Advances in Research of Hydrogel Microneedle-Based Delivery Systems for Disease Treatment.

Microneedles (MNs), composed of multiple micron-scale needle-like structures attached to a base, offer a minimally invasive approach for transdermal drug delivery by penetrating the stratum corneum and delivering therapeutic agents directly to the epidermis or dermis. Hydrogel microneedles (HMNs) stand out among various MN types due to their excellent biocompatibility, high drug-loading capacity, and tunable drug-release properties. This review systematically examines the matrix materials and fabrication methods of HMN systems, highlighting advancements in natural and synthetic polymers, and explores their applications in treating conditions such as wound healing, hair loss, cardiovascular diseases, and cancer.

Newly Designed PCL-Wrapped Cryogel-Based Conduit Activated with IKVAV Peptide Derivative for Peripheral Nerve Repair.

The combination of macroporous cryogels with synthetic peptide factors represents a promising but poorly explored strategy for the development of extracellular matrix (ECM)-mimicking scaffolds for peripheral nerve (PN) repair. In this study, IKVAV peptide was functionalized with terminal lysine residues to allow its in situ cross-linking with gelatin macromer, resulting in the formation of IKVAV-containing proteinaceous cryogels. The controllable inclusion and distribution of the peptide molecules within the scaffold was verified using a fluorescently labelled peptide counterpart.

Host-Guest Complexation of Olmesartan Medoxomil by Heptakis(2,6-di-O-methyl)-β-cyclodextrin: Compatibility Study with Excipients.

Olmesartan medoxomil (OLM) is the prodrug of olmesartan, an angiotensin II type 1 receptor blocker that has antihypertensive and antioxidant activities and renal protective properties. It exhibits low water solubility, which leads to poor bioavailability and limits its clinical potential. To improve the solubility of OLM, a host-guest inclusion complex (IC) between heptakis(2,6-di-O-methyl)-β-cyclodextrin (DMβCD) and the drug substance was obtained.

Combinatorial Treatment with Praziquantel and Curcumin Reduces Parasite Burden and Clonorchiasis-Associated Pathologies in Rats.

: Clonorchiasis is a foodborne parasitic disease that can lead to severe biliary fibrosis and cholangiocarcinoma. While praziquantel (PZQ) is available for clonorchiasis treatment, it cannot revert the histopathological damage incurred through parasite-induced fibrosis. Curcumin (CUR) is an emerging experimental drug possessing anti-inflammatory and fibrosis-alleviating effects, thus signifying its potential as an anthelmintic drug.

Innovative Nanomedicine Delivery: Targeting Tumor Microenvironment to Defeat Drug Resistance.

Nanodrug delivery systems have revolutionized tumor therapy like never before. By overcoming the complexity of the tumor microenvironment (TME) and bypassing drug resistance mechanisms, nanotechnology has shown great potential to improve drug efficacy and reduce toxic side effects. This review examines the impact of the TME on drug resistance and recent advances in nanomedicine delivery systems to overcome this challenge.

Model-Based Dose Selection of a Sphingosine-1-Phosphate Modulator, Etrasimod, in Patients with Various Degrees of Hepatic Impairment.

Etrasimod is a newly FDA-approved Sphingosine-1-Phosphate modulator indicated for moderate and severe ulcerative colitis. It is extensively metabolized in the liver via the cytochrome P450 system and may accumulate markedly in patients with hepatic dysfunction, exposing them to toxicity. The aim of the current study is to utilize a physiologically-based pharmacokinetic modeling approach to evaluate the impact of hepatic impairment on the pharmacokinetic behavior of etrasimod and to appropriately select dosage regimens for patients with chronic liver disease; Methods: PK-Sim was used to develop the etrasimod PBPK model, which was verified using clinical data from healthy subjects and subsequently adapted to reflect the physiological changes associated with varying degrees of hepatic dysfunction; Results: Simulations indicated that hepatic clearance of etrasimod is clearly reduced in patients with Child-Pugh B and C liver impairment.

Targeted Antibacterial Endolysin to Treat Infected Wounds on 3D Full-Thickness Skin Model: XZ.700 Efficacy.

Skin wound healing is a physiological process orchestrated by epithelial and mesenchymal cells able to restore tissue continuity by re-organizing themselves and the ECM. This research study aimed to develop an optimized in vitro experimental model of full-thickness skin, to address molecular and morphological modifications occurring in the re-epithelization and wound healing process. Wound healing starting events were investigated within an experimental window of 8 days at the molecular level by gene expression and immunofluorescence of key epidermal and dermal biomarkers.

Novel Lipid Formulation Increases Absorption of Oral Cannabidiol (CBD).

: Cannabidiol (CBD) is an approved treatment for childhood epilepsies and a candidate treatment for several other CNS disorders. However, it has poor oral bioavailability. We investigated the effect of a novel lipid formulation on its absorption in humans and on its tissue distribution in mice.

