Poly(malic acid)-budesonide nanoconjugates embedded in microparticles for lung administration.

Area of Science:

• * Pharmaceutical Nanotechnology
• * Pulmonary Drug Delivery
• * Polymer Chemistry

Background:

• * Inhaled glucocorticoids are crucial for treating pulmonary inflammation but face challenges with side effects and efficacy.
• * Nanoparticles offer enhanced cellular uptake and targeted delivery, while microparticles improve alveolar deposition.
• * Combining nanoparticle and microparticle advantages can optimize inhaled drug formulations.

Purpose of the Study:

• * To design and synthesize polymer-drug conjugates for nanoparticle formation.
• * To encapsulate these nanoconjugates within microparticles for enhanced pulmonary delivery.
• * To evaluate the in vitro and in vivo performance of the nano-embedded microparticles (NEMs).

Main Methods:

• * Synthesis of poly(malic acid)-budesonide (PMAB) polymer-drug conjugates.
• * Self-assembly of PMAB into nanoconjugates and subsequent encapsulation into microparticles via spray-drying with L-leucine.
• * In vitro release studies and anti-inflammatory assays using RAW 264.7 macrophages.
• * In vivo pharmacokinetic studies in rats to assess lung distribution.

Main Results:

• * PMAB conjugates self-assembled into 80-100 nm nanoconjugates with high drug loading (up to 73 wt%).
• * Nanoconjugates demonstrated sustained budesonide release and preserved anti-inflammatory activity in vitro.
• * NEMs exhibited optimal aerodynamic properties for alveolar deposition and sustained budesonide release in rat lungs for 48 hours.

Conclusions:

• * Nano-embedded microparticles (NEMs) provide a promising platform for efficient inhaled budesonide delivery.
• * The formulation allows for sustained drug release and distribution within lung tissues.
• * This approach holds potential for improved treatment of pulmonary inflammatory diseases with reduced systemic exposure.