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1.
ACS Appl Mater Interfaces ; 16(28): 36168-36193, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38954488

RESUMO

In the intricate landscape of Traumatic Brain Injury (TBI), the management of TBI remains a challenging task due to the extremely complex pathophysiological conditions and excessive release of reactive oxygen species (ROS) at the injury site and the limited regenerative capacities of the central nervous system (CNS). Existing pharmaceutical interventions are limited in their ability to efficiently cross the blood-brain barrier (BBB) and expeditiously target areas of brain inflammation. In response to these challenges herein, we designed novel mussel inspired polydopamine (PDA)-coated mesoporous silica nanoparticles (PDA-AMSNs) with excellent antioxidative ability to deliver a new potential therapeutic GSK-3ß inhibitor lead small molecule abbreviated as Neuro Chemical Modulator (NCM) at the TBI site using a neuroprotective peptide hydrogel (PANAP). PDA-AMSNs loaded with NCM (i.e., PDA-AMSN-D) into the matrix of PANAP were injected into the damaged area in an in vivo cryogenic brain injury model (CBI). This approach is specifically built while keeping the logic AND gate circuit as the primary focus. Where NCM and PDA-AMSNs act as two input signals and neurological functional recovery as a single output. Therapeutically, PDA-AMSN-D significantly decreased infarct volume, enhanced neurogenesis, rejuvenated BBB senescence, and accelerated neurological function recovery in a CBI.


Assuntos
Antioxidantes , Bivalves , Lesões Encefálicas Traumáticas , Indóis , Nanocompostos , Neurogênese , Estresse Oxidativo , Polímeros , Indóis/química , Indóis/farmacologia , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/metabolismo , Polímeros/química , Polímeros/farmacologia , Animais , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia , Nanocompostos/química , Bivalves/química , Neurogênese/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Dióxido de Silício/química , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Masculino
2.
AAPS PharmSciTech ; 25(6): 165, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009915

RESUMO

CaCO3 nanoparticles (nano-CaCO3) as nano-templates were prepared using CaCl2 and Na2CO3 solutions under controlled sonication (19.5 kHz). Using the same ultrasonic device, subsequently, hollow mesoporous silica nanoparticles (HMSNs) were obtained by the hard template of nano-CaCO3. HMSNs were selected as carriers for the antifungal drug voriconazole (VOR) loading to overcome poor water solubility. Three-dimensional CaCO3 nanosheets HMSNs were obtained under gentle sonication. Three-dimensional CaCO3 nanosheets of 24.5 nm (hydrodynamic diameter) were obtained under 17.6 W for 3 min. HMSNs were synthesized by double-template method with nano-CaCO3 as the hard template. Transmission electron microscopy measurements showed that the prepared HMSNs possess hollow structures with particle size between 110 and 120 nm. Nitrogen physisorption at -196 °C revealed that the HMSNs had high surface area (401.57 m2/g), high pore volume (0.11 cm3/g), and uniform pore size (2.22 nm) that facilitated the effective encapsulation of VOR in the HMSNs. The loading capacity of VOR (wt%) on the HMSNs was 7.96%, and the total VOR release amount of VOR-HMSNs material was 71.40% at 480 min. The kinetic model confirmed that the release mechanism of HMSNs nanoparticles followed Fickian diffusion at pH = 7.4 and 37 °C. Moreover, the cumulative VOR release at 42 °C (86.05%) was higher than that at 37 °C (71.40%). The cumulative release amount of VOR from the VOR-HMSNs material was 92.37% at pH = 5.8 at the same temperature. Both nano-CaCO3 templates and HMSNs were prepared by sonication at 19.5 kHz. The as-prepared HMSNs can effectively encapsulate VOR and released drug by Fickian diffusion.


