the invention is illustrated by the following examples that are not construed to limit the invention in any way : under a nitrogen blanket , 3 g ( 4 . 7 mmol ) of calix [ 6 ] arene , 7 . 2 g ( 7 val ) of dodecanoyl chloride and 6 . 3 g ( 10 val ) of anhydrous aluminum chloride are added under anhydrous conditions to 200 ml of dry nitrobenzene . the deep orange solution is stirred during 20 hours at room temperature . the reaction is then quenched by poring the reaction mixture on 1 kg of ice . the reaction product is extracted with chloroform , washed successively with 500 ml 1m hydrochloric acid , 2 , 500 ml of 1m nacl solution , and 2 , 500 ml of deionized water . the organic phase is dried on magnesium sulfate , and the solvent is evaporated in vacuo until a final volume of 50 ml . the brownish orange residue is added to 500 ml of methanol , and the fine precipitate is filtered off and dried in vacuo . the white powder thus obtained is analyzed by nmr , and the structure of hexa - p - dodecanoyl - calix [ 6 ] arene is ascertained . yield : 50 %. in modifying the amounts of the calixarene component , and by using the same reaction conditions and working techniques , other p - dodecanoyl - calixarenes and other p - acyl - calixarenes have been obtained in yields between 50 and 85 %. this example illustrates the typical working technique for the manufacture of the compositions of this invention . the preparation of calixarenes modified by coupling a 12 carbon atom acyl chain in the para position to phenolic hydroxyl function is for example described in shahgaldian et al . ( loc . cit .) see also example a above . tetra - p - dodecanoyl - calix [ 4 ] arene is dissolved in a suitable solvent , in the case of this example tetrahydrofuran , to generate phase ( 2 ) ( 3 ml ). phase ( 2 ) is added to an aqueous phase is ( 3 ) ( 100 ml ) under magnetic stirring . the medium immediately becomes opalescent by formation of modified calix [ 4 ] arene nanosphere . the average size of the nanospheres , measured by a laser - beam diffractometer ( 4700c from malvern ), is 150 nm with an average dispersion index of 0 . 1 . the suspension may be concentrated under reduced pressure to the desired volume , for example 10 ml or thereabouts . the appearance of the nanosphere suspension remains unchanged after standing for a prolonged period ( 12 months ) and there is no sign , in particular , either of irreversible sedimentation or of variation in the size of the nanospheres . the method is carried out as in example 1 , but by adding the aqueous phase ( 3 ) to the tetrahydrofuran phase ( 2 ). the nanosphere dispersion obtained has the same characteristics as those described in example 1 . the method is carried out as in example 1 , but by adding the tetrahydrofuran phase ( 0 . 5 ml ) to the aqueous phase ( 10 ml ) without stirring the medium . the nanospheres obtained are 145 nm in size and have an average dispersion index of 0 . 11 . the method is carried out as in example 1 , but with addition of a surface - active agent ( tween , 0 . 1 - 1 %, v / v ) to the aqueous phase . the nanospheres obtained are 150 mn in size and have an average dispersion index of 0 . 3 . the method is carried out as in example 1 , and the obtained suspension of nanospheres is then sterilized in an autoclave at 120 ° c . for 15 minutes . the average particle size remains essentially unchanged after sterilization . the method is carried out as in example 1 , and the suspension is then freeze - dried . the addition of a cryoprotector ( maltose , trehalose and the like ) is not essential . the average particle size measured immediately after freeze - drying remains unchanged . the method is carried out as in example 1 , replacing 12 - carbon acyl chain modified calix [ 4 ] arene by para - galactosyl - o - 5 - carbon modified calix [ 4 ] arene . the average size of the nanospheres is 110 nm with an average dispersion index of 0 . 1 . these nanospheres may be sterilized in the autoclave and freeze - dried as for those cited in example 1 . the method is carried out as in example 1 , replacing the respective calix [ 4 ] arene derivative with a calix [ 6 ] arene derivative containing 6 phenolic units . the average size of the nano - spheres formed is 145 nm with a high polydispersity index of 0 . 