Redox responsive poly(allylamine)/eudragit S-100 nanoparticles for dual drug delivery in colorectal cancer

Herein, we report redox responsive, colon cancer targeting poly(allylamine) (PA)/eudragit S-100 (EU) nanoparticles (PAEU NPs) (≈59 nm). These disulfide crosslinked PAEU NPs are developed via air oxidation of thiolated PA and thiolated EU, eliminating the need of any external crosslinking agent for dual drug delivery. PAEU NPs can effectively encapsulate both hydrophilic doxorubicin (DOX) and hydrophobic curcumin (Cur) drug with ≈85 % and ≈97 % encapsulation efficiency respectively. Here, the combination of drugs having different anticancer mechanism offers the possibility of developing nanosystem with enhanced anticancer efficacy.

Highlights

• Redox responsive poly(allylamine)/eudragit S-100 nanoparticles were fabricated.

• Both hydrophilic doxorubicin and hydrophobic curcumin drugs were loaded in PAEU NPs.

• Redox responsive drug release behaviour in the presence of GSH enzyme

• Dual drug loaded PAEU NPs exhibited higher cytotoxicity than free drugs.

• In vivo biodistribution studies show the retention of PAEU NPs in the colon region up to 24 h.

The developed PAEU NPs show good colloidal stability and low drug release under physiological conditions, while high DOX (≈98 %) and Cur (≈93 %) release is observed in reducing environment (10 mM GSH). Further, DOX and Cur loaded PAEU NPs exhibit higher cancer cell killing efficiency as compared to individual free drugs. In vivo biodistribution studies with Balb/C mice display the retention of PAEU NPs in the colon region up to 24 h presenting the developed approach as an efficient way for colorectal cancer therapy.

Read more

Aastha Gupta, Ankur Sood, Ankita Dhiman, Nishith Shrimali, Ritu Singhmar, Prasenjit Guchhait, Garima Agrawal, Redox responsive poly(allylamine)/eudragit S-100 nanoparticles for dual drug delivery in colorectal cancer, Biomaterials Advances, Volume 143, 2022, 213184, ISSN 2772-9508, https://doi.org/10.1016/j.bioadv.2022.213184.