Assuntos
Antifúngicos , Carbonato de Cálcio , Nanopartículas , Tamanho da Partícula , Dióxido de Silício , Voriconazol , Nanopartículas/química , Carbonato de Cálcio/química , Dióxido de Silício/química , Voriconazol/química , Voriconazol/administração & dosagem , Porosidade , Antifúngicos/administração & dosagem , Antifúngicos/química , Portadores de Fármacos/química , Solubilidade , Liberação Controlada de Fármacos , Sonicação/métodos
3.
J Control Release ; 373: 224-239, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39002796

RESUMO

Intravitreal injection of biodegradable implant drug carriers shows promise in reducing the injection frequency for neovascular retinal diseases. However, current intravitreal ocular devices have limitations in adjusting drug release rates for individual patients, thereby affecting treatment effectiveness. Accordingly, we developed mesoporous silica nanoparticles (MSNs) featuring a surface that reverse its charge in response to reactive oxygen species (ROS) for efficient delivery of humanin peptide (HN) to retinal epithelial cells (ARPE-19). The MSN core, designed with a pore size of 2.8 nm, ensures a high HN loading capacity 64.4% (w/w). We fine-tuned the external surface of the MSNs by incorporating 20% Acetyl-L-arginine (Ar) to create a partial positive charge, while 80% conjugated thioketal (TK) methoxy polyethylene glycol (mPEG) act as ROS gatekeeper. Ex vivo experiments using bovine eyes revealed the immobilization of Ar-MSNs-TK-PEG (mean zeta potential: 2 mV) in the negatively charged vitreous. However, oxidative stress reversed the surface charge to -25 mV by mPEG loss, facilitating the diffusion of the nanoparticles impeded with HN. In vitro studies showed that ARPE-19 cells effectively internalize HN-loaded Ar-MSNs-TK, subsequently releasing the peptide, which offered protection against oxidative stress-induced apoptosis, as evidenced by reduced TUNEL and caspase3 activation. The inhibition of retinal neovascularization was further validated in an in vivo oxygen-induced retinopathy (OIR) mouse model.

4.
J Dent Sci ; 19(3): 1506-1514, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39035341

RESUMO

Background/purpose: While there are numerous reports on surgical techniques and materials for bone grafting, limited methods are available to enhance the body's inherent capacity to heal bones. Here we investigated microRNA-199a (miR-199a), a molecular that promotes osteoblast differentiation and bone healing. Materials and methods: To construct a miR-199a delivery complex, miR-199a-5p mimics were coated with mesoporous silica nanoparticles (MSNs) following modified with polyethyleneimine (PEI) and peptide WEAKLAKALAKALAKHLAKALAKALKACEA (KALA) to obtain 199a-5p-loaded MSN-PEI-KALA. Nanoparticle complexes are assessed for particle size and zeta potential using transmission electron microscopy and dynamic light scattering. Then MC3T3-E1 cells are exposed to MSN_miR-199a-5p @PEI-KALA. The impact of MSN_miR-199a-5p@PEI-KALA at varying concentrations on cell viability is assessed using Cell Counting Kit-8. Cell uptake and distribution were analyzed by double fluorescent staining with fluorescein amidite-labeled MSN_miR-199a@PEI-KALA and lysosome labeling. On day 7 after osteogenic induction, alkaline phosphatase (ALP) staining was conducted. Results: The findings indicated that the nanoparticle complexes encapsulating PEI and peptide exhibited an augmentation in both particle size and zeta potential. At a dosage of 10 µg/mL, MSN_miR-199a@PEI-KALA displayed the lowest cytotoxicity compared to the control group. MC3T3-E1 cells treated with MSN_miR-199a-5p@PEI-KALA exhibited intensified ALP staining and elevated mRNA expression levels of ALP, runt-related transcription factor 2, and osteopontin, suggesting the involvement of miR-199a-5p-loaded MSN-PEI-KALA in osteogenic differentiation. Conclusion: The successful construction of the delivering complex MSN_miR-199a@PEI-KALA in present research highlights the promise of this biomaterial carrier for the application of miRNAs in treating bone defects.

5.
Mikrochim Acta ; 191(8): 477, 2024 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039391

RESUMO

A novel biofuel cell (BFC)-based self-powered electrochemical immunosensing platform was developed by integrating the target-induced biofuel release and biogate immunoassay for ultrasensitive 17ß-estradiol (E2) detection. The carbon nanocages/gold nanoparticle composite was employed in the BFCs device as the electrode material, through which bilirubin oxidase and glucose oxidase were wired to form the biocathode and bioanode, respectively. Positively charged mesoporous silica nanoparticles (PMSN) were encapsulated with glucose molecules as biofuel and subsequently coated by the negatively charged AuNPs-labelled anti-E2 antibody (AuNPs-Ab) serving as a biogate. The biogate could be opened efficiently and the trapped glucose released once the target E2 was recognized and captured by AuNPs-Ab due to the decreased adhesion between the antigen-antibody complex and PMSN. Then, glucose oxidase oxidized the glucose to produce a large number of electrons, resulting in significantly increased open-circuit voltage (EOCV). Promisingly, the proposed BFC-based self-powered immunosensor demonstrated exceptional sensitivity for the detection of E2 in the concentration range from 1.0 pg mL-1 to 10.0 ng mL -1, with a detection limit of 0.32 pg mL-1 (S/N = 3). Furthermore, the prepared BFC-based self-powered homogeneous immunosensor showed significant potential for implementation as a viable prototype for a mobile and an on-site bioassay system in food and environmental safety applications.