Mesoporous Polydopamine Nano-Bowls Demonstrate a High Entrapment Efficiency and pH-Responsive Release of Paclitaxel for Suppressing A549 Lung Cancer Cell Proliferation In Vitro.

The effectiveness of paclitaxel (PTX) in treating non-small-cell lung carcinoma (NSCLC) is restricted by its poor pharmacokinetic profile and side effects. This limitation stems from the lack of a suitable delivery vector to efficiently target cancer cells. Therefore, there is a critical need to develop an efficient carrier for the optimised delivery of PTX in NSCLC therapy.

Improvement of End-of-Synthesis Radiochemical Purity of Lu-DOTA-PSMA-Ligands with Alternative Synthesis Approaches: Conversion Upswing and Side-Products Minimization.

Background: Radiochemical purity is a key criterion for the quality of radiopharmaceuticals used in clinical practice. The joint improvement of analytical methods capable of identifying related radiochemical impurities and determining the actual radiochemical purity, as well as the improvement of synthesis methods to minimize the formation of possible radiochemical impurities, is integral to the implementation of high-tech nuclear medicine procedures. PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for prostate cancer, and [Lu]Lu-PSMA-617 and [Lu]Lu-PSMA have achieved global recognition as viable radiopharmaceuticals.

Dendrimers, Dendrons, and the Dendritic State: Reflection on the Last Decade with Expected New Roles in Pharma, Medicine, and the Life Sciences.

This perspective begins with an overview of the major impact that the dendron, dendrimer, and dendritic state (DDDS) discovery has made on traditional polymer science. The entire DDDS technology is underpinned by an unprecedented new polymerization strategy referred to as step-growth, amplification-controlled polymerization (SGACP). This new SGACP paradigm allows for routine polymerization of common monomers and organic materials into precise monodispersed, dendritic macromolecules (i.

Population Pharmacokinetic and Pharmacodynamic Study of Palbociclib in Children and Young Adults with Recurrent, Progressive, or Refractory Brain Tumors.

Palbociclib, an oral CDK 4/6 inhibitor, was evaluated in a Pediatric Brain Tumor Consortium (PBTC) phase 1 (NCT02255461; PBTC-042) study to treat children and young adults with recurrent, progressive, or refractory brain tumors. The objectives of this study were to characterize the palbociclib population pharmacokinetics in children enrolled on PBTC-042, to conduct a population pharmacodynamic analysis in this patient population, and to perform a simulation study to assess the role of palbociclib exposure on neutropenia and thrombocytopenia. The palbociclib population pharmacokinetics and pharmacodynamics were characterized in this patient population (n = 34 patients; 4.

Systemic Embolism and Clinically Significant Bleeding Events in Older Adults with Nonvalvular Atrial Fibrillation After Treatment with Direct Oral Anticoagulants and Warfarin: A Retrospective Cohort Study in Japan.

Anticoagulant therapy, particularly the use of direct oral anticoagulant agents (DOACs), is recommended for patients with nonvalvular atrial fibrillation (NVAF). This multicenter observational retrospective cohort study aimed to assess the efficacy and safety of DOACs compared to warfarin in Japanese patients aged 75 years and older with NVAF. Data from the Mie-Life Innovation Promotion Center Database were used to collect medical information on the patients.

Development of a Population Pharmacokinetic Gabapentin Model Leveraging Therapeutic Drug Monitoring Concentrations.

Gabapentin has variable pharmacokinetics (PK), which contributes to difficulty in dosing and increased risk of adverse events. The objective of this study was to leverage gabapentin concentrations from therapeutic drug monitoring (TDM) to develop a population PK (popPK) model and characterize significant covariates that impact gabapentin PK. Data were retrospectively collected from 82 hospitalized adult patients with TDM gabapentin concentrations.

Bioactive Silk Revolution: Harnessing Curcuminoid Dye and Chitosan for Superior Antimicrobial Defence and UV Shielding.

Background/objectives: The use of natural colourants is gaining attention due to their biocompatibility and functional benefits. This study introduces a different approach using turmeric ( L.) dye extract combined with chitosan to significantly enhance the antibacterial and UV-shielding properties of silk.

Preparation and In Vitro/In Vivo Characterization of Mixed-Micelles-Loaded Dissolving Microneedles for Sustained Release of Indomethacin.

Indomethacin (IDM) is commonly used to treat chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis. However, long-term oral IDM treatment can harm the gastrointestinal tract. This study presents a design for encapsulating IDM within mixed micelles (MMs)-loaded dissolving microneedles (DMNs) to improve and sustain transdermal drug delivery.

Sustainable Carbon Dots Loaded into Carboxymethylcellulose Based Hydrogels for Uterine Cancer Bioimaging.

: The development of innovative materials for disease diagnostics and therapeutics is a fast-growing area of scientific research. In this work, we report the development of innovative hydrogels incorporating carbon dots (Cdots) for bioimaging purposes. : The Cdots were prepared using a sustainable and low-cost process, starting with an underused fiber from the Brazilian semiarid region.

