Silicon vesicles and entrapment

Abstract: A method of entrapping a water-soluble substance in vesicles formed from a siloxane surfactant is carried out by dissolving the substance to be entrapped in water, adding a siloxane surfactant, mildly agitating the mixture and removing excess of water and substance. Further, water-insoluble substances can be entrapped in the vesicles by dissolving the substance to be entrapped in the siloxane surfactant and mildly agitating the substance and the siloxane surfactant. Suitable siloxane surfactants are R-[Si(Me)₂O]₁₄-Si(Me)₂-R in which R is -(CH₂)₃(OCH₂CH₂)₇OH, R-[Si(Me)₂O]₁₄-Si(Me)₂-R in which R is -(CH₂)₃(OCH₂CH₂)₁₂OH, Me₃SiO[Si(Me)₂O]₂₂-[SiMeRO]₂-SiMe₃ in which R is -(CH₂)₃(OCH₂CH₂)₁₂OH and Me₃SiO[Si(Me)₂O]₁₀₃-[SiMeRO]₁₀-SiMe₃ in which R is -(CH₂)₃(OCH₂CH₂)₁₂OH.

Description: This invention is directed to siloxane surfactants and to the formation of vesicles from siloxane surfactants. More particularly, the invention is directed to the use of vesicles formed from siloxane surfactants for the entrapment of water-soluble and water-insoluble substances. The first problem solved by the present invention is to find a siloxane molecule which is able to form vesicles. The second problem solved is to develop a use of such vesicles formed from siloxane surfactants for substance entrapment. Because of the nature of the siloxane linkage, siloxane surfactants do not follow the usual rules of surfactant activity with regard to aggregate formation and solubilization. Therefore, to even find a siloxane molecule which is able to form vesicles is quite surprising and unexpected. What is even more amazing, is that having once pinpointed a particular siloxane molecule for vesicle formation, that the vesicle formed from the siloxane surfactant would also be useful to entrap various substances. The advantages and benefits derived by the use of siloxane surfactants in vesicle formation and substance entrapment, include the fact that siloxanes possess a non-hydrocarbon character and, therefore, provide a different set of physical properties than is currently available with hydrocarbon-based surfactant molecules. Secondly, siloxane surfactants have been found to form vesicles "spontaneously" on contact with water and, therefore, they eliminate the use of energy intensive processes such as sonification, which are required for nonsiloxane based surfactants. Thirdly, because the siloxane backbone offers chemically reactive sites, it is possible to easily exploit the formation of polymerized vesicles. Aqueous dispersions of lipids in the form of particles having a lamellar structure, termed liposomes or vesicles, are excellent vehicles for the delivery or encapsulation of pharmaceutical substances. Handjani-Vila, et al. in the Int. J. Cosmetic Sci. , 1 (1979) 303, in an article entitled "Dispersions of lamellar phases of nonionic lipids in cosmetic products", have demonstrated the advantages that can be obtained by the application of such systems to the skin, in particular to the use of nonionic lipids in aqueous dispersions. The synthetic nonionic lipids described by Handjani-Vila are used either alone or as commonly practiced in combination with cholesterol or dicetylphosphate. Handjani-Vila showed that vesicles formed by nonionic lipids can form either a total cosmetic system alone or a vehicle for water soluble active substances. As a cosmetic system, they facilitate the supply of lipids and water to the stratum corneum and are able in the absence of a moisturizer to prevent the occurrence of dry skin. As a vehicle, they also effectively facilitate the transport of diverse substances such as moisturizers, tanning agents and sunscreens, into the stratum corneum and, furthermore, prevent subsequent elimination by water washing. These formulations were clearly less aggressive and more effective than conventional emulsion based lotions and creams. In general terms, a lipid is defined in the " Dictionary of Colloid and Surface Science ", by Becher & Dekker, New York, 1990, to be any one of a group of organic compounds, characterized by a greasy feel, insoluble in water, but soluble in a number of organic solvents, such as an alcohol or ether; or as a fat. However, in this context, lipid means more specifically the class of surface active lipids, for example, the phospholipids or lecithins, which are dispersible into water to form lamellar phase particles or liposomes. Handjani-Vila also defined lipid to be a synthetic, tailor-made material of the structure R-[O-CH 2 -C(CH 2 OH)H] n -OH in which R is an alkyl group. These materials are said to be branched chain polyglycerol ethers. The advantage of this synthetic material is the avoidance of considerable problems of reproducibility and stability arising from the use of lecithins. Lautenschlager in Cosmetics & Toiletries , 105 (1990) 89, in an article entitled "Liposomes