Nanogel comprising bioactive molecules, therapeutic molecules or drugs together with an amphiphilic molecule

A method of making a nanogel comprising one or more bioactive molecule, therapeutic molecule or drug, together with an amphiphilic molecule, wherein the nanogel is obtained by one of both following methods, depending whether each bioactive molecule, therapeutic molecule or drug is to be loaded separately or simultaneously with the amphiphilic molecule in the nanogel:

• a) when each bioactive molecule, therapeutic molecule or drug is loaded separately with the amphiphilic molecule,
• the method comprises the following in-sequence steps:
• i) mixing poly(methacrylamide)-bearing quinone groups of formula (1)
• wherein x is an integer >1, preferably x is between 1 and 100
• and/or a poly(vinylquinone) represented by formula (6),
• wherein n is an integer >1, preferably n is between 1 and 100;
• with only one bioactive molecule, therapeutic molecule or drug together with an amphiphilic molecule;
• ii) adding a solution of polymer bearing primary or secondary amine groups to the resulting mixture obtained in step i) to generate a crosslinked nanogel comprising one bioactive molecule, therapeutic molecule or drug together with an amphiphilic molecule;
• iii) repeating step 1) and ii) for each additional bioactive molecule, therapeutic molecule or drug;
• iv) mixing each crosslinked nanogel obtained at step iii) to obtain a resulting nanogel comprising two or more biological molecules, therapeutic molecules or drugs together with an amphiphilic molecule.
• b) when the bioactive molecules, therapeutic molecules or drugs are loaded simultaneously with the amphiphilic molecule;
• the method comprises the following in-sequence steps:
• i) mixing poly(methacrylamide)-bearing quinone groups of formula (1)
• wherein x is an integer >1, preferably x is between 1 and 100
• and/or a poly(vinylquinone) represented by formula (6)
• wherein n is an integer >1, preferably n is between 1 and 100;
• with a one or more bioactive molecule, therapeutic molecule or drug together with an amphiphilic molecule;
• ii) adding a solution of polymer bearing primary or secondary amine groups to the resulting mixture of step i) to generate a nanogel comprising one or more bioactive molecule, therapeutic molecule or drug together with the amphiphilic molecule.

A method of producing a medical device, a biomaterial implant or a bioprosthesis with a nanogel coated surface comprising one or more bioactive molecule, therapeutic molecule or drug together with an amphiphilic molecule;

• comprising the following-in-sequence steps of:
• ci) optionally dipping the surface to be coated in a buffer solution of dopamine;
• cii) dipping the surface coated at step ci) into a solution of polymer bearing primary or secondary amine groups;
• then
• ciii) dipping the resulting coated surface obtained at step cii) into a liquid suspension of crosslinked-nanogel comprising one or more bioactive molecule, therapeutic molecule or drug together with the amphiphilic molecule;
• then
• civ) drying the crosslinked coated surface obtained at step (ciii) to obtain a coated crosslinked-nanogel surface comprising one or more bioactive molecule, therapeutic molecule or drug together with the amphiphilic molecule;
• cv) optionally repeating steps cii) to civ) to obtain a surface coated with several layers of crosslinked nanogels comprising one or more bioactive molecule, therapeutic molecule or drug together with the amphiphilic molecule.

A method of producing a medical device, a biomaterial implant or a bioprosthesis with a coated surface, wherein the coating is obtained by the following in-sequence steps:

• i) optionally dipping the surface to be coated in a buffer solution of dopamine;
• ii) dipping the surface coated with dopamine at step i);
• in a solution of polymer bearing primary or secondary amine groups;
• then
• iii) dipping the resulting coated surface obtained at step ii) in a mixture of a poly(methacrylamide)-bearing quinone groups of formula (1)
• wherein x is an integer >1, preferably x is between 1 and 100
• and/or of a poly(vinylquinone) of formula (6)
• wherein n is an integer >1, preferably n is between 1 and 100;
• with one or more bioactive molecule, therapeutic molecule or drug together with an amphiphilic molecule;
• iv) drying the crosslinked coated surface obtained at step iii) to obtain a coated crosslinked monolayer surface comprising one or more bioactive molecule, therapeutic molecule or drug together with the amphiphilic molecule;
• v) optionally repeating steps ii) to iv) to obtain a surface coated with several layers of crosslinked multilayers comprising one or more bioactive molecule, therapeutic molecule or drug together with the amphiphilic molecule, preferably the vitamin-E derivative.