The Use of Tissue Concentrations of Biological and Small-Molecule Therapies in Clinical Studies of Inflammatory Bowel Diseases.

The introduction of biological therapies has revolutionized inflammatory bowel disease (IBD) management. A critical consideration in developing these therapies is ensuring adequate drug concentrations at the site of action. While blood-based biomarkers have shown limited utility in optimizing treatment (except for TNF-alpha inhibitors and thiopurines), tissue drug concentrations may offer valuable insights.

Enhanced Ocular Bioavailability and Prolonged Duration via Hydrophilic Surface Nanocomposite Vesicles for Topical Drug Administration.

Background: Internal ocular diseases, such as macular edema, uveitis, and diabetic macular edema require precise delivery of therapeutic agents to specific regions within the eye. However, the eye's complex anatomical structure and physiological barriers present significant challenges to drug penetration and distribution. Traditional eye drops suffer from low bioavailability primarily due to rapid clearance mechanisms.

Biopharmaceutical Characterization and Stability of Nabumetone-Cyclodextrins Complexes Prepared by Grinding.

Nabumetone (NAB) is a poorly soluble nonsteroidal anti-inflammatory prodrug (BCS class II drug) whose solubility is significantly improved by complexation with cyclodextrins (CDs). : The solid complexes, in a 1:1 molar ratio, were prepared by mechanochemical activation by grinding, using β-cyclodextrin (β-CD) and its derivatives, hydroxypropyl- and sulfobutylether-β-cyclodextrin (HP-β-CD and SBE-β-CD). The complexation was confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and attenuated total reflectance Fourier-transformed infrared spectroscopy (ATR-FTIR).

3D-Printed Acrylated Soybean Oil Scaffolds with Vitrimeric Properties Reinforced by Tellurium-Doped Bioactive Glass.

In this study, we present novel, vitrimeric and biobased scaffolds that are designed for hard tissue applications, composed of acrylated, epoxidized soybean oil (AESO) and reinforced with bioactive glass that is Tellurium doped (BG-Te) and BG-Te silanized, to tune the mechanical and antibacterial properties. The manufacture's method consisted of a DLP 3D-printing method, enabling precise resolution and the possibility to manufacture a hollow and complex structure. The resin formulation was optimized with a biobased, reactive diluent to adjust the viscosity for an optimal 3D-printing process.

The Integration of Microwave-Synthesized Silver Colloidal Nanoparticles into Poly (Lactic Acid)-Based Textiles as Antimicrobial Agents via Pre- and Post-Electrospinning Processes.

This study introduces a novel method to enhance the antibacterial functionality of electrospun nanofibrous textiles by integrating silver nanoparticles (AgNPs) into poly (lactic acid) (PLA) fabrics through pre- and post-electrospinning techniques. AgNPs were incorporated into hydrophobic and modified hydrophilic PLA textiles via pre-solution blending and post-solution casting. A PEG-PPG-PEG tri-block copolymer was utilized to enhance hydrophilicity and water stability, while AgNPs served as antibacterial agents.

Current Positron Studies on the Modifications of the Molecular Packing in Green-Based Polymers Through Changes in the Synthesis Procedures or Environmental Conditions.

The sensitivity of positron annihilation characteristics to changes in the molecular packing in network-forming polymers has been demonstrated since the early 1980s. Positron annihilation lifetime spectroscopy (PALS) is a unique technique that can provide direct information on the free volume in polymers through the experimental parameters of the free volume hole distribution, their mean value, and volume fraction. This knowledge is currently applied for PALS investigations on the main processes that govern the molecular organization in some green polymers when subjected to different synthesis procedures or environmental conditions (humidity, physical aging, temperature).

The Influence of Fresh Latex Coagulation on the Parameter Characteristics of the Yeoh Hyperelastic Constitutive Model for Natural Rubber.

The coagulation of fresh latex is one of the critical processes that impacts rubber quality during natural rubber processing. Constitutive relationships are the basis for the study of the mechanical properties of rubber materials and serve as a prerequisite for material simulation studies. However, studies on the effect of different coagulation methods on natural rubber constitutive relationships have yet to be carried out, and the current models used for natural rubber constitutive relationships need to be improved.

The Catalytic Degradation of Waste PU and the Preparation of Recycled Materials.

In this paper, we investigated the efficient metal-free phosphorus-nitrogen (PN) catalyst and used the PN catalyst to degrade waste PU with two-component binary mixed alcohols as the alcohol solvent. We examined the effects of reaction temperature, time, and other factors on the hydroxyl value and viscosity of the degradation products; focused on the changing rules of the hydroxyl value, viscosity, and molecular weight of polyols recovered from degradation products with different dosages of the metal-free PN catalyst; and determined the optimal experimental conditions of reaction temperature 180 °C, reaction time 3 h, and PN dosage 0.08%.