pH dependent delivery of chlorhexidine from PLGA grafted mesoporous silica nanoparticles at resin-dentin interface

Abstract Background: A low pH environment is created due to the production of acids by oral biofilms that further leads to the dissolution of hydroxyapatite crystal in the tooth structure significantly altering the equilibrium. Although the overall bacterial counts may not be eradicated from the oral cavity, however, synthesis of engineered anti-bacterial materials are warranted to reduce the pathogenic impact of the oral biofilms. The purpose of this study was to synthesize and characterize chlorhexidine (CHX)-loaded mesoporous silica nanoparticles (MSN) grafted with poly-L-glycolic acid (PGA) and to test the in vitro drug release in various pH environments, cytotoxicity, and antimicrobial capacity. In addition, this study aimed to investigate the delivery of CHX-loaded/MSN-PGA nanoparticles through demineralized dentin tubules and how these nanoparticles interact with tooth dentin after mixing with commercial dentin adhesive for potential clinical application.Results: Characterization using SEM/TEM and EDX confirmed the synthesis of CHX-loaded/MSN-PGA. An increase in the percentage of drug encapsulation efficiency from 81% to 85% in CHX loaded/MSN and 92% to 95% in CHX loaded/MSN-PGA proportionately increased with increasing the amount of CHX during the fabrication of nanoparticles. For both time-periods (24 h or 30 Days), the relative microbial viability significantly decreased by increasing the CHX content (P<0.001). Generally, the cell viability percentage of DPSCs exposed to MSN-PGA/Blank, CHX-loaded/MSN, and CHX-loaded/MSN-PGA, respectively was >80% indicating low cytotoxicity profiles of experimental nanoparticles. After 9 months in artificial saliva (pH 7.4), the significantly highest micro-tensile bond strength value was recorded for 25:50 CHX/MSN and 25:50:50 CHX/MSN-PGA. A homogenous and widely distributed 50:50:50 CHX-loaded/MSN-PGA nanoparticles exhibited excellent bonding with the application of commercially available dentin adhesive.Conclusions: A pH-sensitive CHX release response was noted when loaded in MSN grafted PGA nanoparticles. The formulated drug-loaded nanocarrier demonstrated excellent physicochemical, spectral, and biological characteristics. Showing considerable capacity to penetrate effectively inside dentinal tubules and having high antibacterial efficacy, this system could be potentially used in adhesive and restorative dentistry.

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pH-dependent delivery of chlorhexidine from PGA grafted mesoporous silica nanoparticles at resin-dentin interface

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00788-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Zohaib Akram ◽

Sultan Aati ◽

Hein Ngo ◽

Amr Fawzy

Keyword(s):

Mesoporous Silica ◽

Silica Nanoparticles ◽

Artificial Saliva ◽

Mesoporous Silica Nanoparticles ◽

Tooth Structure ◽

Oral Biofilms ◽

Viability Percentage ◽

Low Cytotoxicity ◽

Dentin Adhesive

Abstract Background A low pH environment is created due to the production of acids by oral biofilms that further leads to the dissolution of hydroxyapatite crystal in the tooth structure significantly altering the equilibrium. Although the overall bacterial counts may not be eradicated from the oral cavity, however, synthesis of engineered anti-bacterial materials are warranted to reduce the pathogenic impact of the oral biofilms. The purpose of this study was to synthesize and characterize chlorhexidine (CHX)-loaded mesoporous silica nanoparticles (MSN) grafted with poly-L-glycolic acid (PGA) and to test the in vitro drug release in various pH environments, cytotoxicity, and antimicrobial capacity. In addition, this study aimed to investigate the delivery of CHX-loaded/MSN-PGA nanoparticles through demineralized dentin tubules and how these nanoparticles interact with tooth dentin after mixing with commercial dentin adhesive for potential clinical application. Results Characterization using SEM/TEM and EDX confirmed the synthesis of CHX-loaded/MSN-PGA. An increase in the percentage of drug encapsulation efficiency from 81 to 85% in CHX loaded/MSN and 92–95% in CHX loaded/MSN-PGA proportionately increased with increasing the amount of CHX during the fabrication of nanoparticles. For both time-periods (24 h or 30 days), the relative microbial viability significantly decreased by increasing the CHX content (P < 0.001). Generally, the cell viability percentage of DPSCs exposed to MSN-PGA/Blank, CHX-loaded/MSN, and CHX-loaded/MSN-PGA, respectively was > 80% indicating low cytotoxicity profiles of experimental nanoparticles. After 9 months in artificial saliva (pH 7.4), the significantly highest micro-tensile bond strength value was recorded for 25:50 CHX/MSN and 25:50:50 CHX/MSN-PGA. A homogenous and widely distributed 50:50:50 CHX-loaded/MSN-PGA nanoparticles exhibited excellent bonding with the application of commercially available dentin adhesive. Conclusions A pH-sensitive CHX release response was noted when loaded in MSN grafted PGA nanoparticles. The formulated drug-loaded nanocarrier demonstrated excellent physicochemical, spectral, and biological characteristics. Showing considerable capacity to penetrate effectively inside dentinal tubules and having high antibacterial efficacy, this system could be potentially used in adhesive and restorative dentistry.

