Retention of peptide-based vesicles in murine knee joints after intra-articular injection

Dunshee, Lucas C.; McDonough, Ryan C.; Price, Christopher; Kiick, Kristi L.

doi:10.1016/j.jddst.2022.103532

Cited by 3 publications

(9 citation statements)

References 93 publications

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“…54−56 Therefore, peptide-based nanocarriers based on ECnVs that improve bioavailability and limit off-target effects could have value in the delivery of these cargoes, through demonstrated improved retention via extracellular targeting, electrostatic interactions, and/or tissue affinity to extracellular matrix (ECM). 50 Previous studies have been conducted on Dex incorporated in PLGA microsphere/PLGA microsphere-containing hydrogels, 57,58 with delivery sustained from the microspheres. Hwang et al 49 have also compared the release of vancomycin (Van) from Van-loaded ECnVs incorporated into hydrogels with Vanloaded liposomes (DSPE-PEG)-incorporated into hydrogels.…”

Section: ■ Introductionmentioning

confidence: 99%

“…ECnVs remain intact for at least 7 days of dialysis at low ECnV concentration and retain their vesicular structure after centrifugation and resuspension and even after one year of ambient storage in aqueous solution (data not shown). Furthermore, fluorophore-labeled ECnVs are able to survive several steps of dehydration through graded ethanol, as well as the xylene clearing and molten paraffin infiltration necessary for histological processing …”

Section: Introductionmentioning

confidence: 99%

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Controlled Release of Drugs from Extracellular Matrix-Derived Peptide-Based Nanovesicles through Tailored Noncovalent Interactions

Huang,

Hwang,

Anilkumar

et al. 2024

Biomacromolecules

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Elastin−collagen nanovesicles (ECnV) have emerged as a promising platform for drug delivery due to their tunable physicochemical properties and biocompatibility. The potential of nine distinct ECnVs to serve as drug-delivery vehicles was investigated in this study, and it was demonstrated that various small-molecule cargo (e.g., dexamethasone, methotrexate, doxorubicin) can be encapsulated in and released from a set of ECnVs, with extents of loading and rates of release dictated by the composition of the elastin domain of the ECnV and the type of cargo. Elastinlike peptides (ELPs) and collagen-like peptides (CLPs) of various compositions were produced; the secondary structure of the corresponding peptides was determined using CD, and the morphology and average hydrodynamic diameter (∼100 nm) of the ECnVs were determined using TEM and DLS. It was observed that hydrophobic drugs exhibited slower release kinetics than hydrophilic drugs, but higher drug loading was achieved for the more hydrophilic Dox. The collagen-binding ability of the ECnVs was demonstrated through a 2D collagen-binding assay, suggesting the potential for longer retention times in collagen-enriched tissues or matrices. Sustained release of drugs for up to 7 days was observed and, taken together with the collagen-binding data, demonstrates the potential of this set of ECnVs as a versatile drug delivery vehicle for longer-term drug release of a variety of cargo. This study provides important insights into the drug delivery potential of ECnVs and offers useful information for future development of ECnV-based drug delivery systems for the treatment of various diseases.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Controlled Release of Drugs from Extracellular Matrix-Derived Peptide-Based Nanovesicles through Tailored Noncovalent Interactions

Huang,

Hwang,

Anilkumar

et al. 2024

Biomacromolecules

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“…They demonstrated more than 7‐day retainment of the IA injected nanoparticles in the healthy mouse knee joint. However, due to the lack of a control experiment, it is unclear if this retention was a direct result of the peptide's affinity to collagen 27 …”

Section: Introductionmentioning

confidence: 99%

“…However, due to the lack of a control experiment, it is unclear if this retention was a direct result of the peptide's affinity to collagen. 27 In this research, we investigated whether CHPs could improve the retention time of small molecules in the joint space after IA injection. We examined if CHP conjugation could extend the retention time of near-infrared fluorophores (NIRF) markers in vivo after IA injection in healthy and osteoarthritic rat knee joints.…”

