Polymer implants for treatment of metabolic disorders
Implantable devices including a biocompatible matrix configured for long term location in adipose tissue and a biologically active agent that can be carried by the matrix and delivered to the adipose tissue following implant therein. The biologically active agent can include a modulator or a precursor thereof that can directly or indirectly modify the gene expression of adipose cells, e.g., adipocytes, and thereby modify the presence or quantity of one or more expression products of the adipose tissue that may act locally on distant from the implant site in an endocrine fashion. Modulators can include small molecules (e.g., resveratrol), polynucleotides (e.g., RNAi), or polypeptides (e.g., antibodies or functional fragments thereof).
1. An implantable device comprising:
a biocompatible matrix comprising a poly(lactide-co-glycolide) copolymer; and
an adipose tissue expression product modulator encapsulated within or bonded to the biocompatible matrix, the adipose tissue expression product modulator comprising resveratrol (3,5,4′-trihydroxy-tans-stilbene), butein (3,4,2′,4′-tetrahydroxychalcone); piceatannol (3,5,3′,4′-tetrahydroxy-trans-stilbene); isoliquiritigenin (4,2′,4′-trihydroxychalcone); fisetin (3,7,3′,4′-tetrahydroxyflavone); or quercetin (3,5,7,3′,4′-pentahydroxyflavone); wherein
the implantable device is configured for implant into adipose tissue and the biocompatible matrix is configured to release the adipose tissue expression product modulator into the adipose tissue over time wherein the biocompatible matrix comprises polymer particles comprising the poly(lactide-co-glycolide) copolymer and the adipose tissue expression product modulator encapsulated within the polymer particles, further comprising additional polymer particles that do not encapsulate the adipose tissue expression product modulator.
2. The implantable device of claim 1 , wherein the biocompatible matrix is biodegradable.
3. The implantable device of claim 1 , wherein the biocompatible matrix is porous.
4. The implantable device of claim 1 , wherein the adipose tissue expression product modulator comprises resveratrol (3,5,4′-trihydroxy-tans-stilbene).
5. The implantable device of claim 1 , wherein the device is configured for implant into visceral adipose tissue.
6. The implantable device of claim 1 , comprising the adipose tissue expression product modulator in an amount of from about 4 wt. % to about 40 wt. % by weight of the biocompatible matrix.