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pH Dependent Delivery of Chlorhexidine From PLGA Grafted Mesoporous Silica Nanoparticles at Resin-Dentin Interface

10.21203/rs.3.rs-123608/v1 ◽

2020 ◽

Author(s):

Zohaib Akram ◽

Sultan Aati ◽

Hein Ngo ◽

Amr Fawzy

Keyword(s):

Mesoporous Silica ◽

Artificial Saliva ◽

Mesoporous Silica Nanoparticles ◽

Plga Nanoparticles ◽

Tooth Structure ◽

Oral Biofilms ◽

Viability Percentage ◽

Low Cytotoxicity ◽

Dentin Adhesive

Abstract Background: A low pH environment is created due to the production of acids by oral biofilms that further leads to the dissolution of hydroxyapatite crystal in the tooth structure significantly altering the equilibrium. Although the overall bacterial counts may not be eradicated completely from the oral cavity, however, synthesis of engineered anti-bacterial materials are warranted in order to reduce the pathogenic impact of the oral biofilms. The purpose of this study was to synthesize and characterize chlorhexidine-loaded mesoporous silica nanoaprticles (MSN) grafted with poly-L-glycolic acid (PLGA) and to test the in vitro drug release in various pH environments, cytotoxicity, and antimicrobial capacity. In addition, to investigate the delivery of CHX-loaded/MSN-PLGA through dentin tubules of demineralized dentin substrates and the interaction of these nanoparticles with commercial dentin adhesive after applying it on demineralized substrates for potential clinical application.Results: Characterization using SEM/TEM and EDX confirmed the synthesis of CHX-loaded/MSN-PLGA. An increase in the percentage of drug encapsulation efficiency from 81% to 85% in CHX loaded/MSN and 92% to 95% in CHX loaded/MSN-PLGA proportionately increased with increasing the amount of CHX during the fabrication of nanoparticles. For both time-periods (24 h or 30 Days), the relative microbial viability significantly decreased by increasing the CHX content (P<0.001). Generally, the cell viability percentage of DPSCs exposed to MSN-PLGA/Blank, CHX-loaded/MSN, and CHX-loaded/MSN-PLGA, respectively was >80% indicating low cytotoxicity profiles of experimental nanoparticles. After 9 months in artificial saliva (pH 7.4), significantly highest micro-tensile bond strength value was recorded for 25:50 CHX/MSN and 25:50:50 CHX/MSN-PLGA. A homogenous and widely distributed 50:50:50 CHX-loaded/MSN-PLGA nanoparticles exhibited excellent bonding with the application of commercially available dentin adhesive.Conclusions: A pH sensitive CHX release response was noted when loaded in MSN grafted PLGA nanoparticles. The formulated drug loaded nanocarrier demonstrated excellent physicochemical, spectral, and biological characteristics. Showing considerable capacity to penetrate effectively inside dentinal tubules and having high antibacterial efficacy, this system could be potentially used in adhesive and restorative dentistry.

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In Vitro Evaluation of pH Responsive Doxazosin Loaded Mesoporous Silica Nanoparticles: A Smart Approach in Drug Delivery

Current Drug Delivery ◽

10.2174/1567201812666150722123704 ◽

2016 ◽

Vol 13 (4) ◽

pp. 574-581 ◽

Cited By ~ 3

Author(s):

Arijit Guha ◽

Nikhil Biswas ◽

Kaustav Bhattacharjee ◽

Piu Das ◽

Ketousetuo Kuotsu

Keyword(s):

Drug Delivery ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Ph Responsive ◽

In Vitro Evaluation

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Formulation of pH-sensitive chlorhexidine-loaded/mesoporous silica nanoparticles modified experimental dentin adhesive

Materials Science and Engineering C ◽

10.1016/j.msec.2021.111894 ◽

2021 ◽

Vol 122 ◽

pp. 111894 ◽

Cited By ~ 1

Author(s):

Zohaib Akram ◽

Umer Daood ◽

Sultan Aati ◽

Hein Ngo ◽

Amr S. Fawzy

Keyword(s):

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Ph Sensitive ◽

Dentin Adhesive

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Mesoporous Silica Nanoparticles and Mesoporous Bioactive Glasses for Wound Management: From Skin Regeneration to Cancer Therapy

Materials ◽

10.3390/ma14123337 ◽

2021 ◽

Vol 14 (12) ◽

pp. 3337

Author(s):

Sara Hooshmand ◽

Sahar Mollazadeh ◽

Negar Akrami ◽

Mehrnoosh Ghanad ◽

Ahmed El-Fiqi ◽

...

