A photoresponsive delivery system based on a modified pamam and methods thereof
AssigneeThe University of Hong Kong
InventorsWeiping WANG, Yang ZHOU, Yafei LI
Life of this patent
Estimating the term…
Abstract
Provided is a system for drug delivery comprising a modified poly (amidoamine) (“PAMAM”) comprising a photo-cleavable compound bound to one or more active agents to form a nanocomplex. Also provided is a method of treating a subject comprising administering the PAMAM nanocomplex and irradiating the nanocomplex at the target site with a light source. In particular, the modified PAMAM is a DEACM-modified PAMAM or a BODIPY-modified PAMAM. Also provided is a method for screening for PAMAM-coumarin-active agent nanocomplexes.
Claims71
A system for drug delivery comprising a modified poly(amidoamine)(“PAMAM”) comprising a photocleavable compound bound to one or more active agents to form a nanocomplex, wherein the photocleavable compound is 7-diethylamino-4-hydroxymethyl-coumarin (“DEACM”).
The system of anyone of the preceding claims wherein the one or more active agents is an enzyme.
The system of anyone of the preceding claims wherein the enzyme is glucose oxidase and caspase-3.
The system of anyone of the preceding claims wherein the one or more active agents is insulin or nimotuzumab.
The system of anyone of the preceding claims wherein the nanocomplex has a diameter of about 20-200 nm, or about 100-170 nm.
A self-assembly system for drug delivery comprising a modified PAMAM conjugated to one or more coumarin derivatives.
The system of anyone of the preceding claims, wherein the coumarin derivative can be selected from formula (I), formula (II), formula (III), formula (IV), formula (V), or formula (VI):
A method of delivering a drug to a subject at a target site comprising:
- (i) providing a PAMAM-DEACM compound that is bound to one or more active agents to form a PAMAM-DEACM active agent nanocomplex;
- (ii) administering the nanocomplex to the subject;
- and (iii) irradiating the nanocomplex at the target site with a light source to release the one or more active agents.
The method of anyone of the preceding claims wherein the light source has a wavelength of 350-700 nm.
The method of anyone of the preceding claims wherein the light source has a wavelength of 420-495 nm.
The method of anyone of the preceding claims wherein the light source has a wavelength of 620-750 nm.
The method of anyone of the preceding claims wherein the nanocomplex releases one or more active agents within 2 minutes of light irradiation at 50 mW/cm2 or other time periods and irradiances.
The method of anyone of the preceding claims wherein the target site is intracellular.
The method of anyone of the preceding claims wherein the target site is the eye or skin.
A method of treating cancer in a subject in need thereof comprising:
- (i) administering a PAMAM-DEACM compound that is bound to glucose oxidase and/or caspase-3 to form a PAMAM-DEACM active agent nanocomplex;
- and (ii) irradiating the nanocomplex at the target site with a light source to release the glucose oxidase and/or caspase-3.
The method of anyone of the preceding claims wherein the light source has a wavelength of 420-495 nm.
A method for screening coumarin derivatives for delivery of one or more active agents comprising:
- (i) providing coumarin derivatives conjugating with PAMAM to form PAMAM-coumarins conjugates;
- (ii) assembling PAMAM-coumarins and the one or more active agents to form a PAMAM-coumarin-active agent nanocomplex;
- (iii) measuring dispersion of the PAMAM-coumarin-active agent nanocomplex using dynamic light scattering (“DLS”);
- (iv) quantifying delivery efficiency of the PAMAM-coumarin-active agent nanocomplex;
- and (v) selecting the PAMAM-coumarin-active agent nanocomplex with the highest delivery efficiency.
The method of anyone of the preceding claims wherein the coumarin derivatives have a high hydrophobicity and not photocleavable.
The method of anyone of the preceding claims wherein the PAMAM-coumarin conjugates are PAMAM-coumarin-NEt2.
The method of anyone of the preceding claims wherein the PAMAM-coumarin-active agent nanocomplex has more than 60 folds active agent delivery efficiency compared to a free active agent.
A self-assembly system for drug delivery comprising a modified PAMAM conjugated to one or more photocleavable compound, wherein the photocleavable compound is BODIPY.
The system of anyone of the preceding claims, wherein the BODIPY can be selected from formula (VII), formula (VIII), formula (IX), formula (X), formula (XI), or formula (XII):
A system for drug delivery comprising a BODIPY-modified PAMAM compound (“BMP”) comprising a photocleavable compound BODIPY bound to one or more active agents to form a BODIPY-modified PAMAM active agent nanocomplex.
The system of anyone of the preceding claims wherein the BMP comprises 2, 14, 26, 50 or 60 BODIPY conjugates forming BMP2, BMP14, BMP26, BMP50 or BMP60, respectively.
The system of anyone of the preceding claims wherein the BODIPY-modified PAMAM is BODIPY-Me2-modified PAMAM (BMMP), BODIPY-F2-modified PAMAM (BFMP), BODIPY-Et2-modified-PAMAM (BEMP), BODIPY-Pr2-modified-PAMAM (BPMP) or a combination thereof.
