Method of making nanocapsules and use thereof

Abstract

A nanocapsule includes a core comprising a monomer; a shell comprising a polyurethane; and a catalyst for the monomer in the core and / or shell. A self-healing dental composition may include a plurality of the nanocapsules; at least one photocurable monomer; at least one photoinitiator; at least one filler; and at least one pigment to substantially match or mimic a tooth color.

Description

[0001] METHOD OF MAKING NANOCAPSULES AND USE THEREOF

[0002] This PCT international application claims priority to US Serial No. 63 / 755,636, which was filed on 7 February 2025 in the U.S. Patent and Trademark Office, the entirety of which is incorporated herein by reference.

[0003] FIELD OF INVENTION

[0004] The present invention is directed to a method of making nanocapsules, to the nanocapsules, and to a self-healing dental composition. The self-healing dental composition may be used for dental restoration.

[0005] SUMMARY OF INVENTION

[0006] The invention provides in a first embodiment a nanocapsule comprising a core comprising a monomer and a shell comprising polyurethane. A catalyst for the monomer in the core may be present in or chemically incorporated into the core and / or shell.

[0007] The invention provides in a second embodiment further to any of the previous embodiments a nanocapsule wherein the monomer in the core comprises a dimethacrylate.

[0008] The invention provides in a third embodiment further to any of the previous embodiments a nanocapsule wherein the monomer in the core comprises

[0009] 1 ,6-hexanediol dimethacrylate.

[0010] The invention provides in a fourth embodiment further to any of the previous embodiments a nanocapsule wherein the polyurethane comprises a polyol having hydroxyl groups that react with isocyanate groups of isophorone diisocyanate. The polyol may be glycerol.The invention provides in a fifth embodiment further to any of the previous embodiments a nanocapsule wherein the catalyst for the monomer comprises a tertiary amine.

[0011] The invention provides in a sixth embodiment further to any of the previous embodiments a nanocapsule wherein the catalyst for the monomer comprises n,n-bis(2-hydroxyethyl)-p-toluidine.

[0012] The invention provides in a seventh embodiment further to any of the previous embodiments a nanocapsule having a catalyst for forming the polyurethane.

[0013] The invention provides in an eighth embodiment further to any of the previous embodiments a nanocapsule having a diameter of about 100-1000 nm.

[0014] The invention provides a first self-healing dental composition which, according to a first embodiment, comprises a plurality of nanocapsules according to any of the previous embodiments; at least one photocurable monomer; at least one photoinitiator; at least one filler; and at least one pigment to substantially match or mimic a tooth color.

[0015] The invention provides a self-healing dental composition in a second embodiment further to any of the previous embodiments a dental composition wherein the at least one photocurable monomer comprises triethylene glycol dimethacrylate, bisphenol-A-glycidyl methacrylate, or any combination thereof.

[0016] The invention provides a self-healing dental composition in a third embodiment further to any of the previous embodiments a dental composition wherein the at least one photoinitiator comprises camphorquinone, ethyl-4-dimethylaminobenzoate, or any combination thereof.The invention provides a self-healing dental composition in a fourth embodiment further to any of the previous embodiments a dental composition wherein the at least one filler comprises silanated barium borosilicate glass.

[0017] The invention provides a self-healing dental composition in a fifth embodiment further to any of the previous embodiments a dental composition wherein the at least one pigment comprises at least one of titanium dioxide, zinc oxide, cerium oxide, yttrium oxide, or any combination thereof.

[0018] The invention provides a self-healing dental composition in a sixth embodiment further to any of the previous embodiments a dental composition further comprising ytterbium (III) fluoride.

[0019] The invention provides a self-healing dental composition in a seventh embodiment further to any of the previous embodiments a dental composition further comprising benzoyl peroxide and butylated hydroxytoluene.

[0020] The invention provides in a first method embodiment a method for making nanocapsules comprising mixing a surfactant, glycerol, and water to form a first solution; adding hexadecane to the first solution; adding a mixture of a monomer, a tertiary amine catalyst for the monomer, and isophorone diisocyanate, to the first solution to form a second solution; sonicating the second solution; adding a catalyst for the glycerol and the isophorone diisocyanate to the sonicated second solution to polymerize and form polyurethane; and forming a plurality of nanoparticles.

