Synthesis of amidic alginate derivatives and their application in microencapsulation of λ-cyhalothrin

1-Octyl amine was covalently coupled to sodium alginate(NaAlg) in an aqueous-phase reaction via acidamide functions using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC-HCl) as a coupling reagent to provide octyl-grafted amphiphilic alginate-amide derivative(OAAD) for subsequent use in λ-cyhalothrin (LCH) microcapsule application. The structure of OAAD was confirmed by FT-IR and (1)H NMR spectroscopies. The new alginate-amide derivative was used for fabricating microcapsule that can effectively encapsulate LCH by emulsification-gelation technique. The microcapsules were characterized by optical microscopy (OM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and laser particle size analysis. The encapsulation efficiency and drug release behavior of LCH from the microcapsules were investigated. Results showed that the microcapsules were in spherical form with diameter mostly in the range of 0.5-10 μm and possessed a structure with LCH as core and OAAD as shell. The encapsulation efficiency and the release performance of the microcapsules were influenced by DS of OAAD and amount of CaCl(2). The mechanism of LCH release was found to vary from anomalous to Fickian to quasi-Fickian transport with the DS of OAAD varied from 10.8 to 30.3 and the CaCl(2)/emulsion ratios varied from 0.09 to 0.03%.     

Development of a peptide-containing chewing gum as a sustained release antiplaque antimicrobial delivery system

The objective of this study was to characterize the stability of KSL-W, an antimicrobial decapeptide shown to inhibit the growth of oral bacterial strains associated with caries development and plaque formation, and its potential as an antiplaque agent in a chewing gum formulation. KSL-W formulations with or without the commercial antibacterial agent cetylpyridinium chloride (CPC) were prepared. The release of KSL-W from the gums was assessed in vitro using a chewing gum apparatus and in vivo by a chew-out method. A reverse-phase high-performance liquid chromatography method was developed for assaying KSL-W. Raw material stability and temperature and pH effects on the stability of KSL-W solutions and interactions of KSL-W with tooth-like material, hydroxyapatite discs, were investigated. KSL-W was most stable in acidic aqueous solutions and underwent rapid hydrolysis in base. It was stable to enzymatic degradation in human saliva for 1 hour but was degraded by pancreatic serine proteases. KSL-W readily adsorbed to hydroxyapatite, suggesting that it will also adsorb to the teeth when delivered to the oral cavity. The inclusion of CPC caused a large increase in the rate and extent of KSL-W released from the gums. The gum formulations displayed promising in vitro/ in vivo release profiles, wherein as much as 90% of the KSL-W was released in a sustained manner within 30 minutes in vivo. These results suggest that KSL-W possesses the stability, adsorption, and release characteristics necessary for local delivery to the oral cavity in a chewing gum formulation, there-by serving as a novel antiplaque agent. Published: March 30, 2007     

Process optimization for microencapsulation of probiotic yeasts

Background

Microencapsulation is a technique which improves the survival and viability of probiotics. We demonstrate encapsulation of five potential probiotic yeasts with alginate and gum as encapsulation matrices to improve their gastrointestinal transit.

Methods

Gum extracted from various cereals viz. rice, oats, barley, finger millet and pearl millet along with alginate have been used to encapsulate five potential probiotic yeasts. Screening was carried out by measuring swelling index, encapsulation efficiency and nutritional value of microcapsules encapsulated with alginate and gum. The concentration of OBG, sodium alginate and inoculum dosage of probiotic yeasts was optimized using response surface methodology (RSM). Efficiency of alginate OBG microcapsules with or without coating materials viz. whey protein and chitosan also tested. The mucoadhesion ability and storage stability of alginate OBG microcapsules with coating materials were tested.

Results

Highest encapsulation efficiency of probiotic yeasts was noted using oats bran gum (OBG) microcapsules along with alginate in all the five probiotic yeasts. Notably whey protein coated microcapsules showed maximum GIT tolerance (95%) and mucoadhesion (90%) for L. starkeyi VIT-MN03. The minimum loss of viability was observed in L. starkeyi VITMN03 microcapsules on 60th day of storage.

Conclusions

This is the first report on optimization and survival of microencapsulated probiotic yeasts under simulated GIT conditions using natural gum and alginate as encapsulation matrices and whey protein as coating material.