in dermatological preparations Part I", and in Cosmetics & Toiletries , 105 (1990) 63, in an article entitled "Liposomes in dermatological preparations Part II", expands the class of nonionic lipids which form vesicles to include ethoxylated fatty alcohols and synthetic, linear or branched chain polyglycerol ethers with R being a linear or branched-chain saturated hydrocarbon residue such as hexadecyl. Lautenschlager also states that such nonionic lipids are usually formulated on a 1:1 basis with cholesterol or dicetyl phosphate, because they do not form vesicles on their own. Other bilayer forming amphiphiles or surfactants which form vesicles include dialkyl phosphates and N,N-dimethyl-N,N-dialkyl ammonium salts. Liposomes are defined by Lautenschlager as spherical, globular, vesicles, the membranes of which consist of a bilayer of amphiphilic lipid molecules. Most cosmetic and pharmaceutical liposomes are composed of various phospholipids of natural, semi-synthetic and synthetic origin, with the major component being phosphatidylcholine. Minor components can include phosphatidylethanolamine, phosphatidylinositol and phosphatidic acid. The term vesicle refers to a structure consisting of a closed bilayer membrane envelope. Vesicles are often globular or tubular in shape but can also be quite irregular. In the context of the present invention however, vesicles made using siloxane surfactants are not liposomes, because they are not actually prepared from materials recognized as lipids. A liposome is rather a specific type of vesicle prepared from lipid amphiphiles. The manufacturing processes for vesicles taught in the prior art depend on the use of high energy homogenizers and usually consist of two steps which are (1) mixing the amphiphile with water, followed by (2) making the vesicles uniform in size distribution. Excess water soluble substance outside the vesicles can be removed in a third step, but for cosmetic applications this third step is not necessary. Lautenschlager discusses various mechanisms of action of liposomes in cosmetic and dermatological formulations, including their use as a transport system for other active ingredients and their use as active materials. The latter use is a manifestation of the similarity between the lipids used to form the liposomes and the lipids which make up the bilayers of skin cell walls, which would not necessarily hold true for the siloxane surfactants of the present invention. Some of the water insoluble substances of current interest for cosmetic vesicle delivery are vitamin E, retinoids, steroids and other lipophilic actives. Water soluble natural moisturizing factors have been incorporated into the interior of vesicles by Lautenschlager. Lautenschlager includes a range of potential uses of vesicles in cosmetic and dermatological formulations which exploit their unique properties. As noted by Lautenschlager, the phase transition temperature, that is gel-to-fluid, is an important criteria in the selection of a basic liposomal formulation. One of the unique features of the siloxane surfactants of the present invention; however, is that the siloxane surfactants form vesicles without any such phase transition between 0-90°C. This advantage of our invention over the teaching in Lautenschlager allows formulators more flexibility with regard to processing temperatures and storage stability. This feature, advantage and benefit is due to the low melting point of the methylated siloxane portion of the surfactant molecules of our invention. The use of vesicles in cosmetics or dermatological formulations is limited by their compatibility with other components of the formulation and this is indicated by Lautenschlager. In particular, the presence of other surfactants, ethanol and propylene glycol, are known to interfere with the vesicles. For example, other surfactants often transform vesicles into mixed micelles. Lautenschlager notes, however, that some vesicle forming surfactants are more stable to these effects than others. Since siloxane surfactants do not form mixed micelles with organic surfactants as readily as other organic surfactants, as noted by Hill in Mixed Surfactant Systems , Holland & Rubingh, ACS Symp. Ser., 501 (1992) 278, in an article entitled "Interactions between siloxane surfactants and hydrocarbon surfactants", it is reasonable to expect that vesicles formed from siloxane surfactants would be more tolerant of the presence of other surface active agents. In the past, cosmetic products relied on simply combining moisturizing or cell regenerating agents with an emulsion or a cream base. However, cosmetic products have now reached the stage where liposomes can encapsulate active ingredients thought to be necessary for the skin, so that they may be applied directly to skin cells, as noted by Suzuki et al in Cosmetics & Toiletries , 105 (1990) 65, in an article entitled "The