Keyword(s):

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Skin Regeneration ◽

Bioactive Molecules ◽

Wound Management ◽

Bioactive Glasses ◽

Wide Range

Exploring new therapies for managing skin wounds is under progress and, in this regard, mesoporous silica nanoparticles (MSNs) and mesoporous bioactive glasses (MBGs) offer great opportunities in treating acute, chronic, and malignant wounds. In general, therapeutic effectiveness of both MSNs and MBGs in different formulations (fine powder, fibers, composites etc.) has been proved over all the four stages of normal wound healing including hemostasis, inflammation, proliferation, and remodeling. The main merits of these porous substances can be summarized as their excellent biocompatibility and the ability of loading and delivering a wide range of both hydrophobic and hydrophilic bioactive molecules and chemicals. In addition, doping with inorganic elements (e.g., Cu, Ga, and Ta) into MSNs and MBGs structure is a feasible and practical approach to prepare customized materials for improved skin regeneration. Nowadays, MSNs and MBGs could be utilized in the concept of targeted therapy of skin malignancies (e.g., melanoma) by grafting of specific ligands. Since potential effects of various parameters including the chemical composition, particle size/morphology, textural properties, and surface chemistry should be comprehensively determined via cellular in vitro and in vivo assays, it seems still too early to draw a conclusion on ultimate efficacy of MSNs and MBGs in skin regeneration. In this regard, there are some concerns over the final fate of MSNs and MBGs in the wound site plus optimal dosages for achieving the best outcomes that deserve careful investigation in the future.

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Antimicrobial and antibiofilm activities of meropenem loaded-mesoporous silica nanoparticles against carbapenem-resistant Pseudomonas aeruginosa

Journal of Biomaterials Applications ◽

10.1177/08853282211003848 ◽

2021 ◽

pp. 088532822110038

Author(s):

Mohammad Yousef Memar ◽

Mina Yekani ◽

Hadi Ghanbari ◽

Edris Nabizadeh ◽

Sepideh Zununi Vahed ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Carbapenem Resistant ◽

Toxicity In Vitro ◽

Different Levels

The aims of the present study were the determination of antimicrobial and antibiofilm effects of meropenem-loaded mesoporous silica nanoparticles (MSNs) on carbapenem resistant Pseudomonas aeruginosa ( P. aeruginosa) and cytotoxicity properties in vitro. The meropenem-loaded MSNs had shown antibacterial and biofilm inhibitory activities on all isolates at different levels lower than MICs and BICs of meropenem. The viability of HC-04 cells treated with serial concentrations as MICs and BICs of meropenem-loaded MSNs was 92–100%. According to the obtained results, meropenem-loaded MSNs display the significant antibacterial and antibiofilm effects against carbapenem resistant and biofilm forming P. aeruginosa and low cell toxicity in vitro. Then, the prepared system can be an appropriate option for the delivery of carbapenem for further evaluation in vivo assays.

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Polymeric Mesoporous Silica Nanoparticles for Enhanced Delivery of 5-Fluorouracil In Vitro

Pharmaceutics ◽

10.3390/pharmaceutics11060288 ◽

2019 ◽

Vol 11 (6) ◽

pp. 288 ◽

Cited By ~ 19

Author(s):

Thashini Moodley ◽

Moganavelli Singh

Keyword(s):

Side Effects ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Therapeutic Potential ◽

Mesoporous Silica Nanoparticles ◽

Drug Loading ◽

Hek293 Cells ◽

Cancer Drug ◽

Delivery Vehicles

There is a need for the improvement of conventional cancer treatment strategies by incorporation of targeted and non-invasive procedures aimed to reduce side-effects, drug resistance, and recurrent metastases. The anti-cancer drug, 5-fluorouracil (5-FU), is linked to a variety of induced-systemic toxicities due to its lack of specificity and potent administration regimens, necessitating the development of delivery vehicles that can enhance its therapeutic potential, while minimizing associated side-effects. Polymeric mesoporous silica nanoparticles (MSNs) have gained popularity as delivery vehicles due to their high loading capacities, biocompatibility, and good pharmacokinetics. MSNs produced in this study were functionalized with the biocompatible polymers, chitosan, and poly(ethylene)glycol to produce monodisperse NPs of 36–65 nm, with a large surface area of 710.36 m2/g, large pore volume, diameter spanning 9.8 nm, and a favorable zeta potential allowing for stability and enhanced uptake of 5-FU. Significant drug loading (0.15–0.18 mg5FU/mgmsn), controlled release profiles (15–65%) over 72 hours, and cell specific cytotoxicity in cancer cells (Caco-2, MCF-7, and HeLa) with reduced cell viability (≥50%) over the non-cancer (HEK293) cells were established. Overall, these 5FU-MSN formulations have been shown to be safe and effective delivery systems in vitro, with potential for in vivo applications.

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