     

Preparation of a water-in-oil-in-water (W/O/W) type microcapsules by a single-droplet-drying method and change in encapsulation efficiency of a hydrophilic substance during storage

Microcapsules of a water-in-oil-in-water (W/O/W) emulsion, which contained a hydrophilic substance, 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt (PTSA), in its inner aqueous phase, was prepared by hot-air-drying or freeze-drying the emulsion using a single-droplet-drying method. Pullulan, maltodextrin, or gum arabic was used as a wall material, and the oily phase was tricaprylin, oleic acid, olive oil, or a mixture of tricaprylin and olive oil. An encapsulation efficiency higher than 0.95 was reached except for the microcapsules prepared using gum arabic and oleic acid. The hot-air-dried microcapsules were generally more stable than the freeze-dried microcapsules at 37 degrees C and various relative humidities. The stability was higher for the microcapsules with tricaprylin as the oily phase than for the microcapsules with oleic acid. The higher stability of the microcapsules with tricaprylin would be ascribed to the lower partition coefficient of PTSA to the oily phase. There was a tendency for the stability to be higher at lower relative humidity for both the hot-air- and freeze-dried microcapsules. The volumetric fraction of olive oil in its mixture with tricaprylin did not significantly affect either the encapsulation efficiency or the stability of the hot-air-dried microcapsules.     

Preparation of a Water-in-oil-in-water (W/O/W) Type Microcapsules by a Single-droplet-drying Method and Change in Encapsulation Efficiency of a Hydrophilic Substance during Storage

Microcapsules of a water-in-oil-in-water (W/O/W) emulsion, which contained a hydrophilic substance, 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt (PTSA), in its inner aqueous phase, was prepared by hot-air-drying or freeze-drying the emulsion using a single-droplet-drying method. Pullulan, maltodextrin, or gum arabic was used as a wall material, and the oily phase was tricaprylin, oleic acid, olive oil, or a mixture of tricaprylin and olive oil. An encapsulation efficiency higher than 0.95 was reached except for the microcapsules prepared using gum arabic and oleic acid. The hot-air-dried microcapsules were generally more stable than the freeze-dried microcapsules at 37°C and various relative humidities. The stability was higher for the microcapsules with tricaprylin as the oily phase than for the microcapsules with oleic acid. The higher stability of the microcapsules with tricaprylin would be ascribed to the lower partition coefficient of PTSA to the oily phase. There was a tendency for the stability to be higher at lower relative humidity for both the hot-air- and freeze-dried microcapsules. The volumetric fraction of olive oil in its mixture with tricaprylin did not significantly affect either the encapsulation efficiency or the stability of the hot-air-dried microcapsules.     

The development of a simple objective test of mastication suitable for older people,using chewing gums

Aims: To develop and assess a simple test for evaluating the mastication of visco‐elastic foods and prosthodontic success subsequent to treatment of older people. Method: The weight lost from chewing gum during mastication tests and the saliva secreted is weighed. The percentage of the original gum weight that is chewed out in a defined number of strokes is termed the Masticatory Effectiveness (ME) Material: Five edentate and three dentate volunteers were selected to provide a range of dental states and age. Four commercially available chewing gums of different origins and perceived hardness were tested, one without sweetener acted as a control for salivary stimulation. Intervention: Pre‐weighed samples of each gum were chewed, each for defined numbers of strokes. The saliva secreted was collected and weighed. The chewed gum was desiccated and the total weight loss of sweeteners chewed out provided an objective measure of chewing performance. Results: Weight loss showed large differences between gums, between subjects and the number of strokes. ME was significantly correlated with salivary secretion rates for two subjects. The interaction between subject and gum was statistically significant, established by an ANOVA model, the value of which is shown for multivariate studies. Differential success between gums of different thickness may provide evaluation of denture stability. Conclusions: Measuring the weight lost from gums during chewing provides a simple test of masticatory effectiveness of visco‐elastic foods. This has particular value both in functional assessment of older people and in physiological research.     

