Polymerizable lipids for preparing vesicles that controllably release an encapsulant

• US 5,366,881 A
• Filed: 02/23/1993
• Issued: 11/22/1994
• Est. Priority Date: 02/23/1993
• Status: Expired due to Fees

• Current Assignee: The United States of America As Represented By The Secretary of Agriculture
• Original Assignee: the united states of america as represented by the secretary of the navy
• Inventors: Singh, Alok, Schnur, Joel M.
• Primary Examiner(s): Naff, David M.
• Application Number:
  US08/023,834
• Time in Patent Office: 637 Days
• Field of Search: 435/4, 435/174, 435/177, 435/180, 435/182, 435/968, 435/262.5, 436/535, 424/94.1, 424/408, 424/417, 424/450, 554/1, 264/4, 264/4.1, 512/4, 252/174.11, 252/174.12, 252/DIG. 12
• US Class Current: 435/177
• CPC Class Codes: A61K 8/14 Liposomes; Vesicles
• CPC Class Codes: A61K 9/1273 Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances polymers grafted or coated on phosphatidyl liposomes A61K9/1271, on non-phosphatidyl liposomes A61K9/1272
• CPC Class Codes: A61Q 13/00 Formulations or additives for perfume preparations essential oils or perfumes per se C11B9/00
• CPC Class Codes: C12N 11/04 entrapped within the carrier, e.g. gel or hollow fibres
• CPC Class Codes: Y10S 435/968 High energy substrates, e.g. fluorescent, chemiluminescent, radioactive

Abstract

The present invention provides novel polymerizable lipids and mixtures thof with non-polymerizable lipids and methods for the controlled release of encapsulated materials using stabilized or polymerized vesicles. Release is induced by pH, ions, temperature, light or other changes in the environment. Time release mechanisms are also employed. Applications of the present invention especially include encapsulation of enzymes and their subsequent sustained release for degradation of environmental pollutants, encapsulation of fluorescent markers for use in sensor systems, and encapsulation and release of fragrant molecules in detergents.

Claims

1. A polymerizable lipid having the following structure:

##STR6## where n is 1-10 and m is 15-n; and

each R is individually selected from the group consisting of;

space="preserve" listing-type="equation">--O--CH.sub.2 --CH═

CH--CH═

CH--CH.sub.3,

space="preserve" listing-type="equation">--OCH.sub.2 CH═

CH.sub.2,

space="preserve" listing-type="equation">--OC(═

O)--C(CH.sub.3)═

CH.sub.2

and

space="preserve" listing-type="equation">--OC(═

O)--CH═

CH--CH═

CH--CH.sub.3.

2. The lipid of claim 1 wherein n is 2-6.

3. A mixture of polymerizable lipid and up to about 90 mole percent of non-polymerizable lipid, said polymerizable lipid having the following structure:

##STR7## where n is 1-10 and m is 15-n; and

each R is individually selected from the group consisting of;

space="preserve" listing-type="equation">--O--CH.sub.2 --CH═

CH--CH═

CH--CH.sub.3,

space="preserve" listing-type="equation">--OCH.sub.2 CH═

CH.sub.2,

space="preserve" listing-type="equation">--OC(═

O)--C(CH.sub.3)═

CH.sub.2

and

space="preserve" listing-type="equation">--OC(═

O)--CH═

CH--CH═

CH--CH.sub.3.

4. The mixture of claim 3 wherein said non-polymerizable lipid is selected from the group consisting of phosphatidylserines, phosphatidylethanolamines, saturated phosphatidylcholines containing at least one diazobenzene moiety, and mixtures thereof.