application of liposomes to cosmetics". Suzuki teaches that an important benefit of liposomal encapsulation is the enhanced transport of the active ingredient into the stratum corneum when encapsulated in a liposome. Thus, encapsulation for cosmetic uses not only has the objective of protecting the sensitive active, but of enhancing the transport of the active into the stratum corneum. This effect relies on the similarity of the lipid bilayers of the liposome with those of the cell walls of the skin and functions differently for the siloxane surfactant vesicles described in the instant invention. Such a difference represents a very surprising and exploitable advantage for the siloxane surfactants of this invention. Thus, the physiology of the skin is not so simple that all questions, regarding how and to which cells liposomes "fuse" in penetrating the skin barrier, can be answered with any certainty. Clearly, the potential exists for vesicles formed from siloxane surfactants to present an entirely different behavior for the technologist to exploit, which constitutes another added advantage and benefit provided by this invention over the systems described in the prior art. Suzuki states that organic solvents are used in most liposome preparation methods. This creates a safety problem from solvent residues in the final product. Since no such solvent is required to efficiently form vesicles using siloxane surfactants, this represents another distinct and decided technical advantage for the instant siloxane technology. Cosmetic-carrying liposomes can be prepared by a variety of techniques. All such techniques involve an intensive agitation or shear of aqueous suspensions of lipids by means of sonication, high pressure extrusion or mixing of high pressure jets, as shown for example by Strauss in J. Soc. Cosmet. Chem. , 40 (1989) 51, in an article entitled "Liposomes: from theoretical model to cosmetic tool". Liposomes have become increasingly important as a vehicle for the controlled delivery of cosmetics. This development parallels the application of liposomes for drug delivery. Liposomes can encapsulate many types of cosmetic agents. Such encapsulation offers improved uptake, adhesion and persistence of active ingredients in skin and hair products and this is noted by Strauss. Strauss also outlines procedures for the preparation of liposomes by incorporating either water soluble or water insoluble active ingredients. Mitchell et al. in the J.C.S. Faraday Trans. 2, 77 (1981) 601, in an article entitled "Micelles, vesicles and microemulsions"; and Israelachvili et al. in the J.C.S. Faraday Trans 2, 72 (1976) 1525, in an article entitled "Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers"; each teach a method for calculating a so-called surfactant parameter "S" which quantifies the shape of the surfactant molecule. The numerical value of S is said to predict the type of aggregate micelle or vesicle the surfactant will prefer to form in an aqueous solution. Values of S between 0.5 and 1.5 are stated to indicate a tendency to form bilayer structures including vesicles. This concept was derived for surfactants containing linear alkyl hydrophobic groups. Its application to the siloxane surfactants of the present invention, particularly the polymeric type, however, is not at all apparent; although Hill et al. in Langmuir , 9 (1993) 2789, in an article entitled "Lyotropic liquid crystal phase behavior of polymeric siloxane surfactants", provide procedures including bond lengths needed to apply this calculation to siloxane surfactants. The most preferred siloxane surfactant structures for forming vesicles are said to be those for which 0.5 ≤ S ≤ 1.5, as calculated using the procedures of Hill et al. Procedures for the preparation of large unilamellar vesicles from conventional phospholipid amphiphiles are shown in U.S. Patent 4,078,052. The patented procedure includes sonication, followed by an intricate manipulation of the solution using Ca 2+ ions and chelating agents. U.S. 4078052 illustrates the energy intensive and difficult procedures which must be used to prepare vesicles from phospholipids. Such complex procedures are not required, however, according to our invention. Talsma et al in BioPharm , October (1992) 36, in an article entitled "Liposomes as drug delivery systems, part I: preparation"; and in Pharmaceutical Technology , November (1992) 53, in an article entitled "Liposomes as drug delivery systems, part II: characterization"; and further in Pharmaceutical Technology , January (1993) 36, in an article entitled "Liposomes as drug delivery systems, part III: stabilization"; state that vesicles formed by phospholipid bilayers dispersed in aqueous media are used in cosmetics and dermatalogicals and are potential carriers for diagnostic agents and pharmaceuticals. A few of such liposome based parenteral and dermal drug formulations for