Encapsulation of basic fibroblast growth factor by polyelectrolyte multilayer microcapsules and its controlled release for enhancing cell proliferation

Basic fibroblast growth factor (FGF2) is an important protein for cellular activity and highly vulnerable to environmental conditions. FGF2 protected by heparin and bovine serum albumin was loaded into the microcapsules by a coprecipitation-based layer-by-layer encapsulation method. Low cytotoxic and biodegradable polyelectrolytes dextran sulfate and poly-L-arginine were used for capsule shell assembly. The shell thickness-dependent encapsulation efficiency was measured by enzyme-linked immunosorbent assay. A maximum encapsulation efficiency of 42% could be achieved by microcapsules with a shell thickness of 14 layers. The effects of microcapsule concentration and shell thickness on cytotoxicity, FGF2 release kinetics, and L929 cell proliferation were evaluated in vitro. The advantage of using microcapsules as the carrier for FGF2 controlled release for enhancing L929 cell proliferation was analyzed.     

Use of hydrophilic natural gums in formulation of sustained-release matrix tablets of tramadol hydrochloride

The objective of this work was to develop matrix sustained-release tablets of highly water-soluble tramadol HCl using natural gums (xanthan [X gum] and guar [G gum]) as cost-effective, nontoxic, easily available, and suitable hydrophilic matrix systems compared with the extensively investigated hydrophilic matrices (ie, hydroxypropyl methylcellulose [HPMC]/carboxymethyl cellulose [CMC] with respect to in vitro drug release rate) and hydration rate of the polymers. Matrix tablets of tramadol (dose 100 mg) were produced by direct compression method. Different ratios, of 100∶0, 80∶20, 60∶40, 20∶80, 0∶100 of G gum (or X):HPMC, X gum:G gum, and triple mixture of these polymers (G gum, X gum, HPMC) were applied. After evaluation of physical characteristics of tablets, the dissolution test was, performed in the phosphate buffer media (pH 7.4) up to 8 hours. Tablets with only X had the highest mean dissolution time (MDT), the least dissolution efficiency (DE₈%), and released the drug following a zero-order model via swelling, diffusion, and erosion mechanisms. Guar gum alone could not efficiently control the drug release, while X and all combinations of natural gums with HPMC could retard tramadol HCl release. However, according to the similarity factor (f ₂), pure HPMC and H₈G₂ were the most similar formulations to Topalgic-LP as the reference standard. Published: March 17, 2006     

Quantification and Qualification of Bacteria Trapped in Chewed Gum

Chewing of gum contributes to the maintenance of oral health. Many oral diseases, including caries and periodontal disease, are caused by bacteria. However, it is unknown whether chewing of gum can remove bacteria from the oral cavity. Here, we hypothesize that chewing of gum can trap bacteria and remove them from the oral cavity. To test this hypothesis, we developed two methods to quantify numbers of bacteria trapped in chewed gum. In the first method, known numbers of bacteria were finger-chewed into gum and chewed gums were molded to standard dimensions, sonicated and plated to determine numbers of colony-forming-units incorporated, yielding calibration curves of colony-forming-units retrieved versus finger-chewed in. In a second method, calibration curves were created by finger-chewing known numbers of bacteria into gum and subsequently dissolving the gum in a mixture of chloroform and tris-ethylenediaminetetraacetic-acid (TE)-buffer. The TE-buffer was analyzed using quantitative Polymerase-Chain-Reaction (qPCR), yielding calibration curves of total numbers of bacteria versus finger-chewed in. Next, five volunteers were requested to chew gum up to 10 min after which numbers of colony-forming-units and total numbers of bacteria trapped in chewed gum were determined using the above methods. The qPCR method, involving both dead and live bacteria yielded higher numbers of retrieved bacteria than plating, involving only viable bacteria. Numbers of trapped bacteria were maximal during initial chewing after which a slow decrease over time up to 10 min was observed. Around 10⁸ bacteria were detected per gum piece depending on the method and gum considered. The number of species trapped in chewed gum increased with chewing time. Trapped bacteria were clearly visualized in chewed gum using scanning-electron-microscopy. Summarizing, using novel methods to quantify and qualify oral bacteria trapped in chewed gum, the hypothesis is confirmed that chewing of gum can trap and remove bacteria from the oral cavity.     

Effect of nicotine chewing gum on smoking behaviour and as an aid to cigarette withdrawal.