21 . the method is carried out as in example 1 , replacing the respective calix [ 4 ] arene derivative with a calix [ 8 ] arene derivative containing 8 phenolic units . under these conditions stable nanospheres were also obtained . preparation of mixed 12 - carbon acyl chain modified calix [ n ] arene nanospheres , where n = 4 , 6 and 8 the method is carried out as in example 1 , replacing the respective calix [ 4 ] arene derivative with a mixture of 12 - carbon acyl chain modified calix [ n ] arenes , in the proportions 1 : 1 for binary mixtures and 1 : 1 : 1 and 1 : 1 : 2 for tertiary mixtures . the method is carried out as indicated in example 1 . after concentration of the suspension of modified - calix [ 4 ] arene nanospheres to a volume of 10 ml , increasing quantities of sodium chloride are added thereto . the nanosphere suspension is perfectly stable when the sodium chloride concentration corresponds to physiological ionic strength ( 0 . 154 m ) and stability remains at concentrations up to one order of magnitude greater than physiological ionic strength . stability of the calix [ n ] arene nanospheres in the presence of an acidic or basic medium the method is carried out as indicated in example 1 . after concentration of the suspension of calixarene nanospheres to a volume of 10 ml ., increasing quantities of hydrochloric acid ( 1 mole per liter ) or of sodium hydroxide ( 1 mole per liter ) are added progressively to the medium . the nanosphere suspension is perfectly stable , under ph values ranging from 1 to 12 . the method is carried out as indicated in example 1 . after concentration of the suspension of calix [ n ] arene nano spheres to a volume of 30 ml , three batches of 10 ml each are prepared . the batches are placed at 3 ° c ., 20 ° c . and 40 ° c ., respectively . the suspensions remain stable over time and do not exhibit , after storage for a minimum of 12 months , either irreversible sedimentation or variation in the size of the nanospheres . the method is carried out as indicated in example 1 , in this case a 0 . 154 mole / liter solution of sodium chloride is used as phase ( 3 ). the nanospheres prepared under physiological ionic strength have a size of 160 nm with a dispersion index of 0 . 15 nm . the suspension remains stable over time and does not exhibit , after storage for 12 months , either irreversible sedimentation or variation in the size of the nanoparticles . the method is carried out as in example 1 , but the calix [ n ] arene is dissolved in an tetrahydrofuran / water mixture ( 90 / 10 , v / v ) instead of pure tetrahydrofuran . the presence of a low proportion of non - solvent for the calix [ n ] arene in a solvent gives the nanospheres that are obtained , an average size of 160 nm with an average dispersion index of 0 . 11 . the method is carried out as in example 1 . after concentration of the suspension of calixarene nanospheres to a volume of 30 ml ; the resulting suspension of calix [ n ] arene nanospheres is treated with ultra - violet irradiation ( 254 nm ) for 12 hours , the size of the nanospheres after irradiation is 160 mn with an average dispersion index of 0 . 15 . the suspension remains stable over time and does not exhibit , after storage for 12 months , either irreversible sedimentation or variation in the size of the nanospheres . the method is carried out as in example 1 , but 5 mg of β - carotene are added to the solvent phase ( 2 ). the nanospheres obtained have an average size of 145 nm with a dispersion index of 0 . 12 . analysis by visible spectroscopy shows & gt ; 70 % incorporation of β - carotene . there is no degradation of the β - carotene over a period of storage exceeding 6 months . the method is carried out as in example 1 , but 10 mg of menthol are added to the organic phase . the nanospheres obtained have an average size of 100 nm and an average dispersion index of 0 . 14 . the method is carried out as in example 1 , but 10 mg of an amino acid , for example alanine , are added to the aqueous phase . the nanospheres obtained have an average size of 130 nm and an average dispersion index of 0 . 12 . preparation of an aqueous gel phase a water 84 . 5 % carbomer 0 . 5 % propylene glycol 15 . 0 % phase b calixarene nanospheres 0 . 