Assuntos
Fontes de Energia Bioelétrica , Técnicas Biossensoriais , Estradiol , Glucose Oxidase , Ouro , Limite de Detecção , Nanopartículas Metálicas , Imunoensaio/métodos , Estradiol/química , Estradiol/análise , Ouro/química , Glucose Oxidase/química , Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Humanos , Eletrodos , Glucose/análise , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química , Anticorpos Imobilizados/imunologia , Dióxido de Silício/química , Enzimas Imobilizadas/química
6.
J Photochem Photobiol B ; 258: 112977, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38991294

RESUMO

To solve the problems existing in the clinical application of hypericin (Hyp) and tirapazamine (TPZ), a nano-drug delivery system with synergistic anti-tumor functions was constructed using mesoporous silica nanoparticles (MSN) and sodium alginate (SA). The system exhibited excellent stability, physiological compatibility and targeted drug release performance in tumor tissues. In the in vitro and in vivo experiments, Hyp released from MSN killed tumor cells through photodynamic therapy (PDT). The degree of hypoxia in the tumor tissue site was exacerbated, enabling TPZ to fully exert its anti-tumor activity. Our studies suggested that the synergistic effects between the components of the nano-drug delivery system significantly improve the anti-tumor properties of Hyp and TPZ.

7.
Materials (Basel) ; 17(13)2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38998432

RESUMO

Mesoporous silica-based nanomaterials have emerged as multifunctional platforms with applications spanning catalysis, medicine, and nanotechnology. Since their synthesis in the early 1990s, these materials have attracted considerable interest due to their unique properties, including high surface area, tunable pore size, and customizable surface chemistry. This article explores the surface properties of a series of MSU-type mesoporous silica nanoparticles, elucidating the impact of different functionalization strategies on surface characteristics. Through an extensive characterization utilizing various techniques, such as FTIR, Z-potential, and nitrogen adsorption porosimetry, insights into the surface modifications of mesoporous silica nanoparticles are provided, contributing to a deeper understanding of their nanostructure and related interactions, and paving the way to possible unexpected actionability and potential applications.

8.
Carbohydr Res ; 543: 109206, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39002209

RESUMO

The objective of this study is to develop a drug carrier to overcome the inherent drawbacks of 5-Fluorouracil (5-Fu), including low bioavailability, short half-life, and systemic toxicity. In the present work, mesoporous silica nanoparticles (MSNs) capped by chitosan (CS) to encapsulate 5-Fu (5-Fu MSNs/CS) were fabricated by the sol-gel process, ultrasonic impregnation, and emulsion cross-linking. The 5-Fu MSNs/CS microspheres exhibit pH-responsive drug release and remarkable drug encapsulation capacity, as well as perfect sphericity, high specific surface area (680.62 cm2/g), and uniform particle size (2.64 ± 0.05 µm). The drug-loading content and encapsulation efficiency are 14.12 ± 0.53 % and 82.21 ± 2.13 %, respectively. The cumulative release of 5-Fu from MSNs/CS microspheres is fast and sustained at pH 5.0 (89.56 ± 0.97 %) compared to that at pH 7.4 (57.88 ± 0.91 %) in 96 h, and it is Fickian diffusion controlled. In conclusion, the MSNs/CS microspheres prepared in this study could be potential carriers for 5-Fu delivery.

