Coated particles and their uses

Abstract

Provided are coated particles and methods of their use for providing healthcare benefits. More specifically, the present invention provides amino acid and/or polymer-coated particles, or particles coated with other materials, for binding to, or otherwise associating with, surfaces of the oral cavity.

Claims

1. A coated micro/nano-particle comprising: (a) a substrate consisting of microparticles or nanoparticles made from poly(lactic-co-glycolic acid) (“PLGA”) and (b) a coating covalently bonded to the substrate comprising one or more materials selected from the group consisting of ethyl lauroyl arginate HCl, ##STR00030##

2. The coated micro/nano-particle of claim 1, wherein the coating comprises the Compound 17, the Compound 18 or the Compound 31.

3. The coated micro/nano-particle according to claim 1 further comprising an active ingredient.

4. A method of providing a benefit to the oral cavity comprising introducing to said oral cavity a coated-micro/nano-particle according to claim 1.

5. A method of providing a benefit to the oral cavity comprising introducing to said oral cavity a coated micro/nano-particle according to claim 3.

6. A method of measuring adherence of a coated micro/nano-particle according to claim 1 to a hydroxyapatite surface comprising providing saliva-coated hydroxyapatite particles (HAP) and the coated micro/nano-particles, mixing said saliva-coated HAP and the coated micro/nano-coated particles and incubating the mixture, washing the resulting HAP to remove loose coated micro/nano-particles and collecting the eluent, to determine how much coated micro/nano-particle is sticking to the saliva coated HAP and how much has eluted off.

Description

EXAMPLES

Example 1

(1) Applicants have made several coated particles in accord with the Surface Conjugation procedure of present invention as described herein. As shown in Tables 1-2, applicants have coated PLGA particles with Leucine, Valine, Tryptophan, Methionine, and Arginine with Chitosan and Xanthan gum, with polyvinyl pyrrolidone (Plasdone K29/32), ethyl lauroyl arginate HCl (LAE and with several compounds of Formula I. Such coated particles were then assayed in accord with the Fluorescent PLGA Particle Binding Assay Procedure described herein and the results shown in the Tables 1 and 2 below.

(2) TABLE-US-00001 TABLE 1 CONTROL LAE HLA HMP PSSA elute 1 44004 53131 51145 46139 45424 elute 2 44258 55917 55056 47294 46104 wash 1 44989 54437 48126 46326 46941 wash 2 19323 19844 29424 16783 22667 wash 3  6163  9800 12342  6276  7785 wash 4  4102  6124  8299  3732  3111

(3) TABLE-US-00002 TABLE 2 Cont. Trypto- Methi- Argi- Chito- Xanthan H20 HLA 17 18 31 Leucine Valine phan onine nine K29 san Iron Gum 1 2 3 4 5 6 7 8 9 10 11 12 13 14 elute 1 40179 40940 46331 45981 470777  44022 43637 42969 43874 43544 42235 41487 37783 38275 elute 2 41602 39325 44069 not elute not elute 43775 39421 41819 42047 43597 42833 44100 not elute 40309 wash 1 33717 40128 40072 not elute not elute 36404 37812 38450 38765 42145 38568 42579 not elute 42501 wash 2 10541 20092 1670 not elute not elute 15709 19342 17180 15714 17362 15563 32460 not elute 35681 wash 3 3023 8046 5902 50511 51951 5150 4276 4255 3525 4069 4930 26204 42823 6160 wash 4 1490 4353 3129 33023 36129 2540 2594 2047 1858 2129 2494 19569 26957 24156 wash 5 1329 2945 1734 19396 17702 1612 1795 1338 1292 1448 1519 12608  9313 33728

(4) The results in the tables show the degree of for each polymer-coated PLGA particle with the saliva coated HAP. The polymers that generated a very strong binding were chitosan and xanthan gum. The strong binders were LAE, HLA, and compounds 17, 18, and 31. The medium binders were all the amino acids and PVP. The weak binder was PSSA and the molecules that exhibited no interaction were iron and HMP.

Example 2

(5) Applicants have made and tested several coated particles in accord with the Fluorescent PLGA Particle Adsorption Assay of present invention as described herein using the materials as shown in the tables. As shown in the Tables applicants have coated particles with Distearmonium/Diethonium Chloride PG Dimethicone (Silquat J2 4B), chitosan (Chitosan LMW), polyquaternium-10 (Ucare JR 30 M, Ucare LR-400), myristamidopropyl PG-dimonium chloride phosphate (Arlaskil PTM-LQ-AP), Dimethicone PEG-8 Phosphate (Siliphos A-100), and methyl methacrylate (MMA) and diethylaminoethyl methacrylate (DEAEMA) (Kollicoat Smart Seal 30D).

(6) Calculation:

(7) The raw data from the fluorescent reader was used for calculation. The mean of readings of total fluorescence of each technology was calculated to obtain average total fluorescence. The data from collected eluents and washes was normalized using average total fluorescence of respective resuspended PLGA particles and technology. This was calculated for each sample well for all washes treated with various technologies. The formula used for normalization is:
(Raw data point of fluorescence of eluent from wash of a technology sample well/Average total fluorescence of that technology)*100
The average and standard deviation was calculated for each wash step of respective technology. The graph plotted shows normalized fluorescence per technology with error bars showing standard of deviation of normalized data.

