Cross-linked collagen comprising metallic anticancer agents
View Patent ↗The disclosure describes collagen constructs comprising anticancer agents, preferably, platinum, and related methods.
1. A method of manufacturing a therapeutically effective anticancer cross-linked collagen construct comprising cross-linked collagen and an amount of a releasable platinum-containing anticancer agent, wherein said cross-linked collagen comprises collagen and one or more cross-linking agents which cross-link the collagen in said construct, wherein the platinum is incorporated into the construct by chelation to said agents, and wherein the platinum is capable of being released in vivo when administered to a subject, the method comprising contacting the cross-linked collagen with a cis-diaqua or a cis-dihalo platinum complex to provide the therapeutically effective anticancer cross-linked collagen construct.
2. A method of treating a subject suffering from cancer amenable to treatment with platinum alkylators, the method comprising administering a therapeutically effective amount of an anticancer cross-linked collagen construct to the subject, wherein the construct comprises (a) cross-linked collagen comprising collagen and one or more cross-linking agents which cross link the collagen in said construct and (b) an anticancer amount of a releasable platinum-containing anticancer agent incorporated into the construct, wherein at least a portion of the platinum incorporated into the construct is incorporated by chelation to said agents, and wherein the platinum is capable of being released in vivo when administered to the subject.
3. The method of claim 2 , wherein the anticancer cross-linked collagen construct provides plurality of in vivo release rates.
4. The method of claim 2 wherein the anticancer cross-linked collagen construct provides a sustained release of platinum, wherein the sustained release comprises a plurality of release rates comprising an immediate release, an intermediate release, an extended release or any combination of release rates thereof.
5. The method of claim 1 wherein at least one of the cross-linking agents comprises a 1,2-benzoquinone and/or a 1,2-dihydroxy phenyl moiety.
6. The method of claim 1 where the platinum is chelated at least in part to the benzoquinone and/or the 1,2-dihydroxyphenyl moiety.
7. The method of claim 2 wherein at least one of the cross-linking agents comprises a 1,2-benzoquinone and/or a 1,2-dihydroxy phenyl moiety.
8. The method of claim 2 where the platinum is chelated at least in part to the benzoquinone and/or 1,2-dihydroxyphenyl moiety.