9.
J Colloid Interface Sci ; 675: 1080-1090, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018635

RESUMO

Premature drug release in chemotherapy and hypoxic conditions in photodynamic therapy (PDT) are perplexing problems in tumor treatment. Thus, it is of great significance to develop the novel therapeutic system with controllable drug release and effective oxygen generation. Herein, a pH-responsive oxygen self-sufficient smart nanoplatform (named DHCCC), integrating hollow mesoporous silica nanoparticles (HMSNs), chitosan (CS), doxorubicin hydrochloride (DOX), chlorin e6 (Ce6) and catalase (CAT), is fabricated to enhance the tumor therapeutic efficacy efficiently through avoiding premature drug release and mitigating hypoxia of tumor microenvironment (TME). The drug DOX can be efficiently loaded into the HMSNs with large cavity and be controllable released because of the pH responsiveness of CS to the weak acidic TME, thereby elevating the chemotherapy efficacy. Meanwhile, CAT can catalyze the decomposition of endogenous hydrogen peroxide in situ generating oxygen to alleviate the hypoxia and enhance the PDT efficiency considerably. In vitro and in vivo results demonstrate that the combined chemo-photodynamic therapy based on the DHCCC nanoplatform exerts more effective antitumor efficacy than chemotherapy or PDT alone. The current study provides a promising inspiration to construct the pH-responsive oxygen self-sufficient smart nanomedicine with potentials to prevent premature drug leakage and overcome hypoxia for efficient tumor therapy.

10.
ACS Nano ; 18(29): 19283-19302, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38990194

RESUMO

Developing strategies to target injured pancreatic acinar cells (PACs) in conjunction with primary pathophysiology-specific pharmacological therapy presents a challenge in the management of acute pancreatitis (AP). We designed and synthesized a trypsin-cleavable organosilica precursor bridged by arginine-based amide bonds, leveraging trypsin's ability to selectively identify guanidino groups on arginine via Asp189 at the active S1 pocket and cleave the carboxy-terminal (C-terminal) amide bond via catalytic triads. The precursors were incorporated into the framework of mesoporous silica nanoparticles (MSNs) for encapsulating the membrane-permeable Ca2+ chelator BAPTA-AM with a high loading content (∼43.9%). Mesenchymal stem cell membrane coating and surface modification with PAC-targeting ligands endow MSNs with inflammation recruitment and precise PAC-targeting abilities, resulting in the highest distribution at 3 h in the pancreas with 4.7-fold more accumulation than that of naked MSNs. The outcomes transpired as follows: After bioinspired MSNs' skeleton biodegradation by prematurely and massively activated trypsin, BAPTA-AM was on-demand released in injured PACs, thereby effectively eliminating intracellular calcium overload (reduced Ca2+ level by 81.3%), restoring cellular redox status, blocking inflammatory cascades, and inhibiting cell necrosis by impeding the IκBα/NF-κB/TNF-α/IL-6 and CaMK-II/p-RIP3/p-MLKL/caspase-8,9 signaling pathways. In AP mice, a single dose of the formulation significantly restored pancreatic function (lipase and amylase reduced more by 60%) and improved the survival rate from 50 to 91.6%. The formulation offers a potentially effective strategy for clinical translation in AP treatment.


Assuntos
Pancreatite , Tripsina , Animais , Pancreatite/tratamento farmacológico , Pancreatite/patologia , Pancreatite/metabolismo , Tripsina/metabolismo , Tripsina/química , Camundongos , Porosidade , Nanomedicina , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Nanopartículas/química , Dióxido de Silício/química , Compostos de Organossilício/química , Compostos de Organossilício/farmacologia , Masculino , Humanos , Células Acinares/efeitos dos fármacos , Células Acinares/metabolismo , Células Acinares/patologia , Camundongos Endogâmicos C57BL
11.
Int J Nanomedicine ; 19: 7123-7136, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055375

