Method of preparing silica nanocapsules and silica nanocapsules

Abstract

There is provided a method of preparing silica nanocapsules, the method comprising mixing a surfactant with water at a temperature that is above the gel-to-liquid transition temperature of the surfactant to form a mixture, passing the mixture one or more times through at least one pore to obtain a dispersion of vesicles, and adding a silica precursor to the dispersion of vesicles to form silica nanocapsules. Also provided is a silica nanocapsule formed from a vesicle template, and a method of delivering one or more types of molecules to a subject. In a specific embodiment, hollow silica nanocapsules having substantially lens-shaped are synthesized by employing dimethyldioctadecylammonium bromide (DODAB) or dioctadecyldimethyl ammonium chloride (DODAC) as the vesicle template and tetraethyl orthosilicate (TEOS) as the silica precursor.

Claims

1. A method of preparing substantially lens-shaped cargo-loaded silica nanocapsules, the method comprising: mixing a surfactant with water at a temperature that is above the gel-to-liquid transition temperature of the surfactant to form a mixture, the surfactant being selected from the group consisting of tetra alkyl ammonium halide; dimethyldioctadecylammonium bromide (DODAB); dimethyldioctadecylammonium chloride (DODAC); sulfate, phosphate or acetate salt of dimethyldioctadecylammonium (DODAX); dimethyldioctadecenylammonium bromide (DDAB); dimethyldioctadecenylammonium chloride (DDAC); sulfate, phosphate, acetate salt of dimethyldioctadecenylammonium (DDAX); bromide, chloride, sulfate, phosphate or acetate salt of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP); bromide, chloride, sulfate, phosphate or acetate salt of 1,2-dioleoyl-3-dimethylammonium propane (DODAP); bromide, chloride, sulfate, phosphate or acetate salt of N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium (DOTMA), and combinations thereof; passing the mixture one or more times through at least one pore to obtain a dispersion of vesicles; adding a silica precursor to the dispersion of vesicles to form substantially lens-shaped silica nanocapsules, the silicon precursor being selected from the group consisting of tetramethyl orthosilicate (TMOS), tetraethyl orthosilicate (TEOS), tetrapropyl orthosilicate (TPOS), tetrabutyl ortho silicate (TBOS) and combinations thereof; and mixing one or more types of hydrophilic cargo molecules with the substantially lens-shaped silica nanocapsules in the presence of a first organic solvent prior to adding a second organic solvent, to load the one or more types of hydrophilic cargo molecules into the substantially lens-shaped silica nanocapsules thereby obtaining substantially lens-shaped cargo-loaded silica nanocapsules, wherein the one or more types of hydrophilic cargo molecules is miscible with the first organic solvent, wherein the one or more types of hydrophilic cargo molecules is not miscible with the second organic solvent and wherein the first and second organic solvents are miscible with each other.

2. The method according to claim 1, wherein the step of adding a silica precursor to the dispersion of vesicles results in the silica precursor reacting with the vesicles to generate an organic solvent.

3. The method according to claim 2, wherein the organic solvent generated from the reaction between the silica precursor and the vesicles causes the shape of the vesicles to change from a substantially spherical shape to a substantially lens shape.

4. The method according to claim 1, wherein the at least one pore has a size of from 100 nm to 1300 nm.

5. The method according to claim 1, wherein the step of passing the mixture one or more times through at least one pore comprises passing the mixture at least four times through the at least one pore to reach a dispersion of vesicles having a bluish hue.

6. The method according to claim 1, wherein the step of adding a silica precursor to the dispersion of vesicles to form substantially lens-shaped silica nanocapsules is carried out under ambient conditions and/or wherein the silica precursor is added in an amount such that the surfactant to silica precursor ratio is from 1:5 to 1:40.

7. The method according to claim 1, further comprising non-thermally drying the substantially lens-shaped silica nanocapsules to obtain a powdered form of substantially lens-shaped silica nanocapsules.