The system of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex is coated with hyaluronic acid (HA) and human serum albumin (HSA).
The system of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex is HHcB60 rHSA.
The system of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex has a diameter of 110-150 nm and a polydispersity index (PDI) of 0.090-0.115.
The system of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex has a diameter of 122.2 nm and a polydispersity index (PDI) of 0.109.
The system of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex has high stability against high ionic strength and binding competition of serum active agents.
The system of anyone of the preceding claims wherein the BMP comprises 14 BODIPY or 60 BODIPY.
The system of anyone of the preceding claims wherein the BMP is BMP14 or BMP60.
A method of delivering a drug to a subject at a target site comprising:
- (i) providing a BODIPY-modified PAMAM compound (BMP) that is bound to one or more active agents to form a BODIPY modified PAMAM active agent nanocomplex;
- (ii) administering the nanocomplex to the subject;
- and (iii) irradiating the nanocomplex at the target site with a light source to release the one or more active agents.
The method of anyone of the preceding claims wherein the BMP comprises 2, 14, 26, 50 or 60 BODIPY conjugates forming BMP2, BMP14, BMP26, BMP50 or BMP60 respectively.
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM is BODIPY-Me2-modified PAMAM (BMMP), BODIPY-F2-modified PAMAM (BFMP), BODIPY-Et2-modified-PAMAM (BEMP), BODIPY-Pr2-modified-PAMAM (BPMP) or a combination thereof.
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex is coated with hyaluronic acid (HA) and human serum albumin (HSA).
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex is HHcB60 rHSA.
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex has a diameter of 110-150 nm and a polydispersity index (PDI) of 0.090-0.115.
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex has a diameter of 122.2 nm and a polydispersity index (PDI) of 0.109.
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex has high stability against high ionic strength and binding competition of serum active agents.
The method of anyone of the preceding claims wherein the BMP comprises 14 BODIPY or 60 BODIPY.
The method of anyone of the preceding claims wherein the BMP is BMP14 or BMP60.
The method of anyone of the preceding claims wherein the light source has a wavelength of 520 nm.
The method of anyone of the preceding claims wherein the light source has a wavelength of 495-750 nm.
The method of anyone of the preceding claims wherein the light source has a wavelength of 620-750 nm.
The method of anyone of the preceding claims wherein the nanocomplex releases one or more active agents within 2 minutes of light irradiation at 50 mW/cm2 or other time periods and irradiances.
The method of anyone of the preceding claims wherein the target site is intracellular.
The method of anyone of the preceding claims wherein the target site is the eye or skin.
A method of treating cancer in a subject in need thereof comprising:
- (i) administering a BODIPY-modified PAMAM compound that is bound to an active agent to form a BODIPY-modified PAMAM active agent nanocomplex;
- and (ii) irradiating the nanocomplex at the target site with a light source to release the active agent.
The method of anyone of the preceding claims wherein the BMP comprises 2, 14, 26, 50 or 60 BODIPY conjugates forming BMP2, BMP14, BMP26, BMP50 or BMP60, respectively.
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM is BODIPY-Me2-modified PAMAM (BMMP), BODIPY-F2-modified PAMAM (BFMP), BODIPY-Et2-modified-PAMAM (BEMP), BODIPY-Pr2-modified-PAMAM (BPMP), or a combination thereof.
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex is coated with hyaluronic acid (HA) and human serum albumin (HSA).
The method of anyone of the preceding claims wherein the active agent is glucose oxidase, caspase-3, horseradish peroxidase, RNase A, or chymotrypsin.
The method of anyone of the preceding claims wherein the active agent retains its activity.
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex is HHcB60 rHSA.
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex has a diameter of 110-150 nm and a polydispersity index (PDI) of 0.090-0.115.
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex has a diameter of 122.2 nm and a polydispersity index (PDI) of 0.109.
The method of anyone of the preceding claims wherein the BODIPY-modified PAMAM active agent nanocomplex has high stability against high ionic strength and binding competition of serum active agents.
The method of anyone of the preceding claims wherein the BMP comprises 14 BODIPY or 60 BODIPY.
The method of anyone of the preceding claims wherein the BMP is BMP14 or BMP60.
The method of anyone of the preceding claims wherein the light source has a wavelength of 520 nm.
The method of anyone of the preceding claims wherein the light source has a wavelength of 495-550 nm.
The method of anyone of the preceding claims wherein the light source has a wavelength of 620-750 nm.
The method of anyone of the preceding claims wherein the nanocomplex releases one or more active agents within 2 minutes of light irradiation at 50 mW/cm2 or other time periods and irradiances.
The method of anyone of the preceding claims wherein the target site is intracellular.
The method of anyone of the preceding claims wherein the target site is the eye or skin.
The method of anyone of the preceding claims wherein the target site is a tumor.
The method of anyone of the preceding claims wherein the target site is an antigen-presenting cell.
The method of anyone of the preceding claims wherein the antigen-presenting cell is a macrophage.
The method of anyone of the preceding claims wherein the active agent is OVA257-264 peptide (SIINFEKL).
Dependencies are inferred from the claim text.