Multi-functional chitosan copolymer modified nanocrystals as oral andrographolide delivery systems for enhanced...

Modifying nanocrystals with functional materials have been common strategy to enlarge the enhancing ability on oral absorption via nanocrystals; however, whether the functional materials have played their full enhancing ability in oral absorption is still unknown. In this study, we synthetized a novel chitosan-based copolymer (the copolymer of sodium dodecyl sulfate (SDS), chitosan (CS) and D-α-Tocopherol polyethylene glycol 1000 succinate, SDS-CS-TPGS), and modified nanocrystals with this copolymer, aiming to enhance the oral absorption of polymer andrographolide (ADR). In real-time distribution study, we found the distribution of ADR, SDS, CS and TPGS varies in gastrointestinal tract, while the distribution of ADR and SDS-CS-TPGS was similar, revealing the SDS-CS-TPGS could able to participate in the absorption process of andrographolide timely. To explore the oral absorption enhancing ability of SDS-CS-TPGS, we prepared a series of nanocrystals modified with different materials and explored their pharmacokinetic performances on SD rats. The results showed the nanocrystals modified with SDS-CS-TPGS (S-C-TANs) exhibited the highest bioavailability, which could enhance the AUC_0-∞ of ADR from 1.291 mg/L*h to 5.275 mg/L*h (enhanced for about 4.09-folds). The enhanced anti- inflammatory efficacy was also found on ICR mice by employing ear swelling rate, TNF-α, IL-1β and IL-6 and pharmacodynamic index. These results indicated that modified with synthesized copolymer containing different functional stabilizers is an efficient strategy to enlarge the enhancing ability on oral absorption of nanocrystals.