5. The mixture of claim 4 wherein amount of said non-polymerizable lipid is up to about 80 mole percent.

6. Polymerized vesicles comprising polymerizable lipid or a mixture of polymerizable lipid and up to 90 mole percent of non-polymerizable lipid, said polymerizable lipid having the following structure:

##STR8## where n is 1-10 and m is 15-n;

each R is individually selected from the group consisting of;

space="preserve" listing-type="equation">--O--CH.sub.2 --CH═

CH--CH═

CH--CH.sub.3,

space="preserve" listing-type="equation">--OCH.sub.2 CH═

CH.sub.2,

space="preserve" listing-type="equation">--OC(═

O)--C(CH.sub.3)═

CH.sub.2

and

space="preserve" listing-type="equation">--OC(═

O)--CH═

CH--CH═

CH--CH.sub.3 ;

and said non-polymerizable lipid being selected from the group consisting of ammonium surfactants, phosphate surfactants, and saturated phosphatidylcholines.

7. The polymerized vesicles of claim 6 wherein n is 2-6.

8. The polymerized vesicles of claim 6 including an encapsulant selected from the group consisting of antioxidizing agents, antibacterial agents, antifungal agents, DNA, enzymes, fragrances, fluorescent markers, and mixtures thereof, said encapsulant being in an amount of 1-500% by weight of said vesicles.

9. The polymerized vesicles of claim 8 wherein amount of said encapsulant is 20-200% by weight.

10. The polymerized vesicles of claim 6 including a fragrance encapsulant in an amount of 1-500% by weight, based in the weight of said vesicles.

11. The polymerized vesicles of claim 10 wherein the fragrance encapsulant is lipophilic and is in an amount of 20-200% by weight.

12. A method of encapsulating an encapsulant in vesicles and releasing the encapsulant from the vesicles comprising the steps of:

forming vesicles from at least one lipid selected from the group consisting of polymerizable lipid and mixtures of polymerizable lipid and up to 90 mole percent of non-polymerizable lipid, based on said polymerizable lipid and said non-polymerizable lipid, said polymerizable lipid having the following structure;

##STR9## where n is 1-10 and m is 15-n;

each R is individually selected from the group consisting of;

space="preserve" listing-type="equation">--O--CH.sub.2 --CH═

CH--CH═

CH--CH.sub.3,

space="preserve" listing-type="equation">--OCH.sub.2 CH═

CH.sub.2,

space="preserve" listing-type="equation">--OC(═

O)--C(CH.sub.3)═

CH.sub.2

and

space="preserve" listing-type="equation">--OC(═

O)--CH═

CH--CH═

CH--CH.sub.3 ;

said non-polymerizable lipid being selected from the group consisting of ammonium surfactants, phosphate surfactants, and saturated phosphatidylcholines;

encapsulating at least one encapsulant in the vesicles in an amount of about 20-200 by weight, based on the weight of said vesicles; and

subjecting the vesicles to an environmental change which causes the vesicles to release the encapsulant.

13. The method of claim 12 wherein a portion of the encapsulant is disposed on an outside surface of the vesicles and wherein the non-polymerizable lipid is selected from the group consisting of phosphatidylserines, phosphatidylethanolamines, saturated phosphatidylcholines containing at least one diazobenzene moiety, and mixtures thereof.

14. The method of claim 13 wherein the amount of said non-polymerizable lipid is up to about 80 mole percent and said method includes a step of removing said encapsulant from the outside surface of said vesicles.

15. The method of claim 12 wherein said encapsulant is selected from the group consisting of antioxidizing agents, antibacterial agents, antifungal agents, DNA, enzymes, fragrances, fluorescent markers, and mixtures thereof in an amount of 1-500% by weight of said vesicles;

and wherein said saturated phosphatidylcholines contain at least one diazobenzene moiety synthesized from a precursor acid having the following structure;

space="preserve" listing-type="equation">CH.sub.3 --(CH.sub.2).sub.11 --O--BzN═

N--Bz--O--(CH.sub.2).sub.10 --COOH where Bz═

benzene.

16. The method of claim 15 wherein said environmental change is selected from the group consisting of changes in temperature, pH, light and ion concentration.

17. The method of claim 16 wherein said fragrance is lipophilic.

18. The method of claim 16 wherein said fluorescent marker is a fluorescent dye.