RESUMO

Background: Drug therapy for eye diseases has been limited by multiple protective mechanisms of the eye, which can be improved using well-designed drug delivery systems. Mesoporous silica nanoparticles (MSNs) had been used in many studies as carriers of therapeutic agents for ocular diseases treatment. However, no studies have focused on ocular biosafety. Considering that MSNs containing tetrasulfur bonds have unique advantages and have drawn increasing attention in drug delivery systems, it is necessary to explore the ocular biosafety of tetrasulfur bonds before their widespread application as ophthalmic drug carriers. Methods: In this study, hollow mesoporous silica nanoparticles (HMSNs) with different tetrasulfur bond contents were prepared and characterized. The ocular biosafety of HMSN-E was evaluated in vitro on the three selected ocular cell lines, including corneal epithelial cells, lens epithelial cells and retinal endothelial cells (HREC), and in vivo by using topical eye drops and intravitreal injections. Results: In cellular experiments, HMSNs caused obvious S content-dependent cytotoxic effect. HMSNs with the highest tetrasulfur bond content (HMSN-E), showed the highest cytotoxicity among all the HMSNs, and HREC was the most vulnerable cell to HMSN-E. It was shown that HMSN-E could react with intracellular GSH to generate H2S and decrease intracellular GSH concentration. Treatment of HREC with HMSN-E increased intracellular ROS, decreased mitochondrial membrane potential, and induced cell cycle arrest at the G1/S checkpoint, finally caused apoptosis and necrosis of HREC. Topical eye drops of HMSN-E could cause corneal damage. The intravitreal injection of HMSN-E could induce inflammation in the vitreum and ganglion cell layers, resulting in vitreous opacities and retinal abnormalities. Conclusion: The incorporation of tetrasulfur bonds into HMSN can have toxic effects on ocular tissues. Therefore, when mesoporous silica nanocarriers are designed for ophthalmic pharmaceuticals, the ocular toxicity of the tetrasulfur bonds should be considered.


Assuntos
Nanopartículas , Dióxido de Silício , Humanos , Animais , Nanopartículas/química , Dióxido de Silício/química , Dióxido de Silício/toxicidade , Linhagem Celular , Porosidade , Portadores de Fármacos/química , Apoptose/efeitos dos fármacos , Coelhos , Sobrevivência Celular/efeitos dos fármacos , Olho/efeitos dos fármacos , Soluções Oftálmicas/química , Soluções Oftálmicas/farmacologia , Compostos de Organossilício/química , Compostos de Organossilício/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Injeções Intravítreas
12.
World J Clin Oncol ; 15(6): 667-673, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38946830

RESUMO

Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.

13.
Int J Nanomedicine ; 19: 6337-6358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946884

RESUMO

Background: It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research. Methods: First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo. Results: CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤120 µg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent. Conclusion: Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect.


Assuntos
Regeneração Óssea , Flavanonas , Nanopartículas , Osteoclastos , Dióxido de Silício , Flavanonas/química , Flavanonas/farmacologia , Flavanonas/farmacocinética , Flavanonas/administração & dosagem , Animais , Osteoclastos/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Dióxido de Silício/química , Concentração de Íons de Hidrogênio , Nanopartículas/química , Ratos , Camundongos , Ratos Sprague-Dawley , Quitosana/química , Masculino , Liberação Controlada de Fármacos , Porosidade , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Reabsorção Óssea/tratamento farmacológico , Células RAW 264.7 , Sistemas de Liberação de Medicamentos/métodos , Diferenciação Celular/efeitos dos fármacos
14.
Pharm Res ; 41(7): 1493-1505, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38918308

RESUMO

PURPOSE: Joint destruction is a major burden and an unsolved problem in rheumatoid arthritis (RA) patients. We designed an intra-articular mesoporous silica nanosystem (MSN-TP@PDA-GlcN) with anti-inflammatory and joint protection effects. The nanosystem was synthesized by encapsulating triptolide (TP) in mesoporous silica nanoparticles and coating it with pH-sensitive polydopamine (PDA) and glucosamine (GlcN) grafting on the PDA. The nano-drug delivery system with anti-inflammatory and joint protection effects should have good potency against RA. METHODS: A template method was used to synthesize mesoporous silica (MSN). MSN-TP@PDA-GlcN was synthesized via MSN loading with TP, coating with PDA and grafting of GlcN on PDA. The drug release behavior was tested. A cellular inflammatory model and a rat RA model were used to evaluate the effects on RA. In vivo imaging and microdialysis (MD) system were used to analyze the sustained release and pharmacokinetics in RA rats. RESULTS: TMSN-TP@PDA-GlcN was stable, had good biocompatibility, and exhibited sustained release of drugs in acidic environments. It had excellent anti-inflammatory effects in vitro and in vivo. It also effectively repaired joint destruction in vivo without causing any tissue toxicity. In vivo imaging and pharmacokinetics experiments showed that the nanosystem prolonged the residence time, lowered the Cmax value and enhanced the relative bioavailability of TP. CONCLUSIONS: These results demonstrated that MSN-TP@PDA-GlcN sustained the release of drugs in inflammatory joints and produced effective anti-inflammatory and joint protection effects on RA. This study provides a new strategy for the treatment of RA.