In a double-blind, placebo-controlled, crossover trial the effect of 2-mg nicotine chewing gum was studied in 43 smokers when they were smoking as inclined and when they were trying to stop smoking. Although 70% of the smokers stopped smoking during treatment, only 23% were still abstinent after one year. The effect of the nicotine, though significant, was small compared with the overall reduction in smoking. When the subjects were smoking as inclined cigarette consumption was reduced by an average of 37% on the nicotine gum compared with 31% on placebo gum, while avergage carboxyhaemoglobin (COHb) levels were reduced by 26% and 15% on the active and placebo gums respectively. When subjects tried to stop smoking there was a further considerable reduction in cigarette consumption, but no longer any difference between the two gums. Nevertheless, average COHb was still lower on the active gum. Plasma nicotine levels on the nicotine gum averaged only 10-7 ng/ml compared with 27-4 ng/ml after smoking. Better results could be expected with 4-mg nicotine gums.     

Preparation and in vitro evaluation of polystyrene-coated diltiazem-resin complex by oil-in-water emulsion solvent evaporation method

The purpose of this study was to examine the suitability of polystyrene-coated (PS-coated) microcapsules of drug-resin complex for achieving prolonged release of diltiazem-HCl, a highly water-soluble drug, in simulated gastric and intestinal fluid. The drug was bound to Indion 254, a cation-exchange resin, and the resulting resinate was microencapsulated with PS using an oil-in-water emulsion-solvent evaporation method. The effect of various formulation parameters on the characteristics of the microcapsules was studied. Mean diameter and encapsulation efficiency of the microcapsules rose with an increase in the concentration of emulsion stabilizer and the coat/core ratio, while the same characteristics tended to decrease with an increase in the volume of the organic disperse phase. The desorption of drug from the uncoated resinate was quite rapid and independent of the pH of the dissolution media. On the other hand, the drug release from the microcapsules was prolonged for different periods of time depending on the formulation parameters and was also found to be independent of the pH of the dissolution media. Both the encapsulation efficiency and the retardation of drug release were found to be dependent on the uniformity of coating, which in turn was influenced by the formulation parameters. Kinetic studies revealed that the desorption of drug from the resinate obeyed the typical particle diffusion process, whereas the drug release from the microencapsulated resinate followed the diffusion-controlled model in accordance with the Higuchi equation. PS appeared to be a suitable polymer to provide prolonged release of diltiazem independent of the pH of the dissolution media.     

Development,Optimization, and Anti-diabetic Activity of Gliclazide-Loaded Alginate–Methyl Cellulose Mucoadhesive Microcapsules

The purpose of this work was to develop and optimize gliclazide-loaded alginate–methyl cellulose mucoadhesive microcapsules by ionotropic gelation using central composite design. The effect of formulation parameters like polymer blend ratio and cross-linker (CaCl₂) concentration on properties of gliclazide-loaded alginate–methyl cellulose microcapsules like drug encapsulation efficiency and drug release were optimized. The optimized microcapsules were subjected to swelling, mucoadhesive, and in vivo studies. The observed responses coincided well with the predicted values from the optimization technique. The optimized microcapsules showed high drug encapsulation efficiency (83.57 ± 2.59% to 85.52 ± 3.07%) with low T _50% (time for 50% drug release, 5.68 ± 0.09 to 5.83 ± 0.11 h). The in vitro drug release pattern from optimized microcapsules was found to be controlled-release pattern (zero order) with case II transport release mechanism. Particle sizes of these optimized microcapsules were 0.767 ± 0.085 to 0.937 ± 0.086 mm. These microcapsules also exhibited good mucoadhesive properties. The in vivo studies on alloxan-induced diabetic rats indicated the significant hypoglycemic effect that was observed 12 h after oral administration of optimized mucoadhesive microcapsules. The developed and optimized alginate–methyl cellulose microcapsules are suitable for prolonged systemic absorption of gliclazide to maintain lower blood glucose level and improved patient compliance.     

Encapsulation performance of layer-by-layer microcapsules for proteins

This study reports on the encapsulation efficiency of proteins in dextran sulfate/poly-L-arginine-based microcapsules, fabricated via layer-by-layer assembly (LbL). For this purpose, radiolabeled proteins are entrapped in CaCO(3) microparticles, followed by LbL coating of the CaCO(3) cores and subsequent dissolving of the CaCO(3) using EDTA. To allow to improve protein encapsulation in LbL microcapsules, we studied all steps in the preparation of the microcapsules where loss of protein load might occur. The encapsulation efficiency of proteins in LbL microcapsules turns out to be strongly dependent on both the charge and molecular weight of the protein as well as on the number of polyelectrolyte bilayers the microcapsules consist of.     

