Advanced Therapeutics最新文献

Cover image provided courtesy of Yongheng Zhu, Xinghua Gao, Yuan Zhang, and co-workers.

T-cells forced through micro-sized pores become permeable, letting Chimeric Antigen Receptor (CAR) mRNA enter. The cells then express CAR proteins, gaining potent cancer-killing function. This method offers a path toward efficient, reproducible manufacturing and reduced therapy costs for patients. More details can be found in the Research Article by Cyrus W. Beh and co-workers (DOI: 2500094). Cover image by Ahmad Amirul Abdul Rahim.

In this study, a series of poly[(vinyl alcohol)-co-(2-acryloamido-2-methyl-1-propanesulfonic acid)] (PVA-co-PAMPS) copolymers is synthesized with varying PAMPS content (15–40 mol%) by free radical polymerization in water. These copolymers are used to elaborate asymmetric membranes by the phase inversion method. Incorporation of PAMPS significantly enhanced key membrane properties, including surface porosity, ion exchange capacity (IEC), and Young's modulus (up to 0.92 MPa), yielding biomaterials with mechanical properties similar to human skin. The membranes exhibited high swelling capacity in physiological fluids (up to 467%) and excellent enzymatic biodegradability (92% over 30 days). Increasing PAMPS content resulted in non-hemolytic surfaces, and conferred strong antibacterial activity against E. coli, achieving inhibition rates of 106–153% compared to gentamicin (40 ppm). Notably, membranes containing 20–30 mol% PAMPS showed selective cytotoxicity toward cervical and colon cancer cells, significantly inhibiting their proliferation up to 48 h, while promoting the proliferation of fibroblasts, monocytes, and osteoblasts. Moreover, membranes with 20 mol% PAMPS modulated inflammatory response in human monocytes by reducing the secretion of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1) cytokines and enhancing anti-inflammatory interleukin 10 (IL-10) cytokine production. These findings highlight PVA-co-PAMPS membranes as multifunctional platforms with potential for anticancer therapy, including implantable scaffolds, topical patches, and advanced in vitro cancer models.

Diabetes is a chronic disease that significantly impairs skin wound healing. There are not many efficient treatments to improve diabetic wound healing. Hydrogels are sustainable biomaterials used to release drugs on wound beds. In this study, a new hydrogel containing 3-hydroxytyrosol (HT) which is a polyphenol with antioxidant and anti-inflammatory properties was tested for its potential in diabetic wound healing. The hydrogel with HT presented a degradation rate of 99.8% at 24 h in vitro, a peak of HT release at 30 min, and higher scavenging activity at 24 h. In in vitro assays, the hydrogel with HT did not change the cell viability of fibroblasts and macrophages. The hydrogel with HT promoted cell migration and reduced lipid peroxidation in mouse fibroblasts under high glucose conditions. The hydrogel with HT also induced higher levels of interleukin-10 and heme oxygenase-1 under low and high glucose conditions in mouse macrophages. Topic application of hydrogel with HT augmented the collagen deposition and reduced the width of granulation tissue 7 days after wounding in diabetic mice. In conclusion, the hydrogel with HT is not cytotoxic, efficiently improves diabetic wound healing and it can be a promising therapeutic strategy for treatment of diabetic wounds.

Nanoformulation is often used to improve the solubility and uptake of bioactives; however, it also protects sensitive bioactives from chemical decomposition. A class of biocompatible emulsifiers created by conjugating hemp protein with green tea polyphenols is reported. A simple pH-assisted coupling protocol is employed to synthesize covalent and non-covalent conjugates, which are then used to produce 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) enriched hemp oil nanoemulsions (NEs) in water with an average droplet size of ca. 200 nm and ζ potential values of ca. −40 mV. The de novo emulsifiers protect the sensitive drug under conditions of simulated oxidative stress, an indication that the antioxidant properties of polyphenols are retained within the emulsifier. These emulsions are resistant to a wide variety of emulsion-breaking stressors and demonstrated remarkable colloidal stability over a period of 4 weeks with no evidence of phase separation. Fluorescence and confocal imaging confirmed cellular uptake of the formulation, while in vitro cytotoxicity assays showed acceptable cell viability with drug-loaded nanoemulsions. The sensitivity of 5-MeO-DMT mandates some form of formulation for reasonable bioavailability and reproducible dosages; our novel nanodelivery platform provides an elegant solution to this problem.

