Controlled-release peptide compositions and uses thereof
Controlled-release formulations of carboxy-terminal C5 a analogs (such as sustained-release formulations of the analogs), and their use in methods for treating and preventing an infection or a disease such as cancer, for directly killing microorganisms, for vaccine preparation, for inducing an immune response and for targeting antigen-presenting cells and other cells bearing a C5 a receptor, are provided.
1. A controlled-release formulation comprising an encapsulating material and a first biologically active agent in the form of an oligopeptide C-terminal C5a analog encapsulated therein, the C5a analog being conjugated to a peptide immunogen, the C5a analog being a C5a receptor agonist having a response-selective C5a receptor binding activity, said binding activity comprising activation of antigen presenting cells, wherein the C5a analog is EP67 bearing the sequence:
(SEQ ID NO: 4)
Tyr-Ser-Phe-Lys-Asp-Met-Pro-MeL-(D-Ala)-Arg.
2. The formulation according to claim 1 , wherein the peptide immunogen is characteristic of a biological entity selected from the group consisting of a diseased cell, an infectious bacterium, an infectious parasite, an infectious fungus, an infectious protozoan, an infectious prion, an infectious virus and a biofilm.
3. The formulation according to claim 2 , wherein the diseased cell is a tumor cell.
4. The formulation according to claim 1 wherein the encapsulating material is selected from the group consisting of a polymer-based nanoparticle, a nanogel, a microparticle, a microgel, a microcapsule, a nanocapsule, a polyelectrolyte capsule, a biodegradable lattice, a polysaccharide capsule, a block co-polymer micelle, a polyelectrolyte complex, an injectable implant, a diffusion-controlled hydrogel and a micro-emulsion.
5. The formulation according to claim 4 wherein the encapsulating material is selected from the group consisting of a poly(lactic-co-glycolic acid) (PLGA), an ethyl cellulose, a polymethyl methacrylate, a polyethylene glycol, a poly-3-hydroxy butyrate, a starch, an alginate, a collagen, a gelatin, a chitin, a chitosan, a zein, a cross-linked albumin, an azo-cross-linked copolymer of styrene and HEMA-coated particle, a hydrogel, a maleic anhydride and poly (N-isopropylacrylamide) hybrid hydrogel, a hydroxyapatite, a hyaluronic acid, a polysebacic anhydride, a polyester, a polylactide, polyorthoester, a polycarbonate, a polycaprolactone, a polyethylene oxide, a lipid and an amino acid.
6. The formulation according to claim 5 wherein the encapsulating material is poly (lactic-co-glycolic acid) (PLGA).
7. The formulation according to claim 1 , wherein the controlled-release formulation is capable of providing a sustained release of the C5a analog upon in vivo administration to a mammal as measured by a longer period of detectable C5a binding activity when the formulation is administered than when the C5a analog alone is administered.
8. The formulation according to claim 1 further comprising a second biologically active agent.