IP Library › Granted Patent US 12,564,639
Granted Patent B2
US 12,564,639 · App. 18/310,234 · Granted Mar 3, 2026

Cationic nanostructures for intra-cartilage delivery of contrast agents and diagnostic uses thereof

Inventors: Ambika Bajpayee (Cambridge, MA); Chenzhen Zhang (Boston, MA); Armin Vedadghavami (Boston, MA); Tengfei He (Malden, MA)
Assignee: Northeastern University
A61K47/60A61K9/0019A61K31/573A61K38/18A61K47/22A61K47/645A61K49/0438B82Y5/00
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Quick Facts
Patent No.
US 12,564,639
App. No.
18/310,234
Granted
Mar 3, 2026
Kind
B2
Abstract

The present invention provides a platform for the delivery of small molecule drugs or contrast agents to joints and other soft tissues. The platform enables penetration of the drug through the full thickness of cartilage and long intra-cartilage residence time by leveraging electrostatic interactions between the cationic platform and the anionic cartilage matrix. Described herein are compounds and complexes that fit this platform. Also provided are methods of treating a joint disease with the compounds and complexes of the invention, and methods of imaging joints and other soft tissue.

Claims (34)

1 . A complex, comprising:

a residue of a contrast agent and a cationic peptide;

wherein the net charge of the cationic peptide is +7 to +20 inclusive;

the residue of the contrast agent is covalently bonded to the cationic peptide;

the contrast agent is selected from the group consisting of diatrizoate, metrizoate, iothalamate, and ioxaglate; and

the cationic peptide is selected from the group consisting of: RRAAAARRAAAARRAAAARR (SEQ ID NO: 1);

RRRRAARRRAARRRAARRRR (SEQ ID NO: 2);

(ARRRAARA) 4 (SEQ ID NO: 3); and

RRRRRRRRRRRRRRRRRRRR (SEQ ID NO: 4).

2 . The complex of claim 1 , wherein the cationic peptide is

(SEQ ID NO: 1)

RRAAAARRAAAARRAAAARR.

3 . The complex of claim 1 , wherein the contrast agent is ioxaglate.

4 . The complex of claim 1 , wherein the cationic peptide is

(SEQ ID NO: 2)

RRRRAARRRAARRRAARRRR.

5 . A complex, comprising:

a residue of a contrast agent and a cationic peptide;

wherein the net charge of the cationic peptide is +7 to +20 inclusive;

the residue of the contrast agent is covalently bonded to the cationic peptide; and

the cationic peptide is selected from the group consisting of: RRAAAARRAAAARRAAAARR (SEQ ID NO: 1);

RRRRAARRRAARRRAARRRR (SEQ ID NO: 2);

(ARRRAARA) 4 (SEQ ID NO: 3); and

RRRRRRRRRRRRRRRRRRRR (SEQ ID NO: 4).

6 . The complex of claim 5 , wherein the cationic peptide is RRAAAARRAAAARRAAAARR (SEQ ID NO: 1).

7 . The complex of claim 5 , wherein the cationic peptide is

(SEQ ID NO: 2)

RRRRAARRRAARRRAARRRR.

8 . The complex of claim 3 , wherein the cationic peptide is RRAAAARRAAAARRAAAARR (SEQ ID NO: 1).

9 . The complex of claim 3 , wherein the cationic peptide is RRRRAARRRAARRRAARRRR (SEQ ID NO: 2).

10 . The complex of claim 1 , wherein the cationic peptide is (ARRRAARA) 4 (SEQ ID NO: 3).

11 . The complex of claim 1 , wherein the cationic peptide is RRRRRRRRRRRRRRRRRRRR (SEQ ID NO: 4).

12 . The complex of claim 5 , wherein the cationic peptide is (ARRRAARA) 4 (SEQ ID NO: 3).

13 . The complex of claim 5 , wherein the cationic peptide is RRRRRRRRRRRRRRRRRRRR (SEQ ID NO: 4).

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 7, 2023
From: BAJPAYEE, AMBIKA; ZHANG, CHENZHEN; VEDADGHAVAMI, ARMIN; HE, TENGFEI
To: NORTHEASTERN UNIVERSITY
Reel/Frame 064825/0683 →
Continuity (3)
Division 17093186 · Nov 9, 2020
Provisional Application 62932232 · Nov 7, 2019
Related Publication 20240000953A1 · Jan 4, 2024
References Cited (21)
US 5614214A · Ahl et al. · 1997 [cited by applicant]
US 9289506B2 · Bajpayee et al. · 2016 [cited by applicant]
US 10226427B2 · Bajpayee et al. · 2019 [cited by applicant]
US 20140193508A1 · Bajpayee et al. · 2014 [cited by applicant]
US 20210154307A1 · Bajpayee et al. · 2021 [cited by applicant]
US 20210214217A1 · Lodish et al. · 2021 [cited by applicant]
WO WO2016201323A1 · 2016 [cited by applicant]
WO WO2017173034A1 · 2017 [cited by applicant]
WO WO2018106648A1 · 2018 [cited by applicant]
WO WO2020191361A2 · 2020 [cited by applicant]
WO WO2020191377A1 · 2020 [cited by applicant]
WO WO2024039896A1 · 2024 [cited by applicant]
Vedadghavami, Cartilage penetrating cationic peptide carriers for applications in drug delivery to avascular negatively charged tissues, Acta Biomaterialia 93 (2019) 258-269 (Year: 2019). [cited by examiner]
Pouran, Multi-scale imaging techniques to investigate solute transport across articular cartilage, Journal of Biomechanics vol. 78, Sep. 10, 2018, pp. 10-20 (Year: 218). [cited by examiner]
Jiang, Tumor Imaging by means of proteolytic activation of cell-penetrating pedptgides, PNAS,2004, 101(51), 17867-17892 (Year: 2004). [cited by examiner]
Chang, Pentadecapeptide BPC 157 Enhances the Growth Hormone Receptor Expression in Tendon Fibroblasts, Molecules 2014, 19, 19066-19077, 2014). (Year: 2014). [cited by examiner]
He et al., “Multi-arm Avidin nano-construct for intra-cartilage delivery of small molecule drugs,” J. Control Release, 318: 33 pages (2020). [cited by applicant]
Kumar et al., “Biodegradable block copolymers”, Advanced Drug Delivery Reviews, 53: 23-44 (2001). [cited by applicant]
Vedadghavami et al., “Cartilage penetrating cationic peptide carriers for applications in drug delivery to avascular negatively charged tissues,” Acta Biomaterialia, 93: 258-269 (2019). [cited by applicant]
Warren et al., “Milk exosomes with enhanced mucus penetrability for oral delivery of siRNA”, Biomaterials Science, 9(12): 4217-4512 (2021). [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2023/030686 dated Dec. 12, 2023. [cited by applicant]