01 % to 10 % phase a is prepared by heating all constituents to 80 ° c ., whereupon the mixture is homogenous . phase b is added under vigorous stirring . the gel is forming while the mixture is cooling . the size of the nanospheres is not measured due to the viscosity of the resultant gel . however no visual sedimentation is observed after two months of storage at 4 ° c ., 20 ° c . and 40 ° c . the calix [ n ] arene based nanospheres described in this invention may be applied in a wide variety of applications , as described above . the nanospheres of this inventions may thus be used , for example , for the following purposes : as modifiers of the kinetics of release of agents , such as retinal , for dermal treatment , as agents for the stabilization of sensitive molecules , such as ,- carotene , to increase shelf life of cosmetic products , as agents to modify the aroma properties of cosmetic products , as modulators of surfactant properties of emulsifiers used in cosmetic products , as modulator of dermal penetration of active molecules , as dispersion agents for cosmetic products used in solar skin creams as modifiers of the pharmacokinetics of the release of active compounds such as cis - platin for the treatment of cancer , as agents for the stabilization of sensitive molecules such as fatty esters sensitive to lipases , in order to increase the biostability of pharmaceutical products , as agents for modifying the taste of orally administered medications , as modulators to decrease the amount of flavoring agents used in cooling processes , as stabilizers to increase the life time of molecules sensitive to oxidation used in the food industry , as controlled release systems for the liberation of orally administered medications at the ph of the stomach , as carriers for the selective transportation of medicines to predetermined biological sites , as controlled release agents for pheromones for “ green ” insecticide treatments . their use in other fields will allow to obtain similar effects . for example , the nanoparticles are miscible with lipoproteins . the plasmic membrane of living cells is an essential constituent of the structural integrity of cells . this membrane comprises lipids and proteins and acts not only as a physical barrier to separate different compartments but also as a substrate for a great number of reactions that occur in its interior . these membrane shaped lipids are amphiphilic molecules . this affinity ambivalence provides the capability of adsorption to interfaces and the self - assembly capability in aqueous media . the above - described nanoparticle forming calixarene derivatives , i . e . upper crown long - chain fatty acid acylated and lower crown selective phosphorylated calixarenes , especially the calix [ 4 ] arenes , show a high tendency to crystallize whereas natural phospholipids have only a low crystallizing ability . during our work , numerous crystals of the substituted calixarenes have been obtained . the studies of langmuir monomolecular layers have shown that our synthetic calixarenes , substituted as described above , a greatly miscible with natural phospholipids ( dppa and dppc ). the self - assemblies which are forming in water have been studied as to light diffusion dynamics and atomic force microscopy . the results show that these supramolecular assemblies are different from structures that are generally formed by lipids ; in fact , the new structures are neither micelles nor liposomes ( g . gregoriadis , b . e . ryman , liposomes as carriers of enzymes or drugs , biochem . j . 124 ( 1971 ), 58p ) but nanoparticles . these nanoparticles distinguish from the above - mentioned other structures by their great mechanical resistance and their long - life stability . the new structures of this invention may therefore also be used for the solubilization of membrane proteins and for the reconstitution of bioinimetic systems where the process of crystal nucleation is favored .
a water dispersible colloidal system in the form of generally spherical matrix type particles and of sizes typically in the range of from 50 to 500 nm , called nanoparticles , and a process for the preparation of such systems . the system is characterized in that the nanoparticles comprise at least one amphiphilically modified calixarene . the water dispersion contains at least one active component such as a cosmetic , a pharmaceutical compound or other biologically active substances , foods , beverages , etc . enclosed within the nanoparticles , in the outer aqueous phase , or in both . the systems show outstanding properties , especially long - life stability even at elevated la temperatures .