Assuntos
Anti-Inflamatórios , Artrite Reumatoide , Diterpenos , Liberação Controlada de Fármacos , Indóis , Nanopartículas , Fenantrenos , Polímeros , Dióxido de Silício , Animais , Dióxido de Silício/química , Artrite Reumatoide/tratamento farmacológico , Nanopartículas/química , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Fenantrenos/química , Fenantrenos/administração & dosagem , Fenantrenos/farmacocinética , Fenantrenos/farmacologia , Ratos , Diterpenos/administração & dosagem , Diterpenos/química , Diterpenos/farmacocinética , Diterpenos/farmacologia , Indóis/administração & dosagem , Indóis/química , Indóis/farmacocinética , Indóis/farmacologia , Polímeros/química , Porosidade , Masculino , Compostos de Epóxi/química , Compostos de Epóxi/administração & dosagem , Glucosamina/química , Glucosamina/administração & dosagem , Ratos Sprague-Dawley , Portadores de Fármacos/química , Humanos , Camundongos , Preparações de Ação Retardada , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle
15.
Carbohydr Polym ; 339: 122250, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823917

RESUMO

Glycyrrhizae Radix et rhizome/licorice is a precious herb in traditional Chinese medicine (TCM). TCM's polysaccharides are medicinally active. But herbal polysaccharides pose some limitations for topical applications. Therefore, this study aimed to utilize licorice polysaccharide via mesoporous silica nanoparticles (MSN) for anti-acne efficacy in topical delivery. The polysaccharide (GGP) was extracted with a 10 % NaOH solution. Chemical characterization suggested that GGP possesses an Mw of 267.9 kDa, comprised primarily of Glc (54.1 %) and Ara (19.12 %), and probably 1,4-linked Glc as a backbone. Then, MSN and amino-functionalized MSN were synthesized, GGP entrapped, and coated with polydopamine (PDA) to produce nanoparticle cargo. The resulted product exhibited 76 % entrapment efficiency and an in vitro release of 89 % at pH 5, which is usually an acne-prone skin's pH. Moreover, it significantly increased Sebocytes' cellular uptake. GGP effectively acted as an anti-acne agent and preserved its efficacy in synthesized nanoparticles. In vivo, the results showed that a 20 % gel of MSN-NH2-GGP@PDA could mediate an inflammatory response via inhibiting pro-inflammatory cytokines and regulating anti-inflammatory cytokines. The MSN-NH2-GGP@PDA inhibited TLR2-activated-MAPK and NF-κB pathway triggered by heat-killed P. acnes. In conclusion, fabricated MSN entrapped GGP for biomimetic anti-acne efficacy in topical application.


Assuntos
Acne Vulgar , Glycyrrhiza , Nanopartículas , Polissacarídeos , Dióxido de Silício , Glycyrrhiza/química , Dióxido de Silício/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Nanopartículas/química , Animais , Porosidade , Acne Vulgar/tratamento farmacológico , Camundongos , Administração Tópica , Humanos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Indóis , Polímeros
16.
Int J Nanomedicine ; 19: 5441-5458, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38868593

RESUMO

Introduction: Quercetin (QUER), a flavonoid abundant in fruits and vegetables, is emerging as a promising alternative therapeutic agent for obesity treatment due to its antioxidant and anti-adipogenic properties. However, the clinical application of QUER is limited by its poor solubility, low bioavailability, and potential toxicity at high doses. To address these challenges, this study aims to develop an advanced drug delivery system using fluorescent mesoporous silica nanoparticles (FMSNs) coated with polydopamine (PDA) for the efficient and sustained delivery of QUER to inhibit adipogenesis. Methods: The research included the synthesis of PDA-coated FMSNs for encapsulation of QUER, characterization of their mesoporous structures, and systematic investigation of the release behavior of QUER. The DPPH assay was used to evaluate the sustained radical scavenging potential. Concentration-dependent effects on 3T3-L1 cell proliferation, cellular uptake and adipogenesis inhibition were investigated. Results: PDA-coated FMSNs exhibited well-aligned mesoporous structures. The DPPH assay confirmed the sustained radical scavenging potential, with FMSNs-QUER@PDA showing 53.92 ± 3.48% inhibition at 72 h, which was higher than FMSNs-QUER (44.66 ± 0.57%) and free QUER (43.37 ± 5.04%). Concentration-dependent effects on 3T3-L1 cells highlighted the enhanced efficacy of PDA-coated FMSNs for cellular uptake, with a 1.5-fold increase compared to uncoated FMSNs. Adipogenesis inhibition was also improved, with relative lipid accumulation of 44.6 ± 4.6%, 37.3 ± 4.6%, and 36.5 ± 7.3% at 2.5, 5, and 10 µM QUER concentrations, respectively. Conclusion: The study successfully developed a tailored drug delivery system, emphasizing sustained QUER release and enhanced therapeutic effects. FMSNs, especially when coated with PDA, exhibit promising properties for efficient QUER delivery, providing a comprehensive approach that integrates advanced drug delivery technology and therapeutic efficacy.