8. The method according to claim 1, further comprising coagulating and/or filtrating the mixture/solution containing the one or more types of hydrophilic cargo molecules, the substantially lens-shaped silica nanocapsules, the first organic solvent and the second organic solvent to obtain the substantially lens-shaped cargo-loaded silica nanocapsules.

9. The method according to claim 1, wherein the method is substantially devoid of the addition of an organic solvent, the addition of a strong acid, the use of etching and the use of calcination, for the removal of a template used to form the substantially lens-shaped silica nanocapsules.

10. The method according to claim 1, wherein the first organic solvent comprises alcohol and the second organic solvent comprises ester.

Description

BRIEF DESCRIPTION OF FIGURES

(1) FIG. 1 is a schematic block diagram of a membrane extrusion setup 100 in an exemplary embodiment.

(2) FIGS. 2A-2B are particle size distribution plots obtained from dynamic light scattering (DLS) measurements of a DODAB vesicle in accordance with various embodiments disclosed herein.

(3) FIG. 3 is a graph showing variation in the z-average particle size of a DODAB vesicle obtained after different polycarbonate (PC) membrane pore sizes (100 nm, 200 nm, 400 nm, 600 nm and 1200 nm) are used in the membrane extrusion process in accordance with various embodiments disclosed herein.

(4) FIGS. 4A-4B are particle size distribution plots obtained from dynamic light scattering (DLS) measurements of silica nanocapsules in accordance with various embodiments disclosed herein.

(5) FIGS. 5,6 and 7 are microscopic images of the synthesized silica nanocapsules in accordance with various embodiments disclosed herein.

(6) FIG. 5 shows a conventional transmission electron microscopy (TEM) image of the hollow silica lens structure in solutions in accordance with various embodiments disclosed herein.

(7) FIGS. 6A-6C show cryogenic transmission electron microscopy (cryo-TEM) images of the hollow silica lens structure in solutions in accordance with various embodiments disclosed herein.

(8) FIGS. 7A-7D show scanning electron microscopy (SEM) images of dried hollow silica lens structure in accordance with various embodiments disclosed herein.

(9) FIGS. 8A-8B show cryogenic transmission electron microscopy (cryo-TEM) images of DODAB vesicles in accordance with various embodiments disclosed herein.

(10) FIG. 9 is a graph showing the thermogravimetric profiles of glycerol loaded silica nanocapsules in accordance with various embodiments disclosed herein.

(11) FIGS. 10-11 are microscopic images of synthesized silica nanocapsules (before and after glycerol loading) in accordance with various embodiments disclosed herein.

(12) FIG. 12 is a graph showing the percentage release of glycerol over time from glycerol loaded silica nanocapsules in accordance with various embodiments disclosed herein.

(13) FIG. 13 shows a broad scheme 200 of synthesizing a silica nanocapsule from a vesicle in accordance with various embodiments disclosed herein.

DETAILED DESCRIPTION OF FIGURES

(14) Example embodiments of the disclosure will be better understood and readily apparent to one of ordinary skill in the art from the following discussions and if applicable, in conjunction with the figures. It should be appreciated that other modifications related to structural and chemical changes may be made without deviating from the scope of the disclosure. Exemplary embodiments are not necessarily mutually exclusive as some may be combined with one or more embodiments to form new exemplary embodiments.

(15) FIG. 1 is a schematic block diagram of a membrane extrusion setup 100 for preparing a dispersion of vesicles in an exemplary embodiment. The setup 100 comprises a gas inlet 102, which allows gas to be charged into a pressure vessel 104. The pressure vessel 104 is first loaded with a mixture of surfactant in water, which undergoes membrane extrusion via the action of gas charging through inlet 102 into pressure vessel 104 and forcing the mixture through filter holder 106 containing membranes of specific pore sizes (not shown). The outlet of filter holder 106 is connected with a Teflon tube 110, which leads to a collection flask 112 where the resulting filtrate is collected. The pressure vessel 104 is temperature controlled at 60-65° C. using heating tape (not shown). The filter holder 106 and collection flask 112 are temperature controlled using a water bath 108.