(8) TABLE-US-00003 TABLE 3 1% 0.25% 0.25% 0.25% Ariasilk Kollicoat Silquat Chitosan Ucare Ucare PTM- Siliphos Smart Seal JR-4B Water LMW JR 30 M LR 400 LQ-AP A 100 30D Total 1 4603 4255 4664 2405 3535 4647 4357 7020 florescence 2 4936 4746 5116 4789 3281 4877 4547 7662 Average 4769.5 4500.5 4890 3597 3408 4762 4452 7341

(9) TABLE-US-00004 TABLE 4 1% 0.25% 0.25% 0.25% Arlasilk Kollicoat Silquat Chitosin Ucare Ucare PTM- Siliphos Smart Seal JR-4B Water LMW JR 30 M LR 400 LQ-AP A 100 30D Raw Treatment 1251 2523 2855 8 90 943 3231 29 data elute 1277 2498 2876 8 87 1002 3293 35 1303 2676 2928 5 38 1049 2974 30 Wash 1 363 1513 1724 4 217 654 1893 5 364 1551 1888 4 203 496 1819 5 361 1562 2055 3 93 531 1856 6 Wash 2 61 181 176 4 118 170 216 3 49 154 210 1 127 55 130 3 47 143 156 2 68 195 101 2 Wash 3 43 114 128 2 93 88 32 1 30 145 83 3 81 32 29 2 32 147 83 3 29 67 27 1

(10) TABLE-US-00005 TABLE 5 Total Fluorescence 1% 0.5% 0.25% 0.25% 0.125% 0.25% 0.125% Kollicoat Kollicoat Kollicoat 1% 0.5% 0.25% Ucare Ucare Ucare Ucare smartseal smartseal smartseal PQ6 PQ6 PQ6 LR400 LR400 Water JR 400 JR 400 30 D 30 D 30 D 1 3258 3617 3837 3967 2966 3805 2091 3850 6352 8996 7048 2 3653 3545 3867 4072 3047 3885 2217 3829 6502 8339 7140 avg 3455.5 3581 3852 4019.5 3006.5 3845 2154 3839.5 6427 8667.5 7094

(11) TABLE-US-00006 TABLE 6 Raw Data 1% 0.5% 0.25% 0.25% 0.125% 0.25% 0.125% Kollicoat Kollicoat Kollicoat 1% 0.5% 0.25% Ucare Ucare Ucare Ucare smartseal smartseal smartseal PQ6 PQ6 PQ6 LR400 LR400 Water JR 400 JR 400 30 D 30 D 30 D Waste 1688 1411 1308 866 200 2680 260 1315 4 4 23 1699 1266 1123 748 272 2515 420 1357 3 3 19 1748 1128 1183 757 345 2663 372 1334 3 6 19 Wash 1 844 652 768 1111 58 1495 101 1543 2 2 10 901 889 910 1211 62 1403 153 1718 2 1 21 918 808 953 1063 81 1521 130 1536 3 2 21 Wash 2 163 199 287 430 3 102 2 263 1 2 9 155 214 346 481 4 147 2 323 2 1 6 135 245 354 509 3 126 2 416 1 1 10 Wash 3 56 83 129 284 3 38 2 174 1 1 5 56 111 199 329 3 41 1 180 2 2 4 67 121 172 344 4 43 1 211 2 1 9

(12) The results show the degree of affinity for each technology-coated PLGA particle with the saliva coated HAP. The polymers that generated very strong to strong binding (0-10% and 10-25% fluorescence in wash elutes) were polyquaternium 10 (such as UCare LR 400, UCare JR 30, UCare JR 400), co-polymer consisting of co-polymer comprising methyl methacrylate (MMA) and diethylaminoethyl methacrylate (DEAEMA) (such as Kollicoat Smart seal 30 D). The polymers that generated medium binding (25-40% fluorescence in wash elutes) are polyquaternium 6 (such as Tilamar Quat 640), Myristamidopropyl PG-Dimonium Chloride Phosphate (such as Arlasilk PTM), silicones (such as Distearmonium/Diethonium Chloride PG Dimethicone, Silquat J2 4B). The molecules that showed weak binding to no binding (40%<fluorescence in wash elutes) are water, chitosan with low molecular weight, anionic molecules (such as Siliphos A 100).

(13) Retention Calculation: The percentage of retention was calculated by assuming total percentage to be 100%. The percent normalized elutes from treatment and washes where then subtracted from 100% of total fluorescence to measure degree of affinity (percent of retention) for each technology-coated PLGA particle with saliva coated HAP.

(14) The results show the degree of affinity for each technology-coated PLGA particle with saliva coated HAP. The polymers that showed very strong to strong retention were (90-100% and 75-90%) were polyquaternium 10 (such as UCare LR 400, UCare JR 30, UCare JR 400), co-polymer consisting of co-polymer comprising methyl methacrylate (MMA) and diethylaminoethyl methacrylate (DEAEMA) (such as Kollicoat Smart seal 30 D). The polymers that generated medium binding (60-75%) are polyquaternium 6 (such as Tilamar Quat 640), Myristamidopropyl PG-Dimonium Chloride Phosphate (such as Arlasilk PTM), silicones (such as Distearmonium/Diethonium Chloride PG Dimethicone, Silquat J2 4B). The molecules that showed weak binding to no binding (40-60% and 40%>) are water, chitosan with low molecular weight, anionic molecules (such as Siliphos A 100). This interaction is also shown in the photographs of the respective wells as indicated by the intensity of yellow-green color.