Cross-linked guar gum microspheres: A viable approach for improved delivery of anticancer drugs for the treatment of colorectal cancer

In the present work, guar gum microspheres containing methotrexate (MTX) were prepared and characterized for local release of drug in the colon, which is a prerequisite for the effective treatment of colorectal cancer. Guar gum microspheres were prepared by the emulsification method using glutaraldehyde as a cross-linking agent. Surface morphological characteristics were investigated using scanning electron microscopy. Particle size, shape, and surface morphology were significantly affected by guar gum concentration, glutaral dehyde concentration, emulsifier concentration (Span 80), stirring rate, stirring time, and operating temperature. MTX-loaded microspheres demonstrated high entrapment efficiency (75.7%). The in vitro drug release was investigated using a US Pharmacopeia paddle type (type II) dissolution rate test apparatus in different media (phosphate-buffered saline [PBS], gastrointestinal fluid of different pH, and rat cecal content release medium), which was found to be affected by a change to the guar gum concentration and glutaraldehyde concentration. The drug release in PBS (pH 7.4) and simulated gastric fluids followed a similar pattern and had a similar release rate, while a significant increase in percent cumulative drug release (91.0%) was observed in the medium containing rat cecal content. In in vivo studies, guar gum microspheres delivered most of their drug load (79.0%) to the colon, whereas plain drug suspensions could deliver only 23% of their total dose to the target site. Guar gum microspheres showed adequate potential in achieving local release of drug in in vitro release studies, and this finding was further endorsed with in vivo studies. Published: September 8, 2006     

Chitosan microcapsules loaded with either miconazole nitrate or clotrimazole,prepared via emulsion technique

In this paper, a simple and versatile coacervation technique has been developed by using an ultrasound-assisted oil/water emulsion method for the preparation of antifungal agent-loaded microcapsules. Two types of chitosan microcapsules are successfully prepared. The mean particle size of the chitosan/miconazole nitrate microcapsules is 2.6 μm and that of the chitosan/clotrimazole microcapsules is 4.1 μm. The encapsulation efficiency of the chitosan/miconazole nitrate microcapsules (77.58–96.81%) is relatively higher than that of the chitosan/clotrimazole microcapsules (56.66–93.82%). The in vitro drug release performance of the microcapsules shows that the chitosan/miconazole nitrate microcapsules release about 49.5% of the drug while chitosan/clotrimazole microcapsules release more than 66.1% of the drug after 12 h under a pressure of 5 kg at pH 5.5, which is similar to the pH of human skin. The prepared drug-loaded microcapsules could be applied onto bandages or socks, and will continuously release antifungal drugs in a controlled manner under pressure.     

Sorbitol Gum in Xerostomics: The Effects on Dental Plaque pH and Salivary Flow Rates1

Adequate salivary flow is important for patient comfort and maintenance of oral health. Xerostomia, or dry mouth, is a common clinical complaint. Masticatory and gustatory activity can stimulate salivary flow from functional salivary tissue and the use of sugarless mints and gums have been recommended to individuals who complain of xerostomia, but there are minimum clinical data. A clinical study assessing the effect on salivary flow rates and dental plaque pH of a sorbitol-sweetened chewing gum in subjects with the complaint of xerostomia was conducted. The chewing of the gum in this present study stimulated salivary flow in the subjects with xerostomia. Statistically significant stimulated whole mouth and parotid salivary flow rate increases were found when compared to unstimulated whole mouth and parotid salivary flow rates. Chewing of the sorbitol-sweetened gum also effectively reduced the drop in pH seen following the exposure to a fermentable carbohydrate. The findings of this present study indicate that chewing of a sorbitol-sweetened gum may be of benefit to patients with the complaint of xerostomia.     

Poly(acrylonitrile) grafted Ipomoea seed-gums: a renewable reservoir to industrial gums

Plants of Ipomoea genus are widely distributed in India as wild vegetation and are reported source for the seed gums. Seed gums from Ipomoea dasysperma, Ipomoea hederacea, and Ipomoea palmata plants were grafted with polyacrylonitrile (PAN) using potassium persulfate/ascorbic acid redox initiator for modifying their properties for potential industrial applications. Under identical grafting conditions, the extent of the grafting was observed to be dependent on the galactose-to-mannose ratio and the degree of the branching in the galactomannans. Viscosity, gel formation, film formation, and the shelf life of the grafted gum solutions and water and saline retention capacity of the grafted seed gums were determined and compared with the parent gums. Water retention of the alkalie hydrolyzed grafted seed gums were also studied. Grafted gums were characterized using FTIR, NMR, and XRD analysis.     