human use are now on the market. In the near future, one can reasonably expect more liposomal formulations for the solubilization of lipophilic drugs, for active and passive drug targeting, for sustained release of drugs or proteins and for antigen presentation; and all of these expectations are noted by Talsma et al. But some unsolved problems related to large scale production, stabilization and safety of liposomes, may hamper development of this technology. Contrastingly, vesicles formed using the siloxane surfactants of this invention offer a potential for overcoming these problems, because of the different physical properties and the distinctly non-lipid character of the vesicles formed from siloxane surfactants. The advantages and benefits of the present invention can be better appreciated when it is considered that prior to our invention, the surfactants known to form vesicles were principally dialkyl cationic surfactants and/or phospholipids. There is no structural resemblance between these organic surfactants and the siloxane surfactants employed herein. Rather, our siloxane surfactants are polymeric molecules which can contain a wide variety of molecular species. It is surprising that such a polydisperse mixture would form a highly organized structure such as a vesicle. It is even more unexpected that complex molecules such as siloxane surfactants would pack themselves together into an orderly, liquid crystalline state. In addition, because of the presence in our siloxane surfactant molecule of the ≡Si-O-Si≡ linkage, siloxane surfactants do not follow the usual patterns of surfactant activity. While siloxane surfactants are useful in the manufacture of polyurethane foam and as wetting agents or surface-feel modifiers, the capability of siloxane surfactants to also form vesicles for the entrapment of water-soluble and water-insoluble substances is entirely unexpected. Comparable organic materials having similar uses are not known to possess the added capability of vesicle formation and entrapment. A principle benefit and advantage derived by the practice of this invention is the facility with which the siloxane surfactants forms vesicles. Prior to our invention, the formation of stable vesicles from known dialkyl cationic surfactants and phospholipids required very involved and special procedures including the necessity for high energy mixing in their preparation. According to our invention, however, vesicles formed from siloxane surfactants are formed with relative ease and they are formed simply as a matter of mixing the siloxane surfactant with water. Comparable organic polymers on the other hand which are not known to form vesicles require much more energy, time and special procedural and processing steps, just to disperse them into a solution. The single Figure 1 of the drawing is a cryo-TEM micrograph of a freshly prepared, ten percent solution of a siloxane surfactant having the formula R-[Si(Me) 2 O] 14 -Si(Me) 2 -R wherein R is -(CH 2 ) 3 (OCH 2 CH 2 ) 12 OH in water at 20°C. Figure 1 demonstrates that this siloxane surfactant forms vesicles in water. It should be noted that the photograph shows many single and multi-walled large vesicles. In particular, this micrograph shows the presence of a variety of structures including unilamellar and multilamellar vesicles which range in shape from globular to long tubules. The variety of morphologies visible reflects the polydispersity of the siloxane surfactant. The siloxane surfactant represented in Figure I is one of the three siloxane surfactants set forth below in Examples I-III. Vesicles, sometimes referred to as liposomes, are surfactant molecules which form closed layered structures when dispersed in water. They are constructed of alternating layers of surfactant bilayers which are spaced by aqueous layers or compartments arranged in approximately concentric circles. If multilayered vesicles are subjected to ultrasound or vigorous agitation, the multilayered structure can be disrupted to produce a single bilayer assembly, which consists of a unilamellar vesicle in which a portion of the aqueous phase is entrapped within a single bilayer assembly. Typically, a vesicle has a diameter of 30 to 100 nanometers. Vesicles are able to entrap within their assembly a portion of the aqueous phase present at the time of their formation. This provides a convenient vehicle for the inclusion within the vesicle of water-soluble substances. Water and hydrophilic compounds are entrapped in the central cavity of the vesicle between planes of the hydrophilic head groups. Water-insoluble substances can also be incorporated into the vesicle, although the water-insoluble substance locates itself between planes of the hydrophobic head groups of the vesicle system. Among suitable examples of the various types of water-soluble substances which can be entrapped by our invention are salicylic