Effervescent cannabidiol solid dispersion-doped dissolving microneedles for boosted melanoma therapy via the “TRPV1-NFATc1-ATF3” pathway and tumor microenvironment engineering DOI Creative Commons
Jiachen Shi,

Qiuling Ma,

Wenting Su

et al.

Biomaterials Research, Journal Year: 2023, Volume and Issue: 27(1)

Published: Feb. 9, 2023

Conventional dissolving microneedles (DMNs) face significant challenges in anti-melanoma therapy due to the lack of active thrust achieve efficient transdermal drug delivery and intra-tumoral penetration. In this study, effervescent cannabidiol solid dispersion-doped (Ef/CBD-SD@DMNs) composed combined components (CaCO3 & NaHCO3) CBD-based dispersion (CBD-SD) were facilely fabricated by "one-step micro-molding" method for boosted tumoral (CBD). Upon pressing into skin, Ef/CBD-SD@DMNs rapidly produce CO2 bubbles through proton elimination, significantly enhancing skin permeation penetration CBD. Once reaching tumors, can activate transient receptor potential vanilloid 1 (TRPV1) increase Ca2+ influx inhibit downstream NFATc1-ATF3 signal induce cell apoptosis. Additionally, raise pH environment trigger engineering tumor microenvironment (TME), including M1 polarization tumor-associated macrophages (TAMs) T cells infiltration. The introduction not only amplify effect but also provide sufficient with CBD potentiate efficacy. Such a "one stone, two birds" strategy combines advantages effects on TME regulation, creating favorable therapeutic conditions obtain stronger inhibition melanoma growth vitro vivo. This study holds promising offers facile tool therapies tumors.

Language: Английский

Cell-penetrating peptides for transmucosal delivery of proteins DOI Creative Commons
Jiamin Wu,

Sophie Roesger,

Natalie Jones

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 366, P. 864 - 878

Published: Jan. 27, 2024

Language: Английский

Citations

23
Milk Exosome–Liposome Hybrid Vesicles with Self-Adapting Surface Properties Overcome the Sequential Absorption Barriers for Oral Delivery of Peptides DOI

Peifu Xiao,

Hanxun Wang, Hongbing Liu

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(32), P. 21091 - 21111

Published: Aug. 5, 2024

Milk exosomes (mExos) have demonstrated significant promise as vehicles for the oral administration of protein and peptide drugs owing to their superior capacity traverse epithelial barriers. Nevertheless, certain challenges persist due intrinsic characteristics, including suboptimal drug loading efficiency, inadequate mucus penetration capability, susceptibility membrane loss. Herein, a hybrid vesicle with self-adaptive surface properties (mExos@DSPE-Hyd-PMPC) was designed by fusing functionalized liposomes natural mExos, aiming overcome limitations associated mExos unlock full potential in delivery. The property transformation mExos@DSPE-Hyd-PMPC achieved introducing pH-sensitive hydrazone bond between highly hydrophilic zwitterionic polymer phospholipids, utilizing pH microenvironment on jejunum surface. In comparison vesicles exhibited 2.4-fold enhancement encapsulation efficiency semaglutide (SET). neutrally charged surfaces jejunal lumen improved preservation proteins efficient traversal barrier. Upon reaching cells, retained positively efficiently overcame apical barrier, intracellular transport basolateral exocytosis resulted an bioavailability 8.7% notably enhanced pharmacological therapeutic effects. This study successfully addresses some holds overcoming sequential absorption barriers delivery peptides.

Language: Английский

Citations

22
Multi-material 3D printed eutectogel microneedle patches integrated with fast customization and tunable drug delivery DOI
Huan Liu,

Xinmeng Zhou,

Aminov Nail

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 368, P. 115 - 130

Published: Feb. 21, 2024

Language: Английский

Citations

21
The Current and Promising Oral Delivery Methods for Protein- and Peptide-Based Drugs DOI Open Access
Michał Nicze, Maciej Borówka,

Adrianna Dec

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 815 - 815

Published: Jan. 9, 2024

Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy patients diabetes mellitus over a century ago. Although the oral route of drug administration is preferred one by vast majority improves compliance, medications this kind due to their specific chemical structure are typically delivered parenterally, which ensures optimal bioavailability. In order overcome issues connected absorption PPs such as instability depending digestive enzymes pH changes gastrointestinal (GI) system hand, but also limited permeability across physiological barriers (mucus epithelium) other scientists strenuously searching for novel delivery methods enabling peptide protein drugs (PPDs) be administered enterally. These include utilization different nanoparticles, transport channels, substances enhancing permeation, modifications, hydrogels, microneedles, microemulsion, proteolytic enzyme inhibitors, cell-penetrating peptides, all extensively discussed review. Furthermore, article highlights PP therapeutics both previously currently available medical market.

Language: Английский

Citations

20
An antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo DOI Creative Commons
Huimin Kong, Chunxiong Zheng, Ke Yi

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 20, 2024

Abstract The membrane-fusion-based internalization without lysosomal entrapment is advantageous for intracellular delivery over endocytosis. However, protein corona formed on the membrane-fusogenic liposome surface converts its membrane-fusion performance to lysosome-dependent endocytosis, causing poorer efficiency in biological conditions. Herein, we develop an antifouling effective vivo. Leveraging specific lipid composition at optimized ratio, such facilitates fusion capacity even protein-rich conditions, attributed copious zwitterionic phosphorylcholine groups protein-adsorption resistance. Consequently, demonstrates robust membrane-fusion-mediated medium with up 38% fetal bovine serum, outclassing two traditional liposomes 4% and 6% concentrations. When injected into mice, can keep their membrane-fusion-transportation behaviors, thereby achieving efficient luciferase transfection enhancing gene-editing-mediated viral inhibition. This study provides a promising tool under complex physiological environments, enlightening future nanomedicine design.

