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1.
ACS Appl Bio Mater ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530292

RESUMO

The discovery of specifically tailored therapeutic delivery systems has sparked the interest of pharmaceutical researchers considering improved therapeutic effectiveness and fewer adverse effects. The current study concentrates on the design and characterization of PLGA (polylactic-co-glycolic acid) capped mesoporous silica nanoparticles (MSN)-based systems for drug delivery for pH-sensitive controlled drug release in order to achieve a targeted drug release inside the acidic tumor microenvironment. The physicochemical properties of the nanoformulations were analyzed using TEM, zeta potential, AFM, TGA, FTIR, and BET analyses in addition to DLS size. The final formed PLGA-FoA-MSN-CAP and pure MSN had sizes within the therapeutic ranges of 164.5 ± 1.8 and 110.7 ± 2.2, respectively. Morphological characterization (TEM and AFM) and elemental analysis (FTIR and XPS) confirmed the proper capping and tagging of PLGA and folic acid (FoA). The PLGA-coated FoA-MSN exhibited a pH-dependent controlled release of the CAP (capecitabine) drug, showing efficient release at pH 6.8. Furthermore, the in vitro MTT test on PANC1 and MIAPaCa-2 resulted in an IC50 value of 146.37 µg/ml and 105.90 µg/ml, respectively. Mitochondrial-mediated apoptosis was confirmed from the caspase-3 and annexin V/PI flow cytometry assay, which displayed a cell cycle arrest at the G1 phase. Overall, the results predicted that the designed nanoformulation is a potential therapeutic agent in treating pancreatic cancer.

2.
Int J Pharm ; 659: 124238, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38768692

RESUMO

Burn wounds (BWs) with extensive blood loss, along with bacterial infections and poor healing, may become detrimental and pose significant rehabilitation obstacles in medical facilities. Therefore, the freeze-drying method synthesized novel hemocompatible chitosan, gelatin, and hyaluronic acid infused with graphene oxide-silymarin (CGH-SGO) hybrid constructs for application as a BW patch. Most significantly, synthesized hybrid constructs exhibited an interconnected-porous framework with precise pore sizes (≈118.52 µm) conducive to biological functions. Furthermore, the FTIR and XRD analyses document the constructs' physiochemical interactions. Similarly, enhanced swelling ratios, adequate WVTR (736 ± 78 g m-2 hr-1), and bio-degradation rates were seen during the physiological examination of constructs. Following the in vitro investigations, SMN-GO added to constructs improved their anti-bacterial (against E.coli and S. aureus), anti-oxidant, hemocompatible, and bio-compatible characteristics in conjunction with prolonged drug release. Furthermore, in vivo, implanting constructs on wounds exhibited significant acceleration in full-thickness burn wound (FT-BW) healing on the 14th day (CGH-SGO: 95 ± 2.1 %) in contrast with the control (Gauze: 71 ± 4.2 %). Additionally, contrary to gauze, the in vivo rat tail excision model administered with constructs assured immediate blood clotting. Therefore, CGH-SGO constructs with an improved porous framework, anti-bacterial activity, hemocompatibility, and biocompatibility could represent an attractive option for healing FT-BWs.


Assuntos
Antibacterianos , Queimaduras , Quitosana , Gelatina , Grafite , Ácido Hialurônico , Cicatrização , Ácido Hialurônico/química , Quitosana/química , Quitosana/administração & dosagem , Queimaduras/tratamento farmacológico , Queimaduras/terapia , Gelatina/química , Animais , Grafite/química , Grafite/administração & dosagem , Cicatrização/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Masculino , Ratos , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Ratos Wistar , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Antioxidantes/química
3.
Int J Biol Macromol ; 270(Pt 1): 132269, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744363

