Nanoparticles in thermosensitive gel based composite nanosystem for ocular diseases

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Ophthalmology

Background:

• Developing effective long-term ocular drug delivery systems for macromolecules is challenging.
• Pentablock (PB) copolymers offer a promising platform for advanced nanoformulations.

Purpose of the Study:

• To design and characterize pentablock copolymer-based composite nanosystems for sustained delivery of macromolecules to the back of the eye.
• To evaluate the influence of copolymer molecular weight and macromolecule size on drug release kinetics.
• To assess the in vitro biocompatibility of the developed nanosystems.

Main Methods:

• Synthesis of pentablock copolymers (PB-A, PB-B) and thermosensitive gel (PB-C) via ring-opening polymerization.
• Characterization of copolymers using 1H-NMR spectroscopy and PXRD.
• Encapsulation of model macromolecules (lysozyme, IgG-Fab, IgG) into nanoparticles (NPs) using double emulsion solvent evaporation.
• In vitro release studies of NPs alone and within the thermosensitive gel.
• In vitro biocompatibility assessment by measuring cytokine release (IL-1, IL-6, TNF-α).

Main Results:

• PB-B copolymers exhibited higher entrapment efficiency and drug loading compared to PB-A due to increased molecular weight and hydrophobicity.
• Nanoparticles (NPs) ranged from 200-270 nm in size.
• Composite nanosystems demonstrated minimal burst release and sustained drug release over an extended period.
• In vitro studies showed negligible release of inflammatory cytokines, confirming the safety of the PB copolymers.

Conclusions:

• Pentablock copolymer-based composite nanosystems are effective for the long-term ocular delivery of macromolecules.
• The study highlights the importance of copolymer properties and macromolecule characteristics in optimizing drug release profiles.
• These nanosystems represent a promising strategy for treating posterior eye diseases requiring sustained therapeutic levels.