INTRODUCTION The administration of cancer medicines through the digestive system is an attractive option. The chemical, physical, and biological barriers in the gastrointestinal tract (GIT) limit the bioavailability of substances. 1 This decreases the likelihood that the medication will be efective in treating a particular disease. Recent nanomedicine and material science developments provided several delivery platforms to overcome multiple hurdles associated with oