Safety Assessment of Nano-Hydroxyapatite as an Oral Care Ingredient according to the EU Cosmetics Regulation

Hydroxyapatite nanoparticles (HAP-NP) are incorporated in oral care products such as toothpastes and mouthwashes to treat dental sensitivity or to promote enamel remineralisation. Despite the good performance of HAP-NP in this application, it is important to ensure its safety for consumers. For that reason, the Scientific Committee on Consumer Safety (SCCS) evaluated the safety of HAP-NP as an oral care ingredient, but the issued opinion was not completely conclusive and the SCCS recommended that additional tests should be performed. Here, we used a commercially available human gingival epithelium (HGE) as a non-animal alternative and MTT cell viability, LDH activity, and IL-1alpha production were evaluated after 3.1% HAP-NP treatment for 10 min, 1 h, and 3 h. Moreover, the absorption of HAP-NP in the gingival tissue was assessed by transmission electron microscopy (TEM) analysis. Finally, the dissolution behaviour of HAP-NP in simulated gastric fluid was also investigated. No deleterious effect was observed for HGE tissues incubated with HAP-NP for all time-points and parameters evaluated. Moreover, a complete dissolution of 3.1% HAP-NP in simulated gastric fluid was observed after 7.5 min at 37 °C. In conclusion, our results evidence the safety of HAP-NP for oral care products with the use of an in vitro replacement alternative for human gingival epithelium and a simulated gastric fluid assay.

Download Full-text

Formulation of Quaternized Aminated Chitosan Nanoparticles for Efficient Encapsulation and Slow Release of Curcumin

Molecules ◽

10.3390/molecules26020449 ◽

2021 ◽

Vol 26 (2) ◽

pp. 449

Author(s):

Ahmed M. Omer ◽

Zyta M. Ziora ◽

Tamer M. Tamer ◽

Randa E. Khalifa ◽

Mohamed A. Hassan ◽

...

Keyword(s):

Slow Release ◽

Sodium Tripolyphosphate ◽

Chitosan Nanoparticles ◽

Gastric Fluid ◽

Release Profile ◽

Simulated Gastric Fluid ◽

Maximum Value ◽

Structure Surface ◽

Drug Encapsulation Efficiency

An effective drug nanocarrier was developed on the basis of a quaternized aminated chitosan (Q-AmCs) derivative for the efficient encapsulation and slow release of the curcumin (Cur)-drug. A simple ionic gelation method was conducted to formulate Q-AmCs nanoparticles (NPs), using different ratios of sodium tripolyphosphate (TPP) as an ionic crosslinker. Various characterization tools were employed to investigate the structure, surface morphology, and thermal properties of the formulated nanoparticles. The formulated Q-AmCs NPs displayed a smaller particle size of 162 ± 9.10 nm, and higher surface positive charges, with a maximum potential of +48.3 mV, compared to native aminated chitosan (AmCs) NPs (231 ± 7.14 nm, +32.8 mV). The Cur-drug encapsulation efficiency was greatly improved and reached a maximum value of 94.4 ± 0.91%, compared to 75.0 ± 1.13% for AmCs NPs. Moreover, the in vitro Cur-release profile was investigated under the conditions of simulated gastric fluid [SGF; pH 1.2] and simulated colon fluid [SCF; pH 7.4]. For Q-AmCs NPs, the Cur-release rate was meaningfully decreased, and recorded a cumulative release value of 54.0% at pH 7.4, compared to 73.0% for AmCs NPs. The formulated nanoparticles exhibited acceptable biocompatibility and biodegradability. These findings emphasize that Q-AmCs NPs have an outstanding potential for the delivery and slow release of anticancer drugs.

Download Full-text

THE USE OF CLINOPTILOLITES AS CARRIER OF METFORMIN HYDROCHLORIDE IN DRUG DELIVERY SYSTEM: IN VITRO DRUG RELEASE STUDY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i11.24366 ◽

2018 ◽

Vol 11 (11) ◽

pp. 285

Author(s):

Putra Imwa ◽

Kusumawati Igaw

Keyword(s):

Drug Release ◽

Gastric Fluid ◽

Simulated Gastric Fluid ◽

Metformin Hydrochloride ◽

Simulated Intestinal Fluid ◽

In Vitro Drug Release ◽

Encapsulation Process ◽

N2 Sorption ◽

Metformin Hcl

Objective: As an antidiabetic drug, metformin hydrochloride (HCl) has been well known to possess low oral bioavailability and short half-life. In this study, we prepared the drug delivery system (DDS) of metformin HCl and clinoptilolite as its carrier. The in vitro drug release profile was further investigated.Methods: DDS was made by encapsulating metformin HCl on clinoptilolite using the wet impregnation method at various pH and initial concentration of metformin HCl. Fourier transform infrared spectrometer (FTIR), X-ray diffractometer (XRD), and N2 Sorption Analyzer were used to characterize the as-synthesized DDS. Drug release study was conducted by stirring the DDS in simulated gastric fluid and simulated intestinal fluid over 12 h.Results: The encapsulation process was achieved optimally at pH 7.0 and initial concentration of metformin HCl of 300 mg/l (CLI2-300 denoted DDS). The results of FTIR and N2 sorption analyzer confirmed the existence of metformin HCl on clinoptilolites. Meanwhile, the XRD result showed that the crystallinity of clinoptilolites remained unchanged after the encapsulation process. The cumulative drug release in the simulated gastric fluid was found to be higher than that in the simulated intestinal fluid, which indicated the potent influence of pH on the release properties of the drugs. The drug release kinetics of metformin HCl from clinoptilolite was best fitted into the Korsmeyer-Peppas model with non-Fickian transport mechanism.Conclusion: We found that clinoptilolite was suitable for DDS application, particularly as a carrier of metformin HCl.

Download Full-text

Preparation, Characterization, and In Vitro Evaluation of Resveratrol-Loaded Cellulose Aerogel

Materials ◽

10.3390/ma13071624 ◽

2020 ◽

Vol 13 (7) ◽

pp. 1624

Author(s):

Lili Qin ◽

Xinyu Zhao ◽

Yiwei He ◽

Hongqiang Wang ◽

Hanjing Wei ◽

...

Keyword(s):

High Speed ◽

Drug Carrier ◽

Phosphate Buffer Solution ◽

Gastric Fluid ◽

Simulated Gastric Fluid ◽

Oxidized Cellulose ◽

Buffer Solution ◽

Aggregation State ◽

Cellulose Aerogel

Resveratrol is a natural active ingredient found in plants, which is a polyphenolic compound and has a variety of pharmaceutical uses. Resveratrol-loaded TEMPO-oxidized cellulose aerogel (RLTA) was prepared using a freeze-drying method, employing high speed homogenization followed by rapid freezing with liquid nitrogen. RLTAs were designed at varying drug–cellulose aerogel ratios (1:2, 2:3, 3:2, and 2:1). It could be seen via scanning electron microscopy (SEM) that Res integrated into TEMPO-oxidized cellulose (TC) at different ratios, which changed its aggregation state and turned it into a short rod-like structure. Fourier transform infrared (FTIR) spectra confirmed that the RLTAs had the characteristic peaks of TC and Res. In addition, X-ray diffraction (XRD) demonstrated that the grain size of RLTA was obviously smaller than that of pure Res. RLTAs also had excellent stability in both simulated gastric fluid and phosphate buffer solution. The drug release rate was initially completed within 5 h under a loading rate of 30.7 wt%. The results of an MTT assay showed the low toxicity and good biocompatibility of the RLTAs. TC aerogel could be a promising drug carrier that may be widely used in designing and preparing novel biomedicine.

Download Full-text

Inhibition of Estrogenic Response of Yeast Screen Assay by Exposure to Non-Lethal Levels of Metallic Nanoparticles

Applied Sciences ◽

10.3390/app10113796 ◽

2020 ◽

Vol 10 (11) ◽

pp. 3796

Author(s):

Byoung-cheun Lee ◽

Cuong N. Duong ◽

Jungkon Kim ◽

Suejin Kim ◽

Ig-chun Eom ◽

...

Keyword(s):

Metallic Nanoparticles ◽

Estrogenic Activity ◽

Endocrine Disrupting Compounds ◽

Cell Organelles ◽

Yeast Saccharomyces Cerevisiae ◽

Tem Analysis ◽

Environmental Media ◽

Transmission Electron ◽

17Β Estradiol

In order to investigate the effects of metallic nanoparticles (NPs) on the performance of in vitro bioassay, zinc oxide NP (ZnO NP), aluminum oxide NP (Al2O3 NP), bare silver NP (Ag NP), and Ag NP capped with citrate (Agcit NP) were evaluated with yeast (Saccharomyces cerevisiae Y190) two-hybrid system (YES assay), carrying Japanese medaka estrogen receptors (mERs) in the presence of 17β-estradiol (E2, 10−6 M), a reference chemical for estrogenic activity. The distribution of NPs in the yeast was also examined by field-emission transmission electron microscopy (FE-TEM). The results show that TEM analysis revealed that NPs were present inside the yeast and accumulated deep inside the cell organelles, suggesting that cell death was caused by NPs. However, despite no significant change of mortality, the E2 estrogenic activities in yeast exposed to ZnO NP and Al2O3 NP were dose-dependently reduced. For Ag NP and Agcit NP, such phenomenon observed in the exposure of ZnO NP and Al2O3 NP did not occur. From the observations, we found that ZnO NP and Al2O3 NP in the environmental media could result in underestimated estrogenicity of endocrine-disrupting compounds when evaluated by YES assay.

Download Full-text

The Antioxidant Properties of Pectin Fractions Isolated from Vegetables Using a Simulated Gastric Fluid

Journal of Chemistry ◽

10.1155/2017/5898594 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Vasily V. Smirnov ◽

Victoria V. Golovchenko ◽

Fedor V. Vityazev ◽

Olga A. Patova ◽

Nikolay Yu. Selivanov ◽

...

Keyword(s):

Xanthine Oxidase ◽

Antioxidant Properties ◽

Sweet Pepper ◽

Structural Features ◽

Gastric Fluid ◽

Simulated Gastric Fluid ◽

Oxygen Species ◽

Pectic Polysaccharides ◽

White Cabbage

The antioxidant properties of vegetable pectin fractions against intraluminal reactive oxygen species were elucidated in vitro in conjunction with their structural features. The pectin fractions were isolated using a simulated gastric fluid (pH 1.5, pepsin 0.5 g/L, 37°C, 4 h) from fresh white cabbage, carrot, onion, and sweet pepper. The fraction from onion was found to inhibit the production of superoxide radicals by inhibiting the xanthine oxidase. The high molecular weight of onion pectin and a large number of galactose residues in its side chains appeared to participate in interaction with xanthine oxidase. All the isolated pectic polysaccharides were found to be associated with protein (2–9%) and phenolics (0.5–0.7%) as contaminants; these contaminants were shown to be responsible for the antioxidant effect of vegetable pectin fractions against the hydroxyl and 1,1-diphenyl-2-picrylhydrazyl radicals.

Download Full-text

Stability of recombinant 2 S albumin allergens in vitro

Biochemical Society Transactions ◽

10.1042/bst0300913 ◽

2002 ◽

Vol 30 (6) ◽

pp. 913-915 ◽

Cited By ~ 14

Author(s):

G. J. Murtagh ◽

M. Dumoulin ◽

D. B. Archer ◽

M. J. Alcocer

Keyword(s):

Immune Response ◽

Circulatory System ◽

Gastric Fluid ◽

Low Ph ◽

Simulated Gastric Fluid ◽

Brazil Nut

Two well known 2 S albumins, Ber e 1 from brazil nut and sunflower 2 S albumin 8 (SFA-8), have been expressed in a eukaryotic system and purified. Analysis of recombinant versions of Ber e 1 and SFA-8 revealed them to be significantly more resistant to digestion by pepsin than BSA, and to be stable for up to 30 min in simulated gastric fluid. Unfolding monitored by CD indicated that both proteins were also very resistant to denaturation induced by heat and low pH. These results suggest that, although the ability of 2 S albumins to reach the circulatory system may be a prerequisite for the allergenicity of this group of proteins, stability is just one of a number of characteristics that provoke a selective immune response.

Download Full-text

In Vitro Evaluation of Eudragit Matrices for Oral Delivery of BCG Vaccine to Animals

10.20944/preprints201904.0062.v1 ◽

2019 ◽

Author(s):

Imran Saleem ◽

Allan Coombes ◽

Mark Chambers

Keyword(s):

Oral Delivery ◽

Freeze Drying ◽

Tween 80 ◽

Gastric Fluid ◽

Powder Compaction ◽

Bcg Vaccine ◽

Simulated Gastric Fluid ◽

Physical Damage ◽

Freeze Dried

Bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally but oral delivery is highly advantageous for immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in PBS, containing Tween 80, with and without the addition of mannitol or trehalose. Samples were frozen at -20oC, freeze-dried and the lyophilised powders were compressed to produce BCG-Eudragit matrices. Production of the dried powders resulted in a reduction in BCG viability. Substantial losses in viability occurred at the initial formulation stage and at the stage of powder compaction. Data indicated that the Eudragit matrix protected BCG against simulated gastric fluid (SGF). The matrices remained intact in SGF and dissolved completely in SIF within three hours. The inclusion of mannitol or trehalose in the matrix provided additional protection to BCG during freeze-drying. Control needs to be exercised over BCG aggregation, freeze-drying and powder compaction conditions to minimise physical damage of the bacterial cell wall and maximise the viability of oral BCG vaccines prepared by dry powder compaction.

Download Full-text

Preparation and characterization of baicalein loaded phytosomes: Assessment of in vitro parameters

International Journal of PharmTech Research ◽

10.20902/jptr.2019.120404 ◽

2020 ◽

Vol 12 (4) ◽

pp. 22-29

Author(s):

KanchanV Zade ◽

Alok Pal Jain

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Differential Scanning Calorimetry ◽

Herbal Extracts ◽

Scanning Calorimetry ◽

Reverse Phase ◽

Tem Analysis ◽

Transmission Electron

Phytosome is a complex between natural active ingredient and a phospholipid. Further, phytosomes been applied to many popular herbal extracts or active molecules for augmenting oral dissolution. Therefore, in present investigation, orally administered Baicalein, atype of flavanoids, is poorly absorbed, and shows suboptimal dissolution. The phytosomes encapsulating baicalein (1:1 Mm) were prepared by reverse phase evaporation method followed by lyophilization. Transmission electron microscopy (TEM) analysis revealed that phytosomes were almost spherical in shape with particle size below 100 nm. The Powder ex-ray diffraction (PXRD) and differential scanning calorimetry (DSC) demonstrated that Baicalein loaded phytosomes were amorphous in nature. Amorphization of therapeutic moiety leads to improvement in dissolution. In conclusion, epigallocatechin loaded phytosomes exhibited promising results and warrant further in vitro andin vivo investigations under a set of stringent parameters for transforming in to a clinically viable products.

Download Full-text

Gastrin and Nitric Oxide Production in Cultured Gastric Antral Mucosa Are Altered in Response to a Gastric Digest of a Dietary Supplement

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.684203 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jennifer L. MacNicol ◽

Wendy Pearson

Keyword(s):

Nitric Oxide ◽

Cell Viability ◽

Dietary Supplement ◽

Culture Media ◽

Gastric Fluid ◽

Simulated Gastric Fluid ◽

Antral Mucosa ◽

The Impact

In vitro organ culture can provide insight into isolated mucosal responses to particular environmental stimuli. The objective of the present study was to investigate the impact of a prolonged culturing time as well as the addition of acidic gastric fluid into the in vitro environment of cultured gastric antral tissue to evaluate how altering the commonly used neutral environment impacted tissue. Furthermore, we aimed to investigate the impact of G's Formula, a dietary supplement for horses, on the secretion of gastrin, interleukin1-beta (IL-1β), and nitric oxide (NO). These biomarkers are of interest due to their effects on gastric motility and mucosal activity. Gastric mucosal tissue explants from porcine stomachs were cultured in the presence of a simulated gastric fluid (BL, n = 14), simulated gastric fluid containing the dietary supplement G's Formula (DF, n = 12), or an equal volume of phosphate buffered saline (CO, n = 14). At 48 and 60 h, 10−5 M carbachol was used to stimulate gastrin secretion. Cell viability was assessed at 72 h using calcein and ethidium-homodimer 1 staining. Media was analyzed for gastrin, IL-1β, and NO at 48, 60, and 72 h. There were no effects of treatment or carbachol stimulation on explant cell viability. Carbachol resulted in a significant increase in gastrin concentration in CO and DF treatments, but not in BL. NO was higher in CO than in BL, and NO increased in the CO and DF treatments but not in BL. In conclusion, the addition of carbachol and gastric digests to culture media did not impact cell viability. The use of an acidic gastric digest (BL) reduced the effect of cholinergic stimulation with carbachol at a concentration of 10−5 M and reduced NO secretion. The addition of the dietary supplement to the gastric digest (DF) appeared to mediate these effects within this model. Further research is required to evaluate the specific effects of this dietary supplement on direct markers of mucosal activity and the functional relevance of these results in vivo.

Download Full-text

IN VITRO RELEASE STUDIES OF CARBAMAZEPINE TABLETS AND BENZOYL METRONIDAZOLE SUSPENSIONS USING THE FLOW-THROUGH CELL APPARATUS AND SIMULATED GASTROINTESTINAL FLUIDS

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2017v9i4.18929 ◽

2017 ◽

Vol 9 (4) ◽

pp. 54 ◽

Cited By ~ 3

Author(s):

Jose Raul Medina ◽

Jonathan Hernandez ◽

Marcela Hurtado

Keyword(s):

In Vitro Release ◽

Gastric Fluid ◽

Simulated Gastric Fluid ◽

Dissolution Time ◽

Intestinal Fluid ◽

Simulated Intestinal Fluid ◽

Release Studies ◽

Flow Through ◽

Vitro Release

Objective: To characterize the in vitro release of carbamazepine tablets and benzoyl metronidazole suspensions using the flow-through cell apparatus and simulated gastrointestinal fluids.Methods: Tegretol® tablets, Flagyl® suspension, and generic formulations of each were tested. Release studies were performed using an automated flow-through cell apparatus. Simulated gastric fluid (with and without pepsin) and simulated intestinal fluid (without pancreatin) at 16 ml/min and fasted state simulated intestinal fluid at 8 ml/min, all at 37.0±0.5 °C, were used as dissolution media. The quantity of dissolved carbamazepine and benzoyl metronidazole was determined at 5-min intervals until 60 min at 285 and 278 nm, respectively. Percentage dissolved at 60 min, mean dissolution time, dissolution efficiency values, and t10%, t25%, t50% and t63.2% were calculated. Mean values for all parameters were compared between the reference and generic formulations using Studentʼs t-test. Dissolution data were fitted to different kinetic models.Results: Simulated gastric fluid without pepsin showed no discriminative capability for carbamazepine tablets. Significant differences were observed between the reference and generic formulations for almost all parameters (*P<0.05). In some cases, the logistic model best described the in vitro release of both drugs.Conclusion: Using an apparatus and media that best simulates the gastrointestinal environment, we identified differences in the rate and extent of dissolution of both drugs that could help to optimise the design of interchangeable formulations. Based on the physicochemical characteristics of carbamazepine and benzoyl metronidazole and the conditions in which the formulations were tested, these differences could be of clinical relevance.

Download Full-text