(16) FIGS. 2A-2B are particle size distribution plots obtained from dynamic light scattering (DLS) measurements of a DODAB vesicle in accordance with various embodiments disclosed herein. FIG. 2A shows DLS measurements in a mixture of DODAB vesicle in water prior to membrane extrusion. FIG. 2B shows DLS measurements in a dispersion of DODAB vesicles after membrane extrusion using a polycarbonate membrane having a mean pore diameter of 400 nm. As shown, the particle size of a DODAB vesicle prior to membrane extrusion vary between 100 nm and 10,000 nm, with a z-average particle size of 1415 nm and a polydispersity index (PDI) of 0.586. After membrane extrusion, the average particle size of a DODAB vesicle is 144.2 nm.

(17) FIG. 3 is a graph showing variation in the z-average particle size of a DODAB vesicle obtained after different polycarbonate (PC) membrane pore sizes (100 nm, 200 nm, 400 nm, 600 nm and 1200 nm) are used in the membrane extrusion process in accordance with various embodiments disclosed herein.

(18) FIGS. 4A-4B are particle size distribution plots obtained from dynamic light scattering (DLS) measurements of silica nanocapsules in accordance with various embodiments disclosed herein. As shown, the particle size of the synthesized silica nanocapsules in accordance with various embodiments disclosed herein has a z-average particle size of 225 nm and a polydispersity index (PDI) of 0.128.

(19) FIGS. 5, 6 and 7 are microscopic images of the synthesized silica nanocapsules in accordance with various embodiments disclosed herein.

(20) FIG. 5 shows a conventional transmission electron microscopy (TEM) image of the hollow silica lens structure in solutions, with the scale bar representing 0.2 μm.

(21) FIGS. 6A-6C show cryogenic transmission electron microscopy (cryo-TEM) images of the hollow silica lens structure in solutions. In FIG. 6A, the scale bar represents 200 nm. In FIG. 6B, the scale bar represents 100 nm. In FIG. 6C, the scale bar represents 0.2 μm. As shown, the hollow silica lens particles in solution appeared as spherical in shape.

(22) FIGS. 7A-7D show scanning electron microscopy (SEM) images of dried hollow silica lens structure. In FIG. 7A, the scale bar represents 1 μm. In FIG. 7B, the scale bar represents 1 μm. In FIG. 7C, the scale bar represents 100 nm. In FIG. 7D, the scale bar represents 100 nm. As shown, the dried hollow silica lens particles are lens-shaped.

(23) FIGS. 8A-8B show cryogenic transmission electron microscopy (cryo-TEM) images of DODAB vesicles in accordance with various embodiments disclosed herein. FIG. 8A shows a cryo-TEM image of DODAB vesicles before addition of ethanol, with the scale bar representing 0.1 μm. FIG. 8B shows a cryo-TEM image of DODAB vesicles after addition of ethanol, with the scale bar representing 0.1 μm. As shown, the DODAB vesicle is spherical in shape before addition of ethanol. After addition of ethanol, the DODAB vesicle becomes lens-shaped.

(24) FIG. 9 is a graph showing the thermogravimetric profiles of glycerol loaded silica nanocapsules in accordance with various embodiments disclosed herein.

(25) FIGS. 10-11 are microscopic images of synthesized silica nanocapsules (before and after glycerol loading) in accordance with various embodiments disclosed herein. FIGS. 10A and 11A show SEM images of silica nanocapsules prior to loading glycerol. FIGS. 10B and 11B show SEM images of glycerol loaded silica nanocapsules. As shown, there is no substantial change to the morphology of the silica nanocapsules after glycerol is loaded. The silica nanocapsules remained lens-shaped.

(26) FIG. 12 is a graph showing the percentage release of glycerol over time from glycerol loaded silica nanocapsules in accordance with various embodiments disclosed herein. As shown, encapsulated glycerol is released from the lens shaped particles approximately over a period of two hours.

