plasmas, expanding in various Ar atmosphere conditions. Sub-microsecond modulation was seen in the reconstructed IV characteristics attributed to non-equilibrium dynamics of the ejected charges. A perturbative regime was recorded for Ar pressures higher than 2 Pa, where ionic bursts were observed in the electron saturation region. This perturbation was identified as a plasma fireball. A non-linear multifractal model was developed here to explore these new regimes of the LP. The strange attractors characterizing each fireball were reconstructed, and their evolution with the Ar pressure is discussed. Both short- and long-time non-linear behavior were correlated via probe bias, and the pressure effect on the strange attractor's defining the fireball-like behavior was investigated. A good correlation was noticed between the simulated data and experimental findings.

Implications and Consequences of SL(2R) as Invariance Group in the Description of Complex Systems Dynamics from a Multifractal Perspective of Motion.

Possible implications and consequences of using SL(2R) as invariance groups in the description at any scale resolution of the dynamics of any complex system are analyzed. From this perspective and based on Jaynes' remark (any circumstance left unspecified in the description of any complex system dynamics has the concrete expression in the existence of an invariance group), in the present paper one specifies such unspecified circumstances that result directly from the consideration of the canonical formalism induced by the SL(2R) as invariance group. It follows that both the Hamiltonian function and the Guassian distribution acquire the status of invariant group functions, the parameters that define the Hamiltonian acquire statistical significances based on a principle of maximizing informational energy, the class of statistical hypotheses specific to Gaussians of the same average acts as transitivity manifolds of the group (transitivity manifolds which can be correlated with the multifractal-non-multifractal scale transitions), joint invariant functions induced through SL(2R) groups isomorphism (the SL(2R) variables group, and the SL(2R) parameters group, etc.). For an ensemble of oscillators of the same frequency, the unspecified circumstances return to the ignorance of the amplitude and phase of each of the oscillators, which forces the recourse to a statistical ensemble traversed by the transformations of the Barbilian-type group. Finally, the model is validated based on numerical simulations and experimental results that refer to transient phenomena in ablation plasmas. The novelty of our model resides in the fact that fractalization through stochasticization is imposed through group invariance, situation in which the group's transitivity manifolds can be correlated with the scale resolution.

Impact of the Liquid Crystal Order of Poly(azomethine-sulfone)s on the Semiconducting Properties.

Organic semiconductors are an attractive class of materials with large application in various fields, from optoelectronics to biomedicine. Usually, organic semiconductors have low electrical conductivity, and different routes towards improving said conductivity are being investigated. One such method is to increase their ordering degree, which not only improves electrical conduction but promotes cell growth, adhesion, and proliferation at the polymer-tissue interface. The current paper proposes a mathematical model for understanding the influence of the ordering state on the electrical properties of the organic semiconductors. To this end, a series of aromatic poly(azomethine)s were prepared as thin films in both amorphous and ordered states, and their supramolecular and electrical properties were analyzed by polarized light microscopy and surface type cells, respectively. Furthermore, the film surface characteristics were investigated by atomic force microscopy. It was established that the manufacture of thin films from mesophase state induced an electrical conductivity improvement of one order of magnitude. A mathematical model was developed in the framework of a multifractal theory of motion in its Schrodinger representation. The model used the order degree of the thin films as a fractality measure of the physical system's representation in the multifractal space. It proposed two types of conductivity, which manifest at different ranges of fractalization degrees. The mathematical predictions were found to be in line with the empirical data.

The Landscape of Nanovectors for Modulation in Cancer Immunotherapy.

Immunotherapy represents a promising strategy for the treatment of cancer, which functions via the reprogramming and activation of antitumor immunity. However, adverse events resulting from immunotherapy that are related to the low specificity of tumor cell-targeting represent a limitation of immunotherapy's efficacy. The potential of nanotechnologies is represented by the possibilities of immunotherapeutical agents being carried by nanoparticles with various material types, shapes, sizes, coated ligands, associated loading methods, hydrophilicities, elasticities, and biocompatibilities. In this review, the principal types of nanovectors (nanopharmaceutics and bioinspired nanoparticles) are summarized along with the shortcomings in nanoparticle delivery and the main factors that modulate efficacy (the EPR effect, protein coronas, and microbiota). The mechanisms by which nanovectors can target cancer cells, the tumor immune microenvironment (TIME), and the peripheral immune system are also presented. A possible mathematical model for the cellular communication mechanisms related to exosomes as nanocarriers is proposed.

Manifest/Non-Manifest Drug Release Patterns from Polysaccharide Based Hydrogels-Case Study on Cyclodextrin-κ Carrageenan Crosslinked Hydrogels.

The aim of this study is to offer a comprehensive view on drug release from hydrogel, from both an experimental and a theoretical point of view. Aiming to benefit cyclodextrins' properties (not irritant; stable; able to modify the physical, chemical and biological properties of active compounds; accessible at low prices) and those of carrageenan polysaccharide (antitumor, immunomodulatory, antihyperlipidemic, anticoagulant, biocompatibility, biodegradability), original hydrogel films based on beta cyclodextrin and kappa carrageenan using epichlorohydrin as crosslinking agent were prepared and characterized from morphological and physical/chemical points of view. The results (morphology, the swelling degree, and the loading/release capacity) proved their potential as carriers for different types of drugs. Further, a new theoretical model, from a multifractal paradigm of motion, was proposed for the drug release from hydrogel films, starting from the fundaments of its evolution at a microscopic level, and aiming to obtain information on system evolution, at both the spatial and temporal scales, inapproachable by quantitative measurements.

Hydrogels Based on Alginates and Carboxymethyl Cellulose with Modulated Drug Release-An Experimental and Theoretical Study.

New hydrogels films crosslinked with epichlorohydrin were prepared based on alginates and carboxymethyl cellulose with properties that recommend them as potential drug delivery systems (e.g., biocompatibility, low toxicity, non-immunogenicity, hemostatic activity and the ability to absorb large amounts of water). The characterization of their structural, morphological, swelling capacity, loading/release and drug efficiency traits proved that these new hydrogels are promising materials for controlled drug delivery systems. Further, a new theoretical model, in the framework of Scale Relativity Theory, was built with to offer insights on the release process at the microscopic level and to simplify the analysis of the release process.

Prospects and Challenges of the Drug Delivery Systems in Endometriosis Pain Management: Experimental and Theoretical Aspects.

Endometriosis is considered a serious public health issue because of the large number of females affected by this illness. Chronic pain management in patients with endometriosis demands new strategies to increase the life quality of these patients. The development of drug delivery systems represents a new approach in pain treatment among endometriosis patients. Diclofenac sodium, one of the most utilized nonsteroidal anti-inflammatory drugs (NSAID), has its own limitations when being used in formulas such as oral, parental, or local applications. In this paper, a series of four drug release formulations based on chitosan, 2-hydroxy-5-nitrobenzaldehyde, and diclofenac sodium salt were prepared in view of the investigation of the drug release ability. The formulations were analyzed from a morphological and supramolecular point of view by scanning electron microscopy and polarized light microscopy. The in vitro drug release ability was investigated by mimicking a physiologic environment. A mathematical model, using the fractal paradigm of motion, is utilized to explain the behaviors of the drug delivery system presented in this paper. These results suggest a great potential of the proposed drug delivery system, based on chitosan and 2-hydroxy-5-nitrobenzaldehyde to improve the diclofenac sodium salt bioavailability, and it may represent a future treatment formula for endometriosis pain.