acid; Vitamin C; water-soluble deodorant substances; sodium stearate-based antiperspirant salts; water-soluble preservatives; water-soluble sunscreens; glycerine; enzymes; alpha-hydroxy substances such as glycolic acid; water; dyes such as VIOLET No. 2 and water-soluble drugs. Suitable examples of water-insoluble substances which can be entrapped according to the invention are Vitamin A; water-insoluble preservatives; water-insoluble sunscreens; water-insoluble drugs; pigment dispersions; and polydimethylsiloxane fluids. Water-soluble substances are entrapped by dissolving the substance in water, forming and adding an appropriate siloxane surfactant, minimally agitating the mixture by mild shaking and removing excess substance in the external phase by centrifugation, by dialysis or by size exclusion chromatography. Water-insoluble substances are entrapped by dissolving the substance in an appropriate siloxane surfactant, followed by minimum agitation of the mixture by mild shaking. No removal step by centrifugation, dialysis or size exclusion chromatography is required. A suitable co-solvent such as chloroform may be included, however. The vesicle containing the entrapped water-insoluble substance can then be used by dispersing it in an aqueous system, if desired. The siloxane surfactants of our invention have been found to form vesicles when used in low concentration levels up to the lower boundary of the lamellar liquid crystal phase. Thus, our siloxane surfactants are employed in an amount of from 0.1 percent by weight to 40.0 percent by weight, preferably in a range of from 0.5 to 20.0 percent by weight. The water-soluble substance which is entrapped in the vesicles formed from these siloxane surfactants is employed in an amount of from 0.1 percent by weight to 10.0 percent by weight, with the balance of the composition being water. The water-insoluble substance which is entrapped in the vesicles formed from these siloxane surfactants is likewise employed in an amount of from 0.1 percent by weight to 10.0 percent by weight, with the balance of the composition being a suitable co-solvent such as chloroform. Siloxane surfactant compounds for the formation of vesicles of this invention are represented by: In formulas (I) to (III), Me is methyl. R is a radical which can be methyl, -(CH 2 ) x O(C 2 H 4 O) y (C 3 H 6 O) z R' or -(CH 2 ) x N + R 3 ''A - , with the proviso that at least one R radical in the molecule is not a methyl radical. R' is either hydrogen atom, a methyl radical or an acyl radical. R'' is an alkyl radical having from one to six carbon atoms, a phenyl radical, a benzyl radical or the radical -CH 2 CH 2 OH. The counterion A - is chloride, bromide, iodide, cyanide, a methyl sulfate radical, a salicylate radical or a dodecylsulfate radical. In formulas (I) and (II), a has a value of 0 to 200; b has a value of 0 to 50; with the proviso that a and b cannot both be zero. In formulas (I) to (III), x has a value of 3 to 6; y has a value of 4 to 30; and z has a value of 0 to 5. The following four siloxane surfactants were formed into vesicles according to the present invention and are representative of the types of organosilicon compounds set forth in the generic formulas: R-[Si(Me) 2 O] 14 -Si(Me) 2 -R in which R is -(CH 2 ) 3 (OCH 2 CH 2 ) 7 OH, R-[Si(Me) 2 O] 14 -Si(Me) 2 -R in which R is -(CH 2 ) 3 (OCH 2 CH 2 ) 12 OH, Me 3 SiO[Si(Me) 2 O) 22 -[SiMeRO] 2 -SiMe 3 in which R is -(CH 2 ) 3 (OCH 2 CH 2 ) 12 OH and Me 3 SiO[Si(Me) 2 O] 103 -[SiMeRO] 10 -SiMe 3 in which R is -(CH 2 ) 3 (OCH 2 CH 2 ) 12 OH. In these formulas, Me is the methyl radical. Example I Vesicles were prepared from siloxane surfactants and their entrapping efficiency was evaluated. Three different siloxane surfactant molecules were employed which corresponded to the compounds Me 3 SiO[Si(Me) 2 O] 22 -[SiMeRO] 2 -SiMe 3 , R-[Si(Me) 2 O] 14 -Si(Me) 2 -R and Me 3 SiO[Si(Me) 2 O] 103 -[SiMeRO] 10 -SiMe 3 . In all of these siloxane surfactants, R was -(CH 2 ) 3 (OCH 2 CH 2 ) 12 OH. There was initially prepared two milliliters of a two weight percent solution of each siloxane surfactant in a buffer solution containing 60 mM calcein which is a water-soluble fluorescent dye. Calcein, also known as Fluorexon, is bis[N,N-bis(carboxymethyl)aminomethyl]fluorescein. At the concentration employed, the calcein dye was self-quenching and not fluorescent and the three solutions were brown in color. Each solution contained vesicles formed from a siloxane surfactant entrapping a fraction of the solution volume in an excess of the solution. The calcein dye was removed from the solution external to the vesicles by size exclusion chromatographic separation using a SEPHADEX® column and also by ultracentrifugation. Once the calcein dye external to the vesicles had been removed, any leakage of the dye out of the vesicle was detectable, because the calcein dye became fluorescent in the