Devices, methods, and compositions for thermal acceleration and drug delivery
View Patent ↗A thermal accelerant can be used as a drug delivery vehicle to deliver one or more drugs to a target site. For example, in some embodiments, a carrier such as albumin or human serum albumin (HSA) can be impregnated with, or covalently attached to, an anti-tumor agent and delivered to a location proximate to a tumor of a patient. The carrier can be exposed to an energy source that structurally alters the carrier and releases the agent therefrom. The sources of energy can include one or more of microwave, radiofrequency, electrical pulse (electroporation) or sonar (HIFU or histotripsy). In some embodiments, the anti-tumor agent can be delayed release such that a portion of the agent is released from the carrier over an extended period of time. The incorporation of an anti-tumor agent in a thermal accelerant provides a thermal ablation-drug delivery combination therapy (e.g., a thermally-activated combination therapy).
1 . A drug delivery composition comprising:
a carrier that includes a polymer configured to coagulate when exposed to prescribed energy from an energy source to become relatively immobilized after being positioned within a target site;
a chaotrope configured to adjust the charge distribution within the carrier; and
a drug configured to be associated with the carrier, the drug being configured to be released following exposure of the prescribed energy from the energy source,
wherein the carrier is configured to be structurally altered upon exposure to the prescribed energy from the energy source to release the drug.
2 . The composition of claim 1 , wherein the drug is configured such that a portion of the drug is released from the carrier over at least 48 hours.
3 . The composition of claim 1 , wherein a concentration of the carrier can range from approximately 30 mg/mL to approximately 600 mg/mL.
4 . The composition of claim 1 , wherein the drug is associated with the carrier by at least one of protein binding or covalent bonding.
5 . The composition of claim 1 , wherein the polymer comprises albumin or structurally modified albumin.
6 . The composition of claim 1 , wherein structurally altered comprises denaturation of the carrier.
7 . The composition of claim 6 , wherein denaturation of the carrier alters at least one of:
a protein binding percentage between the drug and the carrier; or a shape of the carrier.
8 . The composition of claim 1 , wherein the energy source includes one or more of microwave, radiofrequency, electrical pulse or sonar.
9 . The composition of claim 1 , wherein the drug includes one or more of PD-1 Pembrolizumab, Nivolumab, Cemiplimab, PD-L1 Atezolizumab, Avelumab, Durvalumab (Imfinzi) and CTLA4 Ipilimumab siRNA, peptides, proteins, immunogens, RNA, mRNA, DNA, or nucleoside analog-based agents.
10 . The composition of claim 1 , wherein the drug includes one or more of kinase inhibitors, or doxorubicin, taxol, or other non-kinase anti-tumor agents.
11 . The composition of claim 1 , wherein the polymer comprises one or more of DNA, RNA, glycoproteins or glycopolymers such as IgA, IgG, or other immunoglobulins.
12 . The composition of claim 1 , wherein the drug comprises a drug for targeting macrophages in cancer immunotherapy comprises one or more of: CSF1; CCL2; CCR2; SIRPa; TIE 2; Arginase; HER2; GC vitamin D-binding protein; CD40; BTK; CSF IR; or CD47.
13 . The composition of claim 1 , wherein the drug comprises a drug for targeting cGAS-STING-TBK1 signaling pathway with at least one or more of ADU-SIO0, MK-1454, MK-2118, BMS-986301, GSK3745417, SB-11285, orIMSA-101.
14 . The composition of claim 1 , wherein the drug comprises a drug for cancer vaccines TLR and STING agonists: target RIG-I/MDAS and TLR3; TLR4; TLR7/8; TLR9; STING FLT3L and CD40 agonists: target rhFLT3L; Agonistic anti-CD40 antibody.
15 . A thermally-activated combined treatment composition, comprising:
a therapeutic agent; and
a thermal accelerant configured to:
enhance ablation treatment;
be impregnated with the therapeutic agent; and
elute the therapeutic agent after exposure to energy from an energy source, wherein:
the combined treatment composition is thermally activated by exposure to energy from an energy source; and
after the thermal accelerant is exposed to the energy from the energy source:
the thermal accelerant is configured to become coagulated and becomes coupled with the ablated tissue; and
the thermal accelerant is configured to begin to elute a portion of therapeutic agent.
16 . The composition of claim 15 , wherein the therapeutic agent is associated with the thermal accelerant by at least one of protein binding or covalent bonding.
17 . A thermally-activated combined treatment composition, comprising:
a therapeutic agent; and
a thermal accelerant configured to:
enhance ablation treatment;
be impregnated with the therapeutic agent; and
elute the therapeutic agent after exposure to energy from an energy source, wherein:
the combined treatment composition is thermally activated by exposure to energy from an energy source; and
the thermal accelerant comprises:
a carrier comprising an albumin;
an ionic component comprising at least one chaotrope; and
an imaging component.
18 . The composition of claim 17 , wherein:
the albumin comprises human serum albumin or bovine serum albumin;
the chaotrope comprises at least one of calcium chloride, cesium chloride, lithium chloride, potassium chloride, rubidium chloride, sodium chloride, sodium citrate, trisodium citrate, sodium tryptophanate, citric acid, octanoic acid, or a combination thereof; and
the imaging component comprises at least one of NaCl, CsCl, or albumin.
19 . The composition of claim 18 , wherein, when the thermal accelerant is exposed to
the energy source;
the energy source is configured to begin to denature the albumin; and
the denatured albumin is configured to:
become coagulated; and
release the impregnated drug.