Assuntos
Células 3T3-L1 , Adipogenia , Preparações de Ação Retardada , Portadores de Fármacos , Indóis , Nanopartículas , Polímeros , Quercetina , Dióxido de Silício , Quercetina/química , Quercetina/farmacologia , Quercetina/farmacocinética , Quercetina/administração & dosagem , Animais , Camundongos , Adipogenia/efeitos dos fármacos , Dióxido de Silício/química , Indóis/química , Indóis/farmacologia , Indóis/farmacocinética , Indóis/administração & dosagem , Nanopartículas/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/farmacocinética , Portadores de Fármacos/química , Polímeros/química , Porosidade , Liberação Controlada de Fármacos , Proliferação de Células/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/farmacocinética , Antioxidantes/administração & dosagem
17.
Eur J Pharm Biopharm ; 201: 114349, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38848782

RESUMO

Nanocarriers have demonstrated promising potential in the delivery of various anticancer drugs and in improving the efficiency of the treatment. In this study, silver nanoparticles (AgNPs) were green-synthesized using the extracts of different parts of the pomegranate plant, including the peel, flower petals, and calyx. To obtain the most efficient extract used for the green synthesis of AgNPs, all three types of synthesized nanoparticles were characterized. Then, (3-Aminopropyl) triethoxysilane-functionalized mesoporous silica nanoparticles (MSNs-APTES) decorated with AgNPs were fabricated via a one-pot green-synthesis method. AgNPs were directly coated on the surface of MSNs-APTES by adding pomegranate extract enriched with a source of reducing agent leading to converting the silver ion to AgNPs. The MSN-APTES-AgNPs (MSNs-AgNPs) have been thoroughly characterized using nanoparticle characterization techniques. In addition, DNA cleavage and hemolysis activities of the synthesized nanoparticles were analyzed, confirming the biocompatibility of synthesized nanoparticles. The Doxorubicin (DOX, as a breast/cervical anti-cancer drug) loading (42.8%) and release profiles were investigated via UV-visible spectroscopy. The fibroblast, breast cancer, and cervical cancer cells' viability against DOX-loaded nanoparticles were also studied. The results of this high drug loading, uniform shape, and small functionalized nanoparticles demonstrated its great potential for breast and cervical cancer management.


Assuntos
Neoplasias da Mama , Doxorrubicina , Nanopartículas Metálicas , Dióxido de Silício , Prata , Neoplasias do Colo do Útero , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Humanos , Dióxido de Silício/química , Prata/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Nanopartículas Metálicas/química , Porosidade , Portadores de Fármacos/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Punica granatum/química , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Aminas/química , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Células MCF-7 , Células HeLa , Animais , Liberação Controlada de Fármacos
18.
Int J Pharm ; 660: 124314, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38862066

RESUMO

Mesoporous silica nanoparticles (MSNs) endowed with polymer coatings present a versatile platform, offering notable advantages such as targeted, pH-controlled, and stimuli-responsive drug delivery. Surface functionalization, particularly through amine and carboxyl modification, enhances their suitability for polymerization, thereby augmenting their versatility and applicability. This review delves into the diverse therapeutic realms benefiting from polymer-coated MSNs, including photodynamic therapy (PDT), photothermal therapy (PTT), chemotherapy, RNA delivery, wound healing, tissue engineering, food packaging, and neurodegenerative disorder treatment. The multifaceted potential of polymer-coated MSNs underscores their significance as a focal point for future research endeavors and clinical applications. A comprehensive analysis of various polymers and biopolymers, such as polydopamine, chitosan, polyethylene glycol, polycaprolactone, alginate, gelatin, albumin, and others, is conducted to elucidate their advantages, benefits, and utilization across biomedical disciplines. Furthermore, this review extends its scope beyond polymerization and biomedical applications to encompass topics such as surface functionalization, chemical modification of MSNs, recent patents in the MSN domain, and the toxicity associated with MSN polymerization. Additionally, a brief discourse on green polymers is also included in review, highlighting their potential for fostering a sustainable future.


