pH-targeted and time-released microparticles of quercetin and lycopene for ulcerative colitis treatment: DoE-based formulation development, pharmacokinetics, and in-vivo proof of concept studies

Abstract

Lycopene (LYC) and quercetin (QRN) exhibit synergistic effects on ulcerative colitis (UC) treatment due to their anti-inflammatory and antioxidant properties. This study aimed to develop a microparticle formulation utilizing pH-sensitive and time-release-based polymers, namely Eudragit L and Eudragit RS, respectively, to achieve colon-targeted and controlled-release delivery.

Subsequently, pharmacokinetics and UC therapy proof-of-concept studies were conducted. The box-Behnken design was employed to develop and optimize the LYC-QRN microparticles, characterized by particle size and distribution, entrapment efficiency (EE), and drug loading, followed by morphology, molecular, thermal and crystallinity evaluations. The polymers primarily contributed to LYC-QRN encapsulation and loading, while the drug concentration influenced particle size behavior. The optimized formulation was achieved using 4.10% Eudragit RS, 0.76% Eudragit L, and a drug concentration of 7.82%, resulting in an EE of >50%. QRN and LYC loading were approximately 50 and 25 mg/g, respectively, and the particle size was nearly 1 µm, exhibiting minimal variation.

Characterization demonstrated that the drug in the microparticle dispersed molecularly as an amorphous system, devoid of any chemical interactions. The drug was released at a specific pH-triggering system, enhancing its bioavailability by 3.5-fold. In-vivo evaluation demonstrated that LYC-QRN microparticles effectively cured chronic colon inflammation and protected the gastric mucus layers.