lower concentration of the environment external of the vesicle. The leakage rate was accordingly quantified by monitoring fluorescence as a function of time. Example II One-half of each of the solutions prepared in Example I was ultracentrifuged at 40,000 rpm (150,000 G) for thirty minutes. A small brown pellet of vesicles formed from the siloxane surfactant was visible in the bottom of each of the three solutions. The supernatant liquid was poured off and the vesicles were redispersed in a fresh buffer solution and again ultracentrifuged under the conditions noted above. Again a small brown pellet appeared at the bottom of each of the three solutions. Once more, the supernatant liquid was poured off and the vesicles were once again redispersed in a fresh buffer solution. The solutions each appeared to be light brown in color, which indicated the presence of vesicles entrapping the concentrated calcein dye solution. Fluorescence increased very slowly which indicated that the vesicles formed from the siloxane surfactant did not leak rapidly. The addition of twenty microliters of a ten percent by weight solution of sodium dodecylsulfate (SDS) dissolved the vesicles and caused a sudden and dramatic rise in fluorescence, which demonstrated conclusively that entrapment had occurred for each of the three siloxane surfactants. The entrapped volume was determined with the aid of a standardization curve for calcein dye. Example III The other one-half of each of the three solutions prepared in Example I was passed twice through a small pre-packed size exclusion SEPHADEX® column and a cloudy middle fraction was collected. The solutions were washed through the column using an iso-osmotic buffer solution. SEPHADEX® is a trademark of the Pharmacia Biotechnology Group of Piscataway, New Jersey and is a dry insoluble powder column packing composed of microscopic beads that are synthetic organic compounds derived from the polysaccharide dextran. The dextran chains are crosslinked to provide a three-dimensional network and functional ionic groups are attached to the glucose units of the polysaccharide chains by ether linkages. In the SEPHADEX® size exclusion column, small calcein dye molecules "visit" the holes in the SEPHADEX® column packing and, therefore, pass through the column at a much slower rate than the vesicles formed from the siloxane surfactant. Following treatment of the solutions in the SEPHADEX® column, the solutions each appeared to be light brown in color, which indicated the presence of vesicles formed from a siloxane surfactant entrapping the original concentrated calcein dye solution. Fluorescence increased very slowly which indicated that the vesicles did not leak rapidly. The addition of twenty microliters of a ten percent by weight solution of sodium dodecylsulfate (SDS) dissolved the vesicles and caused a sudden and dramatic rise in fluorescence, which demonstrated conclusively that entrapment had occurred for each of the three siloxane surfactants. The entrapped volume was determined with the aid of a standardization curve for calcein dye. The following additional example is set forth for the purpose of further illustrating the invention and to provide more evidence of entrapment of materials with a siloxane surfactant. Example IV A siloxane surfactant having the formula R-[Si(Me) 2 O] 14 -Si(Me) 2 -R in which R is -(CH 2 ) 3 (OCH 2 CH 2 ) 7 OH, was added to an aqueous solution of Bromocresol Purple dye at a pH of about four. Bromocresol Purple is 5',5''-dibromo-o-cresol-sulfonephthalein. The acid form of Bromocresol Purple dye has a dark purple color while the base form has a bright yellow color. Vesicles formed in the solution and were observed under a microscope. The microscope was a Zeiss TM "Axioskop" optical microscope with Differential Interference Contrast optics. The microscope was equipped for photography of images and for real-time on-screen television viewing including video recording capability. The microscope is capable of detecting vesicles down to about 200 nanometers in size when equipped with a 100X oil-immersion lens at a 1250X total magnification. The vesicles were observed with the microscope and a purple color was seen both on the outside and on the inside of the vesicles. When a sodium hydroxide solution was injected into the sample, an instantaneous color change was observed. The diffusion of sodium hydroxide was tracked by observing a yellow color front. When the yellow color front contacted a vesicle and surrounded it, the purple color on the inside of the vesicle remained for one to two minutes and slowly turned to yellow. This indicated that the vesicle formed from the siloxane surfactant acted as a barrier to the diffusion of sodium hydroxide and that Bromocresol Purple was trapped within the vesicle. It further indicated that the rate of diffusion of sodium hydroxide across the vesicle was rapid.