RESUMO

Burn wounds (BWs) cause impairment of native skin tissue and may cause significant microbial infections that demand immediate care. Curcumin (Cur) and quercetin (Que) exhibit antimicrobial, hemocompatibility, ROS-scavenging, and anti-inflammatory properties. However, its instability, water insolubility, and low biological fluid absorption render it challenging to sustain local Cur and Que doses at the wound site. Therefore, to combat these limitations, we employed blow-spinning and freeze-drying to develop a multi-layered, Cur/Que-loaded gelatin/chitosan/PCL (GCP-Q/C) nanofibroporous (NFP) matrix. Morphological analysis of the NFP-matrix using SEM revealed a well-formed multi-layered structure. The FTIR and XRD plots demonstrated dual-bioactive incorporation and scaffold polymer interaction. Additionally, the GCP-Q/C matrix displayed high porosity (82.7 ± 2.07 %), adequate pore size (∼121 µm), enhanced water-uptake ability (∼675 % within 24 h), and satisfactory biodegradation. The scaffolds with bioactives had a long-term release, increased antioxidant activity, and were more effective against gram-positive (S. aureus) and gram-negative (E. coli) bacteria than the unloaded scaffolds. The in vitro findings of GCP-Q/C scaffolds showed promoted L929 cell growth and hemocompatibility. Additionally, an in vivo full-thickness BW investigation found that an implanted GCP-Q/C matrix stimulates rapid recuperation and tissue regeneration. In accordance with the findings, the Gel/Ch/PCL-Que/Cur NFP-matrix could represent an effective wound-healing dressing for BWs.


Assuntos
Queimaduras , Curcumina , Nanofibras , Quercetina , Cicatrização , Curcumina/farmacologia , Curcumina/química , Cicatrização/efeitos dos fármacos , Quercetina/farmacologia , Quercetina/química , Animais , Porosidade , Nanofibras/química , Queimaduras/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/química , Ratos , Quitosana/química , Antioxidantes/farmacologia , Antioxidantes/química , Gelatina/química , Camundongos , Alicerces Teciduais/química , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Liberação Controlada de Fármacos
4.
Drug Discov Today ; 28(8): 103660, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37301249

RESUMO

Glypicans (GPCs) are generally involved in cellular signaling, growth and proliferation. Previous studies reported their roles in cancer proliferation. GPC1 is a co-receptor for a variety of growth-related ligands, thereby stimulating the tumor microenvironment by promoting angiogenesis and epithelial-mesenchymal transition (EMT). This work reviews GPC1-biomarker-assisted drug discovery by the application of nanostructured materials, creating nanotheragnostics for targeted delivery and application in liquid biopsies. The review includes details of GPC1 as a potential biomarker in cancer progression as well as a potential candidate for nano-mediated drug discovery.


Assuntos
Biomarcadores Tumorais , Neoplasias , Proliferação de Células , Neoplasias/tratamento farmacológico
5.
Front Med Technol ; 5: 1236107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37521721

RESUMO

Nanotechnology has become one of the most rapid, innovative, and adaptable sciences in modern science and cancer therapy. Traditional chemotherapy has limits owing to its non-specific nature and adverse side effects on healthy cells, and it remains a serious worldwide health issue. Because of their capacity to specifically target cancer cells and deliver therapeutic chemicals directly to them, nanoparticles have emerged as a viable strategy for cancer therapies. Nanomaterials disclose novel properties based on size, distribution, and shape. Biosynthesized or biogenic nanoparticles are a novel technique with anti-cancer capabilities, such as triggering apoptosis in cancer cells and slowing tumour growth. They may be configured to deliver medications or other therapies to specific cancer cells or tumour markers. Despite their potential, biosynthesized nanoparticles confront development obstacles such as a lack of standardisation in their synthesis and characterization, the possibility of toxicity, and their efficiency against various forms of cancer. The effectiveness and safety of biosynthesized nanoparticles must be further investigated, as well as the types of cancer they are most successful against. This review discusses the promise of biosynthesized nanoparticles as a novel approach for cancer therapeutics, as well as their mode of action and present barriers to their development.

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