Composite Microgels Loaded with Doxorubicin-Conjugated Amine-Functionalized Zinc Ferrite Nanoparticles for Stimuli-Responsive Sustained Drug Release

Shirisha Bellala,1,* Karthika Viswanathan,2,* Ujwala Guntakanti,3 Anitha Kowthalam,1 Sung Soo Han,4 Madhusudana Rao Kummara,4 Sreekanth Reddy Obireddy,1,5 Wing-Fu Lai5– 7 1Department of Chemistry, Sri Krishnadevaraya University, Anantapur, Andhra Pradesh, 515003, India; 2Department of Nanoscience and Technology, Alagappa University, Karaikudi, Tamil Nadu, 630 003, India; 3Department of Chemistry, G. Pulla Reddy Engineering College, Kurnool, Andhra Pradesh, 518 007, India; 4School of Chemical Engineering, Yeungnam University, Gyeongsan, 38541, Republic of Korea; 5Department of Urology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Zhejiang, 310014, China; 6School of Food Science and Nutrition, University of Leeds, Leeds, LS2 9JT, UK; 7Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong Special Administrative Region, China*These authors contributed equally to this workCorrespondence: Wing-Fu Lai, Email rori0610@graduate.hku.hk; Sreekanth Reddy Obireddy, Email sreekanthchem7@gmail.comPurpose: The purpose of this study is to address the need for efficient drug delivery with high drug encapsulation efficiency and sustained drug release. We aim to create nanoparticle-loaded microgels for potential applications in treatment development.Methods: We adopted the process of ionic gelation to generate microgels from sodium alginate and carboxymethyl cellulose. These microgels were loaded with doxorubicin-conjugated amine-functionalized zinc ferrite nanoparticles (AZnFe-NPs). The systems were characterized using various techniques. Toxicity was evaluated in MCF-7 cells. In vitro release studies were conducted at different pH levels at 37 oC, with the drug release kinetics being analyzed using various models.Results: The drug encapsulation efficiency of the created carriers was as high as 70%. The nanoparticle-loaded microgels exhibited pH-responsive behavior and sustained drug release. Drug release from them was mediated via a non-Fickian type of diffusion.Conclusion: Given their high drug encapsulation efficiency, sustained drug release and pH-responsiveness, our nanoparticle-loaded microgels show promise as smart carriers for future treatment applications. Further development and research can significantly benefit the field of drug delivery and treatment development.Keywords: sodium alginate, carboxymethyl cellulose, doxorubicin, zinc ferrite nanoparticles, microgels