HA particles as resourceful cancer, steroidal and antibiotic drug delivery device with sustainable and multiple drug release capability

Abstract

Hyaluronic acid (HA) particles with divinyl sulfone (DVS) crosslinking at 10% mole ratio (HA macromolecule repeating units) were prepared and demonstrated as versatile drug carriers with sustainable and long-term release capabilities for cancer drugs, corticosteroid, and antibiotics. Two different methods were chosen in drug loading process; encapsulation for cancer drugs, 5-fluorouracil (5FU), mitomycin C (MMC), and doxorubicin (Dox), and dual drug conjugation for anti-inflammatory glucocorticoid dexamethasone (Dex) and antibiotic ciprofloxacin (Cipro) drugs, respectively. It was demonstrated that HA particles prepared during drug encapsulation were attained smaller sizes with 833 ± 46, 867 ± 50, 728 ± 41 nm for 5FU, MMC, and Dox, respectively. Bare and drug loaded HA particles were shown to be blood compatible with the highest hemolytic ratio of 3.1 ± 0.12% for HA-Dex-Cipro conjugates and fairly good blood clotting index with minimum 71.7 ± 6.0% for MMC encapsulated HA particles. Drug release studies from HA particles indicated that depending on the types of cancer drugs, it is possible to gradually release the drug in long-term up to 300 h in linear fashions with the highest release of 9.34 ± 2.25 mg/g for 5FU. Similarly, drug conjugated HA-Dex-Cipro particles were also showed linear dual drug release up to 100 h at physiological conditions, pH 7.4 and 37.5 °C.

GRAPHICAL ABSTRACT

Keywords:

• Hyaluronic acid macromolecules
• multiple drug release
• cancer drug
• biological macromolecule derived micro/nano particles
• controlled release