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Fulltext Formulation design and optimization of triclosan loaded nanoparticles for enhanced drug delivery across gingival sulcus by resolution IV modeling of design expert

Nafiu Aminu, Chan, Siok-Yee, Toh, Seok-Ming

Journal of Biomedical and Clinical Sciences, 2018;3(1):83-90.
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The aim of this study was to design and systematically optimize
triclosan loaded nanoparticles (TCS-loaded NPs) formulation for the treatment
of periodontal disease. Triclosan (TCS) is a broad spectrum antimicrobial
agent that has been used in the treatment of the disease. The free drug has
poor aqueous solubility and therefore may encounter permeability problems
when applied to the oral cavity. Resolution IV model of Design-Expert®
software (version 10) was used for the design of experiment and optimization
of TCS-loaded NPs. The nanoparticles (NPs) were prepared using the solvent
displacement method. Effect of factors that were investigated include drugpolymer ratio, surfactant concentration, stirring speed, stirring duration, and
drug-polymer injection rate. Particle size, zeta potential, polydispersity index
(PDI) and entrapment efficiency (EE) were the critical quality attributes
selected for the study. Desirability function determined by the software for
optimized TCS-loaded NPs was 0.704. The observed particle size, PDI, zeta
potential and EE of the optimized TCS-loaded NPs was found to be 135 ± 2.3
nm, 0.1 ± 0.012, -30 ± -4 mV and 75 ± 6%, respectively. It was found that
particle size increases by elevating the concentration of polymer and
decreases with an increase in surfactant concentration and stirring speed.
Zeta potential was found to increase when surfactant concentration was
reduced. Both surfactant concentration and drug to polymer ratio were found
to negatively affect PDI while % EE was positively influenced by the increase
in polymer concentration and decrease in surfactant concentration. The use of
Design-Expert®
software helped in identifying suitable levels of critical quality
parameters for preparing improved NPs formulation for delivery of TCS into
the periodontal pocket.
A dual-action chitosan-based nanogel system of triclosan and flurbiprofen for localised treatment of periodontitis

Aminu N, Chan SY, Yam MF, Toh SM

Int J Pharm, 2019 Oct 30;570:118659.
PMID: 31493495 DOI: 10.1016/j.ijpharm.2019.118659

This study aimed to develop a dual action, namely anti-inflammatory and antimicrobial, nanogels (NG) for the treatment of periodontitis using triclosan (TCS) and flurbiprofen (FLB). Triclosan, an antimicrobial drug, was prepared as nanoparticles (NPs) using poly-ε-caprolactone (PCL), while flurbiprofen, an anti-inflammatory drug, was directly loaded in a chitosan (CS) based hydrogel. The entwinement of both NPs and hydrogel loaded systems resulted in the NG. The characterisation data confirmed that the developed formulation consists of nanosized spherical structures and displays pH-dependent swelling/erosion and temperature-responsiveness. Besides, the NG exhibited adequate bioadhesiveness using the chicken pouch model and displayed antibacterial activity through the agar plate method. An in-vivo study of the NG on experimental periodontitis (EP) rats confirmed the dual antibacterial and anti-inflammatory effects which revealed an excellent therapeutic outcome. In conclusion, a dual action NG was successfully developed and proved to have superior therapeutic effects in comparison to physical mixtures of the individual drugs.
The improved dissolution performance of a post processing treated spray-dried crystalline solid dispersion of poorly soluble drugs

Chan SY, Toh SM, Khan NH, Chung YY, Cheah XZ

Drug Dev Ind Pharm, 2016 Nov;42(11):1800-1812.
PMID: 27049232

Solution-mediated transformation has been cited as one of the main problems that deteriorate dissolution performances of solid dispersion (SD). This is mainly attributed by the recrystallization tendency of poorly soluble drug. Eventually, it will lead to extensive agglomeration which is a key process in reducing the dissolution performance of SD and offsets the true benefit of SD system. Here, a post-processing treatment is suggested in order to reduce the recrystallization tendency and hence bring forth the dissolution advantage of SD system.
Fulltext The evaluation of healing effect of triclosan and flurbiprofen-loaded nanogels in experimental periodontitis in rats by morphometric analysis

Aminu N, Yam MF, Chan SY, Bello I, Umar NM, Nuhu T, et al.

Saudi Dent J, 2021 Nov;33(7):554-559.
PMID: 34803300 DOI: 10.1016/j.sdentj.2020.08.008

Purpose: To evaluate therapeutic effectiveness of antibacterial triclosan (TCS) and anti-inflammatory flurbiprofen (FLB)-loaded nanogels system in ligature-induced experimental periodontitis in rats.
Methodology: A total of 72 Sprague-Dawley rats were used in this study. Four groups (n = 18 each) were randomly created: Group 1 - neither subjected to experimental periodontitis nor to any treatment; Group 2 - subjected to experimental periodontitis but not treated; Group 3 - subjected to experimental periodontitis and then treated with the developed nanogels; Group 4 - subjected to experimental periodontitis and then placed on a mixture of pure TCS and FLB treatment. The experimental periodontitis was induced on the lower incisors by applying a ligature which was kept for 14 days. Treatment was done for 7 days, and sampling was done at 7, 14, and 28 day of the post-induction experimental period. Morphometric analysis was conducted to assess the clinical outcomes and healing effect.
Results: The morphometric findings showed that the group treated with the developed TCS and FLB-loaded nanogels recovered better and faster than a mixture of pure TCS and FLB. At 28 day of the experimental period, there was no significant difference (p > 0.05) between the baseline control group and the nanogels treated group.
Conclusions: The developed TCS and FLB-loaded nanogels was found to be effective in the treatment of experimental periodontitis in rats. The used experimental periodontitis model was found to be simple and easily reproducible.