(27) FIG. 13 shows a broad scheme 200 of synthesizing silica nanocapsule 204 from a vesicle 202 in accordance with various embodiments disclosed herein. As shown in the figure, silica nanocapsule 204 having substantially lens-shaped morphology are obtained from using vesicle 202 as a template. The silica nanocapsule may be further loaded with one or more types of cargo, for example hydrophilic actives in its empty/hollow core 208 and subsequently act as a carrier for delivery and controlled release of the active molecules 210.

EXAMPLES

(28) Example embodiments of the disclosure will be better understood and readily apparent to one of ordinary skill in the art from the following examples and if applicable, in conjunction with the figures.

(29) The examples describe a method of preparing silica nanocapsules in a simple and direct process in accordance with various embodiments of the present disclosure. As will be shown in the following examples, embodiments of the presently disclosed method provide a cost-effective strategy to produce silica nanocapsules as elevated temperature and etching procedures were avoided and stable colloidal formulations (dispersion of vesicles) were formed in the absence of organic solvent. In summary, embodiments of the presently disclosed method require easy preparation and can be scaled up at ambient temperature without any specialized external energy inputs.

(30) As will be shown in the following examples, embodiments of the presently disclosed method synthesize silica nanocapsules having substantially lens-shaped morphology with well controlled structure size and aspect ratio in the nanoscale. The particle size and shape can be carefully tuned to give a unique lens-shaped morphology with a pore size of as low as 190 nm. These len-shaped silica nanocapsules showed high reproducibility and stability in water as compared to spherical silica microcapsules. These len-shaped silica nanocapsules can be configured to allow loading of hydrophilic molecules in a high loading capacity (of at least about 50%), which are useful in a wide array of applications.

Example 1

Preparation of Vesicle Template

(31) In this example, the preparation of vesicle template for the production of hollow silica nano lenses is demonstrated by using surfactant vesicle, for eg. dimethyldioctadecylammonium bromide (DODAB) or dioctadecyldimethyl-ammonium chloride (DODAC) as a soft template.

(32) Firstly, large unilamellar vesicles (LUV) were prepared by a membrane extrusion method. As shown in FIG. 1, the membrane extrusion setup 100 contains a high pressure stainless steel (SS) pressure vessel 104, which is connected to a SS filter holder 106 containing three stacked Isopore 47 mm polycarbonate (PC) membranes (Merck Millipore, 47 mm). The outlet of the filter holder was connected with a Teflon tube 110, from which the filtrate was then collected into a flask 112. The whole setup was temperature controlled at 60-65° C. using a heating tape for the pressure vessel and a water bath 108 for the filter holder and collection flask.

(33) Prior to extrusion, 0.631 wt % (10 mM) of DODAB or DODAC was prepared in aqueous solution and hydrated at 60° C., which is above the gel-to-liquid transition temperature (Tm) of DODAB or DODAC of 44° C., for 18 hrs under constant stirring speed of 300 rpm (using a 4-bladed stirrer at 45° C.). This was followed by loading into a pressure vessel 104 equipped with 7 bar argon.

(34) Extrusion was started by charging the argon into the pressure vessel 104 which forced the liquid through 200-400 nm polycarbonate membranes. The filtrate was collected into a collection flask 112 and immediately charged back into the pressure vessel 104 for a second extrusion. After each extrusion, the size of the vesicles was determined by dynamic light scattering (DLS). A total of 8 cycles of extrusion was completed and the resulting vesicles dispersion appeared as a nice bluish dispersion, which was allowed to cool to room temperature naturally.

(35) The following DLS size characterization results demonstrate the effectiveness of size control using the membrane extrusion method described herein. As will be shown in the following figures, the results indicated that a dispersion of DODAB vesicles having substantially uniform size is prepared successfully with membrane extrusion.

