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

Author(s):  
Zohaib Akram ◽  
Sultan Aati ◽  
Hein Ngo ◽  
Amr Fawzy

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.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zohaib Akram ◽  
Sultan Aati ◽  
Hein Ngo ◽  
Amr Fawzy

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.


2021 ◽  
Author(s):  
Zohaib Akram ◽  
Sultan Aati ◽  
Hein Ngo ◽  
Amr Fawzy

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.


Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3337
Author(s):  
Sara Hooshmand ◽  
Sahar Mollazadeh ◽  
Negar Akrami ◽  
Mehrnoosh Ghanad ◽  
Ahmed El-Fiqi ◽  
...  

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.


2021 ◽  
pp. 088532822110038
Author(s):  
Mohammad Yousef Memar ◽  
Mina Yekani ◽  
Hadi Ghanbari ◽  
Edris Nabizadeh ◽  
Sepideh Zununi Vahed ◽  
...  

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.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 288 ◽  
Author(s):  
Thashini Moodley ◽  
Moganavelli Singh

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.


2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Diti Desai ◽  
Didem Sen Karaman ◽  
Neeraj Prabhakar ◽  
Sina Tadayon ◽  
Alain Duchanoy ◽  
...  

AbstractMesoporous silica nanoparticles (MSNs) have advanced to the forefront of multifunctional nanoparticulate systems in nanomedicine, owing to this highly fexible materials platform enabling a multitude of design options, often in a modular fashion. Drug delivery ability, detectability via diferent imaging modalities, and stimuliresponsiveness are often combined into one particle system. Very sophisticated and versatile designs along with impressive demonstrations of applicability have been reported to date, but a common ground when it comes to some critical considerations valid for any nanoparticle intended for biomedical purposes is lacking to some degree. In this study, we attempt to take a glance at some of the most crucial aspects of biomedical nanoparticulate design and relate how they apply specifically toMSNs. These considerations include fuorophore labeling and leaching with respect to immobilization to MSNs, the surrounding conditions, carrier biodegradability, and surface coating. Surface modifcation strategies and surface charge tuning are further considered in conjunction to the relative amount of cellular uptake and serum protein adsorption. Cellular internalization routes and biological techniques used to evaluate especially in vitro biobehavior are discussed. Our attempt is hereby to draw attention to some of the most frequently occurring issues to be considered in the design of MSN systems for biomedical applications


Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 460
Author(s):  
Minja Mladenović ◽  
Ibrahim Morgan ◽  
Nebojša Ilić ◽  
Mohamad Saoud ◽  
Marija V. Pergal ◽  
...  

Ruthenium complexes are attracting interest in cancer treatment due to their potent cytotoxic activity. However, as their high toxicity may also affect healthy tissues, efficient and selective drug delivery systems to tumour tissues are needed. Our study focuses on the construction of such drug delivery systems for the delivery of cytotoxic Ru(II) complexes upon exposure to a weakly acidic environment of tumours. As nanocarriers, mesoporous silica nanoparticles (MSN) are utilized, whose surface is functionalized with two types of ligands, (2-thienylmethyl)hydrazine hydrochloride (H1) and (5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)hydrazine (H2), which were attached to MSN through a pH-responsive hydrazone linkage. Further coordination to ruthenium(II) center yielded two types of nanomaterials MSN-H1[Ru] and MSN-H2[Ru]. Spectrophotometric measurements of the drug release kinetics at different pH (5.0, 6.0 and 7.4) confirm the enhanced release of Ru(II) complexes at lower pH values, which is further supported by inductively coupled plasma optical emission spectrometry (ICP-OES) measurements. Furthermore, the cytotoxicity effect of the released metallotherapeutics is evaluated in vitro on metastatic B16F1 melanoma cells and enhanced cancer cell-killing efficacy is demonstrated upon exposure of the nanomaterials to weakly acidic conditions. The obtained results showcase the promising capabilities of the designed MSN nanocarriers for the pH-responsive delivery of metallotherapeutics and targeted treatment of cancer.


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