[0021] The invention provides in a second method embodiment further to any of the previous method embodiments a method wherein the surfactant comprises sodium dodecyl sulfate.The invention provides in a third method embodiment further to any of the previous method embodiments a method wherein the tertiary amine catalyst comprises n,n-bis(2-hydroxyethyl)-p-toluidine.

[0022] The invention provides in a fourth method embodiment further to any of the previous method embodiments a method wherein the monomer comprises a dimethacrylate.

[0023] The invention provides in a fifth method embodiment further to any of the previous method embodiments a method wherein the monomer comprises 1 ,6-hexanediol methacrylate.

[0024] The invention provides in a sixth method embodiment further to any of the previous method embodiments a method wherein the catalyst for the glycerol and isocyanate comprises dibutyltin dilaurate.

[0025] The invention provides in a seventh method embodiment a method for making nanocapsules comprising providing a substantially continuous flow of the components to make the nanocapsule further to any one of the previous embodiments to a microfluidic device and reacting the components substantially simultaneously to make a plurality of nanocapsules.

[0026] BRIEF DESCRIPTION OF THE DRAWING

[0027] FIG. 1 is a schematic diagram of a method for forming nanocapsules according to an embodiment of the present invention.

[0028] FIG. 2 is a schematic diagram of a method for forming nanocapsules according to another embodiment of the present invention.

[0029] FIG. 3A is a picture showing microfracture formation and fatigue striations in a control dental composition without nanocapsules during flexural fatigue testing.FIG. 3B is a picture showing the self-healing dental composition according to an embodiment of the present invention during flexural fatigue testing with release of monomer from the nanocapsule and stopping or progression of fatigue striations.

[0030] DETAILED DESCRIPTION OF THE INVENTION

[0031] The present invention is directed to a method of making nanocapsules, to the nanocapsules, and to a self-healing dental composition. The self-healing dental composition may be used for dental restoration.

[0032] In this detailed description, references to "one embodiment", "an embodiment", or “in embodiments” mean that the feature being referred to is included in at least one embodiment of the invention. Moreover, separate references to "one embodiment", "an embodiment", or “embodiments” do not necessarily refer to the same embodiment; however, neither are such embodiments mutually exclusive, unless so stated, and except as will be readily apparent to those skilled in the art. Thus, the invention can include any variety of combinations and / or integrations of the embodiments described herein.

[0033] As used herein “substantially”, “generally”, “about”, and other words of degree are relative modifiers intended to indicate permissible variation from the characteristic so modified (e.g., ±0.1%, ±0.5%, ±1.0%, ±2%, ±5%, ±10%, ±20%). It is not intended to be limited to the absolute value or characteristic which it modifies but rather possessing more of the physical or functional characteristic than its opposite, and preferably, approaching or approximating such a physical or functional characteristic.

[0034] I. Nanocaosules

[0035] According to the present invention a nanocapsule comprises a core comprising a monomer and a shell surrounding the core. The shell comprises a polyurethane. Atertiary amine catalyst for the monomer in the core may be present in or chemically incorporated into the shell and / or core.

[0036] The monomer in the core includes a dimethacrylate. In specific embodiments, the monomer may be at least one of triethylene glycol dimethacrylate, 1 ,6-hexanediol dimethacrylate (HDDMA), dodecanediol dimethacrylate, urethane dimethacrylate, or combinations thereof. In embodiments, a nanocapsule may comprise about 5% to about 80 wt.% dimethacrylate, based on the weight of the nanocapsule.

[0037] In embodiments, the tertiary amine may be at least one of p-tolyl imino diethanol, ethyl dimethyl aminobenzoate, n,n-dimethyl p-toluidine (p-TID), triethylamine, dimethyl aniline, or mixtures thereof. In embodiments, a nanocapsule may comprise about 0.1 to about 1 wt.% of the tertiary amine, based on the weight of the nanocapsule.

[0038] The polyurethane in the shell may be formed from a polyol, for example, glycerol, polyether triols, or sorbitol that reacts with an isocyanate. In embodiments, glycerol having hydroxyl groups react with or bond to isocyanate groups of an isocyanate, for example, isophorone diisocyanate (IPDI) or hexamethylene diisocyanate. In embodiments, a nanocapsule may comprise about 10 to about 40 wt.% of polyol and about 25 to about 60 wt.% of isocyanate, based on the weight of the nanocapsule.

[0039] In embodiments, the nanocapsules may have a catalyst for the reaction forming the polyurethane. In embodiments the catalyst (e.g., dibutyltin dilaurate) may be present in a nanocapsule in an amount of about 0.5 to about 1.5 wt.%, based on the weight of the nanocapsule.

[0040] In embodiments, the nanocapsules may be functionalized with a methacrylate, for example, 2-hydroxyethyl methacrylate (HEMA). The methacrylate monomer may react with the polyurethane to become part of the shell in the final nanocapsule. In embodiments, a nanocapsule may comprise about 0.1 to about 2 wt.% of the methacrylate, based on the weight of the nanocapsule.Each nanocapsule may have a diameter of about 100-1000 nm, for example, about 300-625 nm.

[0041] In specific embodiments, a loading ratio may be 0.15g tertiary amine catalyst to 10mL monomer for a weight (g) to volume (mL) loading ratio of about 1 :67.

[0042] II. Method of Making Nanocapsules

[0043] According to an embodiment of the present invention, nanocapsules may be made by: 1 ) mixing a surfactant, glycerol, and water to form a first solution;

[0044] 2) adding hexadecane to the first solution;

[0045] 3) adding a mixture of a monomer, a tertiary amine catalyst for the monomer, and isocyanate (e.g., isophorone diisocyanate) to the first solution to form a second solution; 4) sonicating the second solution;

[0046] 5) adding a catalyst for the glycerol and isocyanate to the sonicated second solution to polymerize and form polyurethane; and

[0047] 6) forming a plurality of nanoparticles.

[0048] In another embodiment, a microfluidic method may be used in which in which a substantially continuous flow of all components for making the nanocapsules may be added to a microfluidic device and reacted substantially simultaneously or in a different order than in a method using sonification.

[0049] FIG. 1 is a schematic diagram of a method for forming nanocapsules according to an embodiment of the present invention. FIG. 2 is a schematic diagram of a method for forming nanocapsules according to another embodiment of the present invention.

[0050] In embodiments, the surfactant may be an anionic surfactant. The surfactant may be at least one of sodium dodecyl sulfate (SDS) or dioctyl sulfosuccinate. In embodiments,the amount of surfactant may be about 26% to about 28% by mass of glycerol. In specific embodiments, the molar ratio of isocyanate to glycerol may be about 2:1.

[0051] In a specific embodiment, at least one of the surfactant, catalyst for the glycerol and isocyanate, solvent (e.g., water, hexadecane), or any combination thereof may not be present in the final nanocapsules.

[0052] EXAMPLES

[0053] The following are non-limiting examples of making nanocapsules according to embodiments of the present invention.

[0054] Example 1

[0055] 1. A 250 ml beaker is placed in a 1 L 50°C water bath. To the 250 ml beaker add 0.66 g sodium dodecyl sulfate (SDS) into 75 mL of deionized H2O. Stir to mix, 400 rpm until dissolved. Then add 2.32 mg glycerol and 1.5 mL hexadecane (HD) stir at 400 rpm for 1 hr.

[0056] 2. In a separate beaker of about 25-50 mL, add 11 mL of isophorone diisocyanate (IPDI); 1.5 mL of HD; 10 mL of 1 ,6-hexanediol dimethacrylate (HDDMA); butyl hydroxy toluene (BHT, inhibitor / stabilizer); and 0.15 g of N,N-Bis(2-hydroxyethyl)-p-toluidine or p-tolyl imino diethanol (p-TID). Vortex, and once everything is dissolved, syringe the mixture dropwise into the 250 mL beaker from step 1 , which is in the 50°C water bath.

[0057] 3. Ultrasonicate the mixture at an amplitude of 64.6 urn (38% of 170 urn) and a frequency of 20kHz for 1 min.

[0058] 4. While sonicating, add 200 pL of dibutyltin dilaurate (DBTDL, catalyst) to the solution and sonicate again for 1 minute at room temperature.5. Return the beaker to the 50°C water bath, stir this solution at 1 ,000 rpm for 2 hr. then 500 rpm for 24 hr.

[0059] 6. Pour overnight mixture into centrifuge tubes, adjust volume in each tube to about 40 mL with deionized (DI) H2O. Centrifuge 10,000 rpm for 30 min.

[0060] A. Decant the supernatant into a secondary waste container and discard into the designated waste stream. Resuspend the pellet with about 30 mL DI H2O and repeat the wash step an additional 5 times. Centrifuge 10,000 rpm, 20 min. for each wash step.

[0061] B. Decant supernatant after each wash and dispose of waste into the designated waste stream. After each wash the supernatant becomes clearer. After the final wash the supernatant is clear.

[0062] 7. The pellet is reconstituted in deionized H2O to form a white milky solution. Freeze the solution at -80°C for a minimum of 2 hr. After freezing the tubes are removed from the freezer, caps removed and a Kimwipe™ is secured over the mouth of the tube with a rubber band. Tubes are placed in lyophilization flasks, attach to the lyophilizer, lyophilize at -85°C (when the temperature read out turns green the machine is ready to attach the flasks). Lyophilize 72-96 hr. at maximum vacuum. Until product is dry and fluffy.

[0063] 8. After lyophilization, the nanoparticle mixture is put through a sieve 60 mesh, 250 pm openings. Take the coarse material that remained in the sieve and freeze to -80°C and lyophilize again. Pass the newly-lyophilized material through the same sieve a second time. Combine the flow-through from the second pass with the flow-through from the first pass. Repeat the process one more time on the remaining coarse material for a total of three sieving cycles. Combine all three collected flow-through fractions and store the final nanoparticle product at -80 °C. The synthesis is now complete.Example 2

[0064] 1. A 250 mL beaker is placed in a 1 L 50°C water bath over a magnetic stir plate. To the 250 mL beaker add 0.66 g SDS into 75 mL of DI H2O. Stir with magnetic stir bar to mix at 500 rpm until dissolved. Then add 2.32 g glycerol, 0.03 hydroxyethyl methacrylate (HEMA) and 1.5 mL HD stir at 400 rpm for 1 hr.

[0065] 2. In a separate beaker (about 25-50 mL) add 11 mL IPDI and 10 mL HDDMA / BHT stir, add 0.15 g pTID and dissolve, dropwise add the contents of this beaker into the 250 mL beaker in the 50°C water bath.

[0066] 3. Ultrasonicate the mixture at 20 kHz with an amplitude at 65 pm amplitude with a 1 / 8 inch probe for 1 min.

[0067] 4. Add 200 pL of DBTDL to this solution and sonicate again for 1 min. at room temperature.

[0068] 5. Return the beaker to the 50°C water bath, stir this solution at 1 ,000 rpm for 2 hr. then 500 rpm for 24 hr.

[0069] 6. Pour overnight mixture into centrifuge tubes, adjust volume in each tube to ~40 mL with DI H2O. Centrifuge 10,000 rpm (17,880 x g) for 20 min at 4°C.

[0070] A. Decant the supernatant into a waste container and discard into the designated waste stream. Resuspend the pellet with about 30 mL DI H2O and repeat the wash step an additional 5 times. Centrifuge 10,000 rpm, 20 min for each wash step.

[0071] B. Decant supernatant after each wash and dispose of waste into the designated waste stream. After each wash the supernatant becomes clearer. After the final wash the supernatant is clear.7. The pellet is reconstituted in DI H2O to form a white milky solution. Freeze the solution at -80°C for a minimum of 2 hr. After freezing the tubes are removed from the freezer, caps removed and a Kimwipe™ is secured over the mouth of the tube with a rubber band. Tubes are placed in lyophilization flasks, attach to the lyophilizer, lyophilize at -85°C for 72-96 hr at maximum vacuum. Until product is dry and fluffy.

[0072] 8. To remove aggregates after lyophilization, the nanoparticle mixture is put through a sieve 60 mesh, 250 pm openings. Take the coarse material that remained in the sieve and freeze to -80°C and lyophilize again. Pass the newly-lyophilized material through the same sieve a second time. Combine the flow-through from the second pass with the flow-through from the first pass. Repeat the process one more time on the remaining coarse material for a total of three sieving cycles. Combine all three collected flow-through fractions and store the final nanoparticle product at -80 °C. The synthesis is now complete.

[0073] III. Dental Composition

[0074] According to the present invention, a self-healing dental composition comprises a plurality of the nanocapsules; at least one photocurable monomer; at least one photoinitiator; at least one filler; and at least one pigment to substantially match or mimic a tooth color. The self-healing dental composition may be used for dental restoration.

[0075] In specific embodiments, the at least one photocurable monomer may comprise at least one of triethylene glycol dimethacrylate, bisphenol-A-glycidyl methacrylate, or any combination thereof. The amount of the at least one photocurable monomer may be about 15 to about 40 wt.% based on the total weight of the composition.

[0076] In specific embodiments, the at least one photoinitiator may be camphorquinone, ethyl-4-dimethylaminobenzoate, or any combination thereof. The amount of the at least onephotoinitiator may be about 0.2 to about 1.5 wt.% based on the total weight of the composition.

[0077] In specific embodiments, the at least one filler may be at least one of SiO2, zirconia, silanated barium borosilicate glass, Ba-AI-B-Si glass, or any combination thereof.

[0078] The amount of the at least one filler may be about 50 to about 70 wt.% based on the total weight of the composition.

[0079] In specific embodiments, the at least one pigment may be at least one of titanium dioxide, zinc oxide, cerium oxide, yttrium oxide, or any combination thereof. The amount of the at least one pigment may be about 0.1 to 0.5 wt.% based on the total weight of the composition.

[0080] In specific embodiments, the dental composition may also comprise at least one of an agent for x-ray detection such as ytterbium (III) fluoride (YbFs), an initiator for the monomer in the nanocapsules, such as benzoyl peroxide (BPO), or a stabilizer for the initiator and / or monomer, such as butylated hydroxytoluene (BHT). In embodiments, the dental composition may comprise tert-butyl peroxybenzoate initiator.

[0081] In specific embodiments, the dental composition may be as listed in Table 1 below:

[0082]

[0083]

[0084] TABLE 1

[0085] In specific embodiments, the dental composition may have the properties listed in Table 2 below, wherein the Predicate was FILTEK® Supreme Flowable Restorative (3M®):

[0086] >

[0087] >

[0088] >

[0089] <

[0090] <

[0091]

[0092]

[0093] *ISO 4049 - Dentistry: Polymer-based restorative materials

[0094] TABLE 2

[0095] The flexural fatigue of the dental composition or composite measures the average flexural force (force required to fracture) as follows:

[0096] Determine average flexural strength (force required to fracture).

[0097] Start at 50% flexural strength then cycle ± 25%.

[0098] 12,000 cycles or until fracture. If a sample fractured before 12,000 cycles, decrease initial force by 5% flexural strength for next sample (cycle 20-70%); if sample survived, increase initial force by 5% flexural strength for next sample (cycle 30-80%). n = 15 [number of samples].

[0099] Flexural fatigue ratio limit determined by:

[0100]

[0101] Xowas the lowest stress ratio level considered in the analysis and d was the fixed stress ratio increment. To determine FR, the analysis of the data was based on the least frequent event (failures vs survivals). The negative sign was used when the analysis was based on failures; otherwise, the positive sign was used. In the equations, the lowest stress ratio level considered was designated i = 0, the next i = 1, and so on, and ni was the number of failures or survivals at the given stress ratio level.

[0102] As shown in Table 3 below, the dental composite according to the present invention had a higher flexural fatigue ratio compared to the control of Table 1.

[0103]

[0104] TABLE 3

[0105] FIG. 3A is a picture showing microfracture formation and fatigue striations in a control dental composition without nanocapsules during flexural fatigue testing.

[0106] FIG. 3B is a picture showing the self-healing dental composition according to an embodiment of the present invention during flexural fatigue testing with release of monomer from the nanocapsule and stopping or progression of fatigue striations.

[0107] INDUSTRIAL APPLICABILITY

[0108] The present invention is directed to a nanocapsule, a plurality of which may be used in a self-healing dental composition. In particular, the self-healing dental composition may be used for dental restoration.

[0109] Although the present invention has been described in terms of particular exemplary and alternative embodiments, it is not limited to those embodiments. Alternative embodiments, examples, and modifications which would still be encompassed by the invention may be made by those skilled in the art, particularly in light of the foregoing teachings.

[0110] Those skilled in the art will appreciate that various adaptations and modifications of the exemplary and alternative embodiments described above can be configured without departing from the scope and spirit of the invention. Therefore, it is to be understood that, within the scope of the appended claims, the invention may be practiced other than as specifically described herein.

Claims

WHAT IS CLAIMED IS:

1. A nanocapsule, comprising:a core comprising a monomer;a shell comprising a polyurethane; anda catalyst for the monomer in the core and / or shell.

2. A nanocapsule according to Claim 1 , wherein the monomer in the core comprises a dimethacrylate.

3. A nanocapsule according to Claim 1 , wherein the monomer in the core comprises 1 ,6-hexanediol dimethacrylate.

4. A nanocapsule according to Claim 1 , wherein the polyurethane comprises a polyol having hydroxyl groups that react with isocyanate groups of isophorone diisocyanate.

5. A nanocapsule according to Claim 1 , wherein the polyol comprises glycerol.

6. A nanocapsule according to Claim 1 , wherein the catalyst for the monomer comprises a tertiary amine.

7. A nanocapsule according to any one of Claims 1 -6, wherein the catalyst for the monomer comprises n,n-bis(2-hydroxyethyl)-p-toluidine.

8. A nanocapsule according to any one of Claims 1 -6, having a catalyst for forming the polyurethane.

9. A nanocapsule according to any one of Claims 1-6, wherein the nanocapsule is functionalized with 2-hydroxyethyl methacrylate.

10. A nanocapsule according to any one of Claims 1 -6, having a diameter of about 100-1000 nm.

11. A nanocapsule according to any one of Claims 1 -6, having a diameter of about SOO-625 nm.

12. A nanocapsule according to any one of Claims 1 -6, comprising:about 5 to about 80 wt.% dimethacrylate;about 0.1 to about 1 wt.% tertiary amine;about 0.1 to about 2 wt.% 2-hydroxyethyl methacrylate;about 10 to about 40 wt.% glycerol; andabout 25 to about 60 wt.% isocyanate;13. A self-healing dental composition, comprising:a plurality of nanocapsules according to any one of Claims 1-6;at least one photocurable monomer;at least one photoinitiator;at least one filler; andat least one pigment to substantially match or mimic a tooth color.1 . A self-healing dental composition according to Claim 13, wherein the at least one photocurable monomer comprises triethylene glycol dimethacrylate, bisphenol-A-glycidyl methacrylate, or any combination thereof.

15. A self-healing dental composition according to Claim 13, wherein the at least one photoinitiator comprises camphorquinone, ethyl-4-dimethylaminobenzoate, or any combination thereof.

16. A self-healing dental composition according to Claim 13, wherein the at least one filler comprises silanated barium borosilicate glass.

17. A self-healing dental composition according to Claim 13, wherein the at least one pigment comprises at least one of titanium dioxide, zinc oxide, cerium oxide, yttrium oxide, or any combination thereof.

18. A self-healing dental composition according to Claim 13, further comprising ytterbium (III) fluoride.

19. A self-healing dental composition according to Claim 13, further comprising benzoyl peroxide and butylated hydroxytoluene.

20. A self-healing dental composition according to Claim 13, further comprising fert-butyl peroxybenzoate.

21. A self-healing dental composition according to Claim 13, wherein there is only a single kind of nanocapsule.

22. A method for making nanocapsules, comprising:mixing a surfactant, glycerol, and water to form a first solution;adding hexadecane to the first solution;adding a mixture of a monomer, a tertiary amine catalyst for the monomer, and isophorone diisocyanate, to the first solution to form a second solution;sonicating the second solution;adding a catalyst for the glycerol and the isophorone diisocyanate to the sonicated second solution to polymerize and form polyurethane; andforming a plurality of nanoparticles, each nanocapsule according to any one of Claims 1-6.

23. A method according to Claim 22, wherein the surfactant comprises sodium dodecyl sulfate.

24. A method according to Claim 22, wherein the tertiary amine catalyst comprises n,n-bis(2-hydroxyethyl)-p-toluidine.

25. A method according to Claim 22, wherein the monomer comprises a dimethacrylate.

26. A method according to Claim 22, wherein the monomer comprises 1,6-hexanediol methacrylate.

27. A method according to Claim 22, wherein the catalyst for the glycerol and isocyanate comprises dibutyltin dilaurate.

29. A method for making nanocapsules comprising:providing a substantially continuous flow of the components to make the nanocapsule of any one of Claims 1 -6 using a microfluidic device; andreacting the components substantially simultaneously to make a plurality of nanocapsules.

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