(36) As shown in FIG. 2A, prior to membrane extrusion, a DODAB vesicle has a broad particle size distribution. The particle size vary over a wide range between 100 nm and 10,000 nm with a polydispersity index (PDI) of 0.586. After undergoing membrane extrusion with a membrane having a mean pore diameter of 400 nm, the average size measured for a DODAB vesicle is about 144 nm with a polydispersity index (PDI) of 0.151 as shown in FIG. 2B, which is indicative of a narrow size distribution and a successful control of the particle size with the use of membrane extrusion in obtaining substantially uniform vesicles.

(37) The effect of varying the pore size of the membrane used during extrusion on the average particle size of the resulting DODAB vesicle obtained was also studied and the results are shown in FIG. 3. The results indicated that by specifically selecting a suitable membrane pore size during membrane extrusion, the size of the vesicles can be carefully controlled to give substantially uniform DODAB vesicles of the desired size.

Example 2

Synthesis of Hollow Silica Nano Lenses Via Vesicle Templatinq

(38) In this example, a direct synthesis of hollow silica nano lenses is demonstrated via vesicle templating. The experiments are conducted at a laboratory scale but it would be understood that a further scale-up of the method may be carried out, for example by scaling to an industrial process.

(39) In a typical experiment, the vesicle solution was used for hollow silica nano lenses synthesis without adjustment of pH. The reaction was started in a sequential step by adding silicon precursor, i.e. silicon alkoxide to the vesicle dispersion via a programmed syringe pump. The silicon alkoxide used can be tetraethyl orthosilicate (TEOS) or tetramethyl orthosilicate (TMOS). The concentration of silica precursor can be changed, for example, the silica precursor is added to the vesicle solution at a ratio of [DODAB]:[silica precursor]=1:10, 1:20 or 1:30. The reaction mixture was then vigorously stirred.

(40) At the beginning of the reaction, an emulsion was present which disappeared as the reaction proceeded. Without being bound by theory, it is believed that the presence of the emulsion is due to the formation of oil droplets by the hydrophobic silica precursor. As the reaction proceeded, the oil phase disappeared as a result of hydrolysis of the hydrophobic silica precursor. At every desired instant, the pH can be adjusted by addition of ammonia to influence the sol-gel chemistry of the silica growth. All experiments were performed at room temperature.

(41) The samples were aged for at least 1 day before transmission electron microscopy (TEM) and scanning electron microscopy (SEM) visualization studies, and freeze dried to get a dried powder.

(42) Characterization Studies of Hollow Silica Nano Lens Particles

(43) Characterization studies of embodiments of the hollow silica nano lens particles were performed with various methods including dynamic light scattering (DLS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM).

(44) The following characterization results indicated that silica nanocapsules having well-controlled structure size and aspect ratio in the nanoscale were successfully synthesized with the method disclosed herein. Electron microscope images also reveal that silica nanocapsules having a substantially lens-shaped morphology were synthesized.

(45) The size of the hollow silica nano lens was determined by dynamic light scattering (DLS). As shown in FIGS. 4A-4B, the average size of the hollow silica nano lens prepared according to the method disclosed herein is about 190-250 nm (z average is 225 nm), with a polydispersity index (PDI) of 0.128.

(46) Two different electron microscopy methods were used to visualize the hollow silica lens structure in solutions, namely conventional transmission electron microscopy (TEM) and cryo-transmission electron microscopy (Cryo-TEM), while scanning electron microscopy (SEM) was used for imaging the dried hollow silica nano lens particles.

(47) FIG. 5 shows the normal TEM image of the hollow silica lens structure in solutions. FIGS. 6A-6C show the cryo-TEM images of the hollow silica lens structure in solutions. FIGS. 7A-7D show the SEM images of the dried hollow silica lens structure. From the morphology study, the Cryo-TEM imaging in FIGS. 6A-6C shows that the particles in solutions appeared as spherical in shape. The SEM images FIGS. 7A-7D show that the dried particles are lens-shaped. It should be appreciated that when viewed in certain different orientations, the silica lens structure may appear as shapes other than lens-shaped even though there is at least one orientation at which the structure would be viewed as lens-shaped. For example, when SEM is used, due to the need to dry the sample on the grid, in some instances the hollow silica lens observed may be flat on the surface so they appear as circles, e.g. pancakes or flattened spheres. In cryo-TEM, where the wet sample is frozen, the ability to capture the nanocapsules in various orientations may be enhanced and thus in some instances the lens-shaped structure may be more apparent.

