Multifunctional polymeric nanocapsules with enhanced cartilage penetration and retention for osteoarthritis treatment

J Control Release. 2024 Oct:374:466-477. doi: 10.1016/j.jconrel.2024.08.031. Epub 2024 Aug 27.

Abstract

Osteoarthritis (OA) is a prevalent joint disease characterized by cartilage degeneration and subchondral bone homeostasis imbalance. Effective topical OA therapy is challenging, as therapeutic drugs often suffer from insufficient penetration and rapid clearance. We develop miniature polydopamine (PDA) nanocapsules (sub-60 nm), which are conjugated with collagen-binding polypeptide (CBP) and loaded with an anabolic drug (i.e., parathyroid hormone 1-34, PTH 1-34) for efficient OA treatment. Such multifunctional polymeric nanocapsules, denoted as PDA@CBP-PTH, possess deformability when interacting with the dense collagen fiber networks, enabling the efficient penetration into 1 mm cartilage in 4 h and prolonged retention within the joints up to 28 days. Moreover, PDA@CBP-PTH nanocapsules exhibit excellent reactive oxygen species scavenging property in chondrocytes and enhance the anabolism in subchondral bone. The nanosystem, as dual-mode treatment for OA, demonstrates rapid penetration, long-lasting effects, and combinational therapeutic impact, paving the way for reversing the progression of OA for joint health care.

Keywords: Antioxidation; Osteoarthritis; Osteogenesis; Polydopamine; Polymeric Nanocapsule.

MeSH terms

  • Animals
  • Cartilage / drug effects
  • Cartilage / metabolism
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Humans
  • Indoles* / administration & dosage
  • Indoles* / pharmacokinetics
  • Male
  • Nanocapsules* / chemistry
  • Osteoarthritis* / drug therapy
  • Parathyroid Hormone / administration & dosage
  • Parathyroid Hormone / pharmacokinetics
  • Parathyroid Hormone / therapeutic use
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacokinetics
  • Peptides / administration & dosage
  • Peptides / chemistry
  • Peptides / pharmacokinetics
  • Polymers* / chemistry
  • Reactive Oxygen Species / metabolism

Substances

  • Nanocapsules
  • Polymers
  • polydopamine
  • Indoles
  • Parathyroid Hormone
  • Peptides
  • Reactive Oxygen Species
  • Peptide Fragments