Language: Английский

Citations

20
Microneedle‐Mediated Cell Therapy DOI Creative Commons

Ziqi Gao,

Tao Sheng, Wentao Zhang

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 11(8)

Published: Oct. 30, 2023

Microneedles have emerged as a promising platform for transdermal drug delivery with prominent advantages, such enhanced permeability, mitigated pain, and improved patient adherence. While microneedles primarily been employed delivering small molecules, nucleic acids, peptides, proteins, recent researches demonstrated their prospect in combination cell therapy. Cell therapy involving administration or transplantation of living cells (e.g. T cells, stem pancreatic cells) has gained significant attention preclinical clinical applications various disease treatments. However, the effectiveness systemic may be restricted localized conditions like solid tumors skin disorders due to limited penetration accumulation into lesions. In this perspective, an overview advances microneedle-assisted immunotherapy, tissue regeneration, hormone modulation, respect mechanical property, loading capacity, well viability bioactivity loaded is provided. Potential challenges future perspectives microneedle-mediated are also discussed.

Language: Английский

Citations

31
Lubricating Microneedles System with Multistage Sustained Drug Delivery for the Treatment of Osteoarthritis DOI
Kexin Chen, Yanlong Zhao, Weiwei Zhao

et al.

Small, Journal Year: 2024, Volume and Issue: 20(25)

Published: Jan. 15, 2024

Abstract Osteoarthritis (OA) is a typical joint degenerative disease that prevalent worldwide and significantly affects the normal activities of patients. Traditional treatments using diclofenac (DCF) as an anti‐inflammatory drug by oral administration transdermal delivery have many inherent deficiencies. In this study, lubricating microneedles (MNs) system for treatment osteoarthritis with multistage sustained great reduction in skin damage during MNs penetration developed. The bilayer dissolvable system, namely HA‐DCF@PDMPC, prepared designating composite material hyaluronic acid (HA) covalently conjugated compound (HA‐DCF) tips then modifying surface self‐adhesive copolymer (PDMPC). designed to achieve release DCF via ester bond hydrolysis, physical diffusion from tips, breakthrough lubrication coating. Additionally, reduced due presence coating on superficial surface. Therefore, show good compliance patch OA treatment, which validated cell tests therapeutic animal experiments, down‐regulating expression levels pro‐inflammatory factors alleviating articular cartilage destruction.

Language: Английский

Citations

12
An orally administered glucose-responsive polymeric complex for high-efficiency and safe delivery of insulin in mice and pigs DOI

Kangfan Ji,

Xiangqian Wei,

Anna R. Kahkoska

et al.

Nature Nanotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Language: Английский

Citations

12
Oral peptide therapeutics for diabetes treatment: State-of-the-art and future perspectives DOI Creative Commons

Bingwen Ding,

Zhu Zhu, Cong Guo

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(5), P. 2006 - 2025

Published: Feb. 28, 2024

Diabetes, characterized by hyperglycemia, is a major cause of death and disability worldwide. Peptides, such as insulin glucagon-like peptide-1 (GLP-1) analogs, have shown promise treatments for diabetes due to their ability mimic or enhance insulin's actions in the body. Compared subcutaneous injection, oral administration anti-diabetic peptides preferred approach. However, biological barriers significantly reduce efficacy peptide therapeutics. Recent advancements drug delivery systems formulation techniques greatly improved therapeutics treating diabetes. This review will highlight (1) benefits therapeutics; (2) delivery, including pH enzyme degradation, intestinal mucosa barrier, biodistribution barrier; (3) platforms overcome these barriers. Additionally, discuss prospects this field. The information provided serve valuable guide future developments

Language: Английский

Citations

11
High‐Strength Smart Microneedles with “Offensive and Defensive” Effects for Intervertebral Disc Repair DOI Open Access

Qingchen Meng,

En Xie, Heng Sun

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(2)

Published: Sept. 8, 2023

Intervertebral disc degeneration (IVDD) is a global public health issue. The injury of annulus fibrosus (AF) caused by acupuncture or discectomy can trigger IVDD again. However, there currently no suitable method for treating AF injury. In this study, the high-strength smart microneedles (MNs) which penetrate tissue through local and minimally invasive method, achieve remote control speeded-up release drug hyperthermia Near Infrared developed. PDA/GelMA composite MNs loaded with diclofenac sodium are designed to extracellularly "offend" inflammatory microenvironment mitigate damage cells, intracellularly increase level cytoprotective heat shock proteins enhance defense against hostile microenvironment, achieving "offensive defensive" effects. vitro experiments demonstrate that synergistic treatment photothermal therapy anti-inflammation effectively reduces inflammation, inhibits cell apoptosis, promotes synthesis extracellular matrix (ECM). vivo show response, promote ECM deposition, reduce restore biomechanical properties intervertebral (IVD) in rats. Overall, display promising effects provide new strategy IVD repair.

Language: Английский

Citations

23