Claims: A method of entrapping a water-soluble substance in a vesicle formed from a siloxane surfactant comprising forming a mixture by dissolving the substance to be entrapped in water, adding a siloxane surfactant, mixing the water solution and the siloxane surfactant and removing excess of the water and the substance from the mixture, the siloxane surfactant being an organosilicon compound having a formula selected from: wherein Me is the methyl group; R is a radical selected from methyl, -(CH 2 ) x O(C 2 H 4 O) y (C 3 H 6 O) z R' and -(CH 2 ) x N + R 3 ''A - , with the proviso that at least one R radical in the molecule cannot be methyl group; R' is selected from hydrogen, a methyl group and an acyl group; R'' is selected from alkyl groups having from one to six carbon atoms, a phenyl group, a benzyl group and the group -CH 2 CH 2 OH; A - is a counterion selected from chloride, bromide, iodide, cyanide, a methyl sulfate group, a salicylate group and a dodecylsulfate group; a has a value of 0 to 200; b has a value of 0 to 50; with the proviso that a and b cannot each be zero; x has a value of 3 to 6; y has a value of 4 to 30; and z has a value of 0 to 5. A method of entrapping a water-insoluble substance in a vesicle formed from a siloxane surfactant comprising dissolving the substance to be entrapped in a siloxane surfactant and mixing the the substance and the siloxane surfactant, the siloxane surfactant being an organosilicon compound having a formula selected from: wherein Me is the methyl group; R is a radical selected from methyl, -(CH 2 ) x O(C 2 H 4 O) y (C 3 H 6 O) z R' and -(CH 2 ) x N + R 3 ''A - , with the proviso that at least one R radical in the molecule cannot be methyl; R' is selected from hydrogen, a methyl group and an acyl group; R'' is selected from alkyl groups having from one to six carbon atoms, a phenyl group, a benzyl group and the group -CH 2 CH 2 OH; A - is a counterion selected from chloride, bromide, iodide, cyanide, a methyl sulfate group, a salicylate group and a dodecylsulfate group; a has a value of 0 to 200; b has a value of 0 to 50; with the proviso that a and b cannot each be zero; x has a value of 3 to 6; y has a value of 4 to 30; and z has a value of 0 to 5. A method according to claim 1 in which the water-soluble substance is selected from salicylic acid; Vitamin C; water-soluble deodorant substances; sodium stearate-based antiperspirant salts; water-soluble preservatives; water-soluble sunscreens; glycerine; enzymes; glycolic acid; water; VIOLET No. 2 and water-soluble drugs. A method according to claims 1 or 2 in which the siloxane surfactant is a compound having a formula selected from: R-[Si(Me) 2 O] 14 -Si(Me) 2 -R in which R is -(CH 2 ) 3 (OCH 2 CH 2 ) 7 OH, R-[Si(Me) 2 O] 14 -Si(Me) 2 -R in which R is -(CH 2 ) 3 (OCH 2 CH 2 ) 12 OH, Me 3 SiO[Si(Me) 2 O] 22 -[SiMeRO] 2 -SiMe 3 in which R is -(CH 2 ) 3 (OCH 2 CH 2 ) 12 OH and Me 3 SiO[Si(Me) 2 O] 103 -[SiMeRO] 10 -SiMe 3 in which R is -(CH 2 ) 3 (OCH 2 CH 2 ) 12 OH and Me is methyl. A method according to claim 2 in which the water-insoluble substance is selected from Vitamin A; water-insoluble preservatives; water-insoluble sunscreens; water-insoluble drugs; pigment dispersions; and polydimethylsiloxane fluids.

Inventors: HILL RANDALL MYRON, SNOW STEVEN ASHLEY, HILL, RANDALL MYRON, SNOW, STEVEN ASHLEY
Applicants: DOW CORNING, DOW CORNING CORPORATION
Application year: 1995
Main classification: A61K9
IPC codes: B01J13, A61Q17, C08L83, A61K8, A61K47, B01F17, A61K9