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confidence: 99%

Targeting damaged collagen for intra‐articular delivery of therapeutics using collagen hybridizing peptides

Luke

Bhuket

et al. 2023

Journal Orthopaedic Research

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The objective of this study was to investigate the potential of collagen hybridizing peptides (CHPs), which bind to denatured collagen, to extend the retention time of near‐infrared fluorophores (NIRF) following intra‐articular (IA) injection in rat knee joints. CHPs were synthesized with a NIRF conjugated to the N‐terminus. Male Sprague−Dawley rats were assigned to one of four experimental groups: healthy, CHP; osteoarthritis (OA), CHP; healthy, scrambled‐sequence CHP (sCHP), which has no collagen binding affinity; or OA, sCHP. Animals in the OA groups received an IA injection of monosodium iodoacetate to induce OA. All animals then received the corresponding CHP injection. Animals were imaged repeatedly over 2 weeks using an in vivo fluorescence imaging system. Joint components were isolated and imaged to determine CHP binding distribution. Safranin‐O and Fast Green histological staining was performed to confirm the development of OA. CHPs were found to be retained within the joint following IA injection in both healthy and OA animals for the full study period. In contrast, sCHP signal was negligible by 24−48 h. CHP signal was significantly greater (p < 0.05) in OA joints when compared to healthy joints. At the 2‐week end point, multiple joint components retained CHPs, including cartilage, meniscus, and synovium. CHPs dramatically extended the retention time of NIRFs following IA injection in healthy and OA knee joints by binding to multiple collagenous tissues in the joint. These results support the pursuit of further research to develop CHP based therapeutics for IA treatment of OA.

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“…They demonstrated more than 7-day retainment of the IA injected nanoparticles in the healthy mouse knee joint. However, due to the lack of a control experiment, it is unclear if this retention was a direct result of the peptide's affinity to collagen [23] .…”

Section: Introductionmentioning

confidence: 99%

Targeting Damaged Collagen for Intra-Articular Delivery of Therapeutics using Collagen Hybridizing Peptides

Luke

Bhuket

et al. 2022

Preprint

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The objective of this study was to investigate the potential of collagen hybridizing peptides (CHPs), which bind to denatured collagen, to extend the retention time of near-infrared fluorophores (NIRF) following intra-articular (IA) injection in rat knee joints. CHPs were synthesized with a NIRF conjugated to N-terminus. Male Sprague-Dawley rats were assigned to one of four experimental groups: healthy, CHP; osteoarthritis (OA), CHP; healthy, scrambled-sequence CHP (sCHP), which has no collagen binding affinity; or OA, sCHP. Animals in the OA groups received an IA injection of monosodium iodoacetate to induce OA. All animals then received the corresponding CHP injection. Animals were imaged repeatedly over two weeks using an in vivo fluorescence imaging system. Joint components were isolated and imaged to determine CHP binding distribution. Safranin-O and Fast Green histological staining was performed to confirm the development of OA. CHPs were found to be retained within the joint following IA injection in both healthy and OA animals for the full study period. In contrast, sCHPs were cleared within 24-48 hours. CHP signal was significantly greater (p<0.05) in OA joints when compared to healthy joints. At the two-week end point, multiple joint components retained CHPs, including cartilage, meniscus, and synovium. CHPs extended the retention time of NIRFs following IA injection in healthy and OA knee joints by binding to multiple collagenous tissues in the joint. These results support the pursuit of further research on CHP based therapeutics for IA treatment of OA.

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Retention of peptide-based vesicles in murine knee joints after intra-articular injection

Cited by 3 publications

References 93 publications

Controlled Release of Drugs from Extracellular Matrix-Derived Peptide-Based Nanovesicles through Tailored Noncovalent Interactions

Controlled Release of Drugs from Extracellular Matrix-Derived Peptide-Based Nanovesicles through Tailored Noncovalent Interactions

Targeting damaged collagen for intra‐articular delivery of therapeutics using collagen hybridizing peptides

Targeting Damaged Collagen for Intra-Articular Delivery of Therapeutics using Collagen Hybridizing Peptides

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