Effective and safe antibiotics active against pathogenic mycobacterial species are needed. Iron is an essential element for bacterial survival. Ga(NO₃)₃ (GN) and Ga protoporphyrin (GP) as iron mimetics have each been shown to inhibit the iron metabolism and growth of various mycobacterial species. In this study, the dual cyclodextrin nanoparticle (CDGPGN) is prepared that carries GP and GN using a sonication homogenization technique to increase the efficacy of the combination therapy. CDGPGN shows a long-acting antimicrobial activity against Mycobacteroides abscessus residing in monocyte-derived macrophages (MDM). A murine pulmonary study showed that the CDGPGN also inhibited the growth of M. abscessus and M. avium complex (MAC) in the lungs. GP induced mycobacterial superoxide dismutase (SOD) activity and reduced catalase activity. GN neither reduces nor increases SOD and catalase activities in mycobacteria. This study confirms that dual CDGPGN nanoparticles containing both GN and GP have potential for development as antimycobacterial agents against M. abscessus.

The development of efficient drug delivery systems for the treatment of inner ear diseases remains a significant challenge because of the intricate anatomy and physiology of the inner ear. Conventional in vitro and in vivo models are limited in their ability to accurately recapitulate the inner ear microenvironment and drug pharmacokinetics. The emergence of organ-on-chip technology provides a promising alternative for studying inner ear drug delivery by enabling the reconstruction of key inner ear barriers, such as the round window membrane, blood-labyrinth barrier, and perilymph-endolymph barrier, in a microfluidic platform. This review discusses the current strategies for inner ear drug delivery, the challenges associated with each approach, and the potential of an inner ear barrier organ chip to overcome these limitations. Incorporating relevant cell types, extracellular matrix components, and biomechanical cues, the inner ear organ chips offer a valuable platform for drug screening, efficacy assessment, and disease modeling. The validation of these models and their successful application in otologic drug development will require a multidisciplinary approach involving tissue engineering, microfabrication, and cell and molecular biology. As inner ear organ chip technology advances, it is expected to accelerate the development of targeted and efficient drug delivery systems for the treatment of hearing disorders.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of unknown origin that causes significant health problems worldwide. In this study, a fucose-anthocyanin conjugate is synthesized, and a colon-targeted drug delivery hydrogel is prepared. The components and structure of the hydrogel are characterized and identified. The findings reveal that the hydrogel containing the fucose-anthocyanin conjugate significantly reduced symptoms associated with dextran sulphate sodium (DSS)-induced colitis. Specifically, administration of the conjugate leads to reduced levels of pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β, thereby reducing the inflammatory response. Furthermore, administration of the conjugate restores intestinal barrier permeability by increasing mucin and tight junction protein levels. Additionally, the conjugate aided in rebalancing the intestinal microbiota in DSS-treated mice. This study sheds light on the therapeutic potential of the synthesized fucose-anthocyanin conjugate and its colon-targeted drug delivery hydrogel against colitis.

The existing antidepressant therapies are limited by efficacy gaps and adverse effects. Naturally derived ginsenosides including 20(S)-protopanaxadiol (PPD), exhibit promising antidepressant properties although issues like poor aqueous solubility and low oral bioavailability exist. This study developed and evaluated PPD-loaded PEG-PCL nanomicelles (Nano-PPD) in a murine model of corticosterone (CORT)-induced depression. Nano-PPD yields spherical nanoparticles with a uniform diameter of 165 nm. Pharmacokinetic studies revealed that Nano-PPD increased PPD bioavailability by ~3-fold and prolonged circulation time by 1.5-fold increase of Tmax compared with free PPD. In 21-day intervention of CORT-challenged C57BL/6J male mice, both PPD and Nano-PPD effectively alleviated depressive-like behaviors according to increased locomotor activity in the open field test and reduce immobility duration in forced swim and tail suspension tests. Nano-PPD outperformed free PPD at equivalent doses (p < 0.05). Mechanistically, Nano-PPD activated the ERK1/2 signaling pathway and upregulated BDNF expression in the prefrontal cortex with implications in mood regulation. Safety assessments confirmed that Nano-PPD did not alter the serum biomarker levels nor the histopathology in the liver and kidney. Collectively, these findings demonstrate that Nano-PPD possesses favorable pharmacokinetics and potent activity for modulating the neurotrophic pathways, representing a promising translational strategy for the prevention and treatment of depression.

https://doi.org/10.1002/adtp.202400084

In Figure 5C, the aPD-1/FCS and FBZ-BSA/FCS + aPD-1 (I.V.) groups on day 0, there was an overlap in the images of two mice. The reason is that when we took screenshots and saved them after analyzing the mouse imaging, the images were saved to the wrong folders. During our self-inspection, the software indicated that there was a risk of improper use of images, we immediately corrected the mistake by comparing it with the original data.

We apologize for this error.

Correction to “Figure 5C”

In Figure 5C, the problematic images appeared in the aPD-1/FCS group.

We apologize for this error.

The modified Figure 5C.