Assuntos
Nanopartículas , Polímeros , Dióxido de Silício , Dióxido de Silício/química , Nanopartículas/química , Humanos , Polímeros/química , Animais , Porosidade , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/química
19.
Biomater Adv ; 162: 213922, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38878645

RESUMO

Mesoporous silica nanoparticles were synthesized using a microemulsion-assisted sol-gel method, and calcium, gallium or a combination of both, were used as dopants. The influence of these metallic ions on the physicochemical properties of the nanoparticles was investigated by scanning and transmission electron microscopy, as well as N2 adsorption-desorption methods. The presence of calcium had a significant impact on the morphology and textural features of the nanoparticles. The addition of calcium increased the average diameter of the nanoparticles from 80 nm to 150 nm, while decreasing their specific surface area from 972 m2/g to 344 m2/g. The nanoparticles of all compositions were spheroidal, with a disordered mesoporous structure. An ion release study in cell culture medium demonstrated that gallium was released from the nanoparticles in a sustained manner. In direct contact with concentrations of up to 100 µg/mL of the nanoparticles, gallium-containing nanoparticles did not exhibit cytotoxicity towards pre-osteoblast MC3T3-E1 cells. Moreover, in vitro cell culture tests revealed that the addition of gallium to the nanoparticles enhanced osteogenic activity. Simultaneously, the nanoparticles disrupted the osteoclast differentiation of RAW 264.7 macrophage cells. These findings suggest that gallium-containing nanoparticles possess favorable physicochemical properties and biological characteristics, making them promising candidates for applications in bone tissue regeneration, particularly for unphysiological or pathological conditions such as osteoporosis.


Assuntos
Gálio , Nanopartículas , Osteoclastos , Osteogênese , Gálio/química , Gálio/farmacologia , Animais , Camundongos , Osteoclastos/efeitos dos fármacos , Nanopartículas/química , Osteogênese/efeitos dos fármacos , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Células RAW 264.7 , Porosidade , Diferenciação Celular/efeitos dos fármacos
20.
Ther Deliv ; 15(6): 449-462, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38888579

RESUMO

Aim: The study was aimed to formulate and evaluate apremilast-loaded zinc oxide-mesoporous silica nanoparticles for treatment of psoriasis. Materials & methods: Mesoporous silica nanoparticles were prepared by using sol-gel method and evaluated for particle size, in vitro drug release, in vitro cytotoxicity study and in vivo pharmacodynamic study. Results: The synthesized mesoporous silica nanoparticles showed particle size of 319.9 ± 3.9 nm, with 24 ± 0.217% of loading capacity. In vitro cytotoxicity study on A-431 cell line showed increased anti-psoriatic activity of apremilast-loaded zinc oxide-mesoporous silica nanoparticles. In vivo pharmacodynamic study and histological studies showed improved efficacy of drug in imiquimod-induced psoriasis mice model. Conclusion: The apremilast-loaded zinc oxide-mesoporous silica nanoparticles showed improved therapeutic efficacy, suggesting that they are promising approach for topical treatment of psoriasis.


[Box: see text].


Assuntos
Liberação Controlada de Fármacos , Nanopartículas , Psoríase , Dióxido de Silício , Talidomida , Óxido de Zinco , Psoríase/tratamento farmacológico , Óxido de Zinco/química , Óxido de Zinco/administração & dosagem , Animais , Dióxido de Silício/química , Dióxido de Silício/administração & dosagem , Nanopartículas/química , Camundongos , Humanos , Talidomida/análogos & derivados , Talidomida/administração & dosagem , Talidomida/farmacologia , Talidomida/química , Tamanho da Partícula , Portadores de Fármacos/química , Porosidade , Imiquimode/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Modelos Animais de Doenças
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