Cross-linked collagen comprising metallic anticancer agents
View Patent ↗The disclosure describes collagen constructs comprising anticancer agents, preferably, platinum, and related methods.
1. An anticancer cross-linked collagen construct comprising:
a cross-linked collagen comprising collagen and one or more entities which cross link collagen in said construct and
an anticancer amount of platinum incorporated into the construct, wherein at least a portion of the platinum incorporated into the construct is incorporated by chelation to said entities.
2. The construct of claim 1 , wherein at least one of the cross-linking entities comprises a 1,2-benzoquinone and/or a 1,2-dihydroxy phenyl moiety.
3. The construct of claim 1 , where the platinum is chelated at least in part to the benzoquinone and/or the 1,2-dihydroxyphenyl moiety.
4. The construct of claim 1 , wherein at least one of the cross-linking entities is selected from the group consisting of entities arising from cross-linking the collagen with nordihydroguaiaretic acid (NDGA), 3,4-dyhydroxyphenylalanine, dopamine, 3,4-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic acid, and tannic acid.
5. The construct of claim 1 , wherein at least one of the cross-linking entities is arising from cross-linking the collagen with NDGA.
6. The construct of claim 1 , wherein the platinum comprises platinum (II) and/or platinum (IV).
7. The construct of claim 6 wherein the platinum comprises cis-(NH 3 ) 2 Pt(II),
8. The construct of claim 1 , wherein the platinum incorporated into the construct is present in an amount of between about 0.1% to about 30%.
9. The construct of claim 1 , wherein some or all of the anticancer amount of platinum is released in vivo in contact with an aqueous medium.
10. The construct of claim 1 , wherein the anticancer cross-linked collagen construct provides a sustained release of platinum, wherein the sustained release comprises a plurality of release rates including an immediate release, an intermediate release, an extended release or any combination of release rates thereof.
11. The construct of claim 10 , wherein an effective amount of platinum is released from about 1 minute to about 60 days, or any range therein.