Microencapsulation of β-Carotene Based on Casein/Guar Gum Blend Using Zeta Potential-Yield Stress Phenomenon: an Approach to Enhance Photo-stability and Retention of Functionality

β-Carotene, abundant majorly in carrot, pink guava yams, spinach, kale, sweet potato, and palm oil, is an important nutrient for human health due to its scavenging action upon reactive free radicals wherever produced in the body. Inclusion of liposoluble β-carotene in foods and food ingredients is a challenging aspect due to its labile nature and low absorption from natural sources. This fact has led to the application of encapsulation of β-carotene to improve stability and bioavailability. The present work was aimed to fabricate microcapsules (MCs) of β-carotene oily dispersion using the complex coacervation technique with casein (CA) and guar gum (GG) blend. The ratio of CA:GG was found to be 1:0.5 (w/v) when optimized on the basis of zeta potential-yield stress phenomenon. These possessed a higher percentage yield (71.34 ± 0.55%), lower particle size (176.47 ± 4.65 μm), higher encapsulation efficiency (65.95 ± 5.33%), and in general, a uniform surface morphology was observed with particles showing optimized release behavior. Prepared MCs manifested effective and controlled release (up to 98%) following zero-order kinetics which was adequately explained by the Korseymer-Peppas model. The stability of the freeze-dried MCs was established in simulated gastrointestinal fluids (SGF, SIF) for 8 h. Antioxidant activity of the MCs was studied and revealed the retention of the functional architecture of β-carotene in freeze-dried MCs. Minimal photolytic degradation upon encapsulation of β-carotene addressed the challenge regarding photo-stability of β-carotene as confirmed via mass spectroscopy.     

Yeast Cell Microcapsules as a Novel Carrier for Cholecalciferol Encapsulation: Development,Characterization and Release Properties

In this study Saccharomyces cerevisiae yeast cells was used as a novel vehicle for encapsulation of vitamin D₃. The effects of initial cholecalciferol concentration (100,000 and 500,000 IU/g yeast), yeast cell pretreatment (plasmolysis with NaCl) and drying method (spray or freeze drying) on microcapsules properties were investigated. It was found that the vitamin concentration and drying method had significant influence on encapsulation efficiency (EE) and size of yeast microcapsules. Furthermore, EE values were more increased by the plasmolysis treatment. The highest EE was obtained for plasmolysed and spray dried yeast cells prepared using initial cholecalciferol concentration of 2.5 mg per gram of yeast cells (76.10?±?6.92%). The values of mean particle size were 3.43–7.91 μm. The presence of cholecalciferol in yeast microcapsules was confirmed by X-ray diffraction (XRD) and Fourier transform-infrared (FT-IR) analyses. The in vitro cholecalciferol release from yeast microcapsules in phosphate buffer saline solution (PBS) followed a controlled release manner consistent with a Fickian diffusion mechanism. In addition, the release studies in simulated gastrointestinal tract showed sustained release of cholecalciferol in the stomach condition and significant release in intestinal medium.     

PYCNOGENOL chewing gum minimizes gingival bleeding and plaque formation.

PYCNOGENOL is an antioxidant phytochemical shown to have antiinflammatory activity in both the in vitro and in vivo models. This study compared the effects of chewing gums with and without PYCNOGENOL on gingival bleeding and plaque formation in 40 human subjects. In this double-blind study, subjects were assigned randomly to receive either control gums without PYCNOGENOL or experimental gums containng 5 mg PYCNOGENOL. Subjects used chewing gums for 14 days. Gingival bleeding and plaque scores were taken before and after the experiment. PYCNOGENOL chewing gums significantly reduced gingival bleeding, while no changes were noted in bleeding indexes in control subjects who used regular chewing gums. Subjects using regular control gums had significant increases of dental plaque accumulation during the two-week period. No increases in plaque accumulation were noted in subjects using PYCNOGENOL chewing gums. The data of this study suggest that the use of Pycnogenol chewing gums can minimize gingival bleeding and plaque accumulation.