Example 3

Shape Change in DODAB Vesicle from Spherical to Lens-Shaped

(48) In this example, the morphology of the DODAB template is studied with Cryo-TEM imaging to primarily examine the formation of the unique silica lens shape from the spherical DODAB vesicle template.

(49) Without being bound by theory, it is believed that the shape change of DODAB template from spherical to lens-shaped is due to the presence of the organic solvent “ethanol” in water. DODAB vesicle has a self-assembled bilayer structure and is a flexible and permeable template in water media. During hydrolysis and condensation reaction of TEOS to form SiO.sub.2, ethanol is generated as a side product on the DODAB bilayer. It is therefore believed that the presence of organic solvent “ethanol” in water leads to the shape change of DODAB template from spherical to lens-shaped.

(50) The effect of ethanol on the morphology of the DODAB vesicle is demonstrated in FIGS. 8A and 8B using cryo-TEM imaging. FIG. 8A shows that before addition of ethanol, a DODAB vesicle has a spherical shape. After addition of ethanol, FIG. 8B shows that the DODAB vesicle is lens-shaped. Therefore, in summary, without being bound by theory, it is believed that the lens-shaped morphology of the synthesized silica nanocapsules in accordance with various embodiments disclosed herein may be attributed to the lens-shaped morphology of DODAB vesicle template formed via generation of ethanol during hydrolysis and condensation reaction of TEOS.

Example 4

Loading Capacity Studies Using Glycerol

(51) In this example, the synthesized silica nanocapsules in accordance with various embodiments disclosed herein is loaded with hydrophilic molecules, for example, glycerol and studied by using SEM imaging. The loading capacity of synthesized silica nanocapsules in accordance with various embodiments disclosed herein for glycerol is also examined.

(52) The loading capacity of hollow silica nano lens for glycerol is determined by a post loading process using ethanol and ethyl acetate (EA). Dried hollow silica nano lens particles were mixed with glycerol and ethanol solution. Ethyl acetate (EA) was added into the silica-glycerol ethanol mixture where silica and glycerol were mixed well and stirred for 30 mins. Ethanol was dissolved in EA and EA-insoluble glycerol was forced to stay in the silica nano lens in the EA mixture. Hydrophilic active loaded silica nano lens particles were rinsed with EA 3 times and dried at room temperature. Hydrophilic active loaded silica nano lens particles were characterized by thermogravimetric analysis (TGA) to measure loading capacity. As shown in FIG. 9, TGA result of the glycerol loaded silica nano lens indicated that the loading capacity was 40%. The results also indicated that the glycerol loaded silica nano lens are thermodynamically stable at high temperatures e.g., 200° C.

(53) The different loading trials are provided in a table below. The weight of the silica nano lens particles was measured before and after loading of glycerol and the percentage of glycerol loaded was calculated. It was observed that the synthesized silica nano lens particles can be loaded with more than 60% of glycerol.

(54) TABLE-US-00001 TABLE 1 Maximum loading of glycerol attained in different batches of silica lens particles performed in various experiments. Weight of Percentage Silica Weight of Weight of of glycerol Sample (before Glycerol Silica (after loaded Sample Name loading) (g) (g) loading) (g) (%) 1 Silica Lens 0.2982 0.5908 0.3767 60.31 2 Silica Lens 0.3031 0.7018 0.3968 64.53 3 Silica Lens 0.2959 0.6045 0.3160 58.55 4 Silica Lens 0.2454 0.5002 0.2836 55.024

(55) Characterization Studies of Glycerol Loaded Silica Nano Lens Powder

(56) FIGS. 10A and 11A show the SEM images of silica lens particles before glycerol is loaded. FIGS. 10B and 11B show the SEM images of silica lens particles after loading glycerol. As shown, there is no substantial change to the lens-shaped morphology of the silica nanoparticles after loading glycerol, which is evident that the silica nanoparticles having substantially lens-shaped are chemically and physically stable (e.g. no breakage).

(57) Although silica nano powder is not biocompatible by inhalation, it may be appreciated by a person skilled in the art that loading glycerol in silica nano lens imparts a higher density on the silica nano lens powder. Reference is made to the density of glycerol at 1.26 g/cm.sup.3. As a result, the loaded silica nano lens powder would not easily escape and disperse in air. Moreover, the glycerol loaded silica lens powder may be formulated with needed additives (surfactant, dye, essential oil, etc.) for further consumer care applications, thereby eliminating any chances of inhalation into the human body.

Example 5

Timed Release Studies of Glycerol Loaded Silica Nanocapsules

(58) In this example, timed release studies were conducted on the glycerol loaded silica nanocapsules in accordance with various embodiments disclosed herein. Firstly, the synthesized silica nano lens particles were loaded with glycerol. Then, they were suspended in aqueous media and compared with controls.

(59) The percentage of glycerol released from the lens-shaped particles over a period of 80 minutes is estimated using standard enzymatic assay and the results are shown in FIG. 12. In water, unencapsulated glycerol instantly dissolves. On the other hand, encapsulated glycerol is released gradually from the lens-shaped particles over a period of approximately two hours. Advantageously, this result indicates that the encapsulation of glycerol in the lens-shaped particles displayed potential in achieving a sustained release profile of moisturizing hydrophilic actives for long periods of time.

(60) Applications

(61) Various embodiments of the present disclosure provide silica nanocapsules that are submicron in size, have a unique morphology that is substantially lens-shaped and have well controlled structure size and have an aspect ratio in the nanoscale. For example, it has been shown that the particle size and shape can be carefully tuned to give a unique lens-shaped morphology with a pore size of as low as 190 nm. Embodiments of the silica nanocapsules disclosed herein showed high reproducibility and stability in water as compared to spherical silica microcapsules.

(62) In various embodiments, the silica nanocapsules disclosed herein can be scalable and are a new class of nanocarriers that can be used in a wide array of applications such as in therapy, diagnostics, pharmaceuticals, cosmetics, cosmeceuticals and nutraceuticals.

(63) In various embodiments, the silica nanocapsules disclosed herein have an outer shell which encapsulates a substantially hollow interior configured to allow loading of many different types of molecules (such as different hydrophilic actives) in a high loading capacity (of at least about 50%). For example, the silica nanocapsules disclosed herein have a high flexibility in loading various types of hydrophilic actives such as moisturizers (glycerol), water soluble dye, water soluble vitamins such as vitamins B, B6, C, riboflavin, and hydrophilic natural product.

(64) In various embodiments, the silica nanocapsules disclosed herein are biocompatible and biodegradable. In various embodiments, the silica nanocapsules disclosed herein have an enhanced sensory effect on the skin and provide a good desirable feel to the skin, thus making them attractive for use as skin brighteners, night creams, facial masks, anti-agers and moisturizers in cosmetic, skin care and personal care applications.

(65) Various embodiments of the present disclosure provide a simple and direct synthesis of the silica nanocapsules disclosed herein. For example, the process involves easy preparation from a soft vesicle template in the absence of debris. Stable colloidal formulation (dispersion of vesicles) is formed in the absence of organic solvents and harsh tedious procedures such as high temperature calcination and/or etching are not required, thereby making the production process efficient and cost-effective on a large scale. The present disclosure has demonstrated the principles involved, and opens the way for further scale-up in many applications.

(66) It will be appreciated by a person skilled in the art that other variations and/or modifications may be made to the embodiments disclosed herein without departing from the spirit or scope of the disclosure as broadly described. The present embodiments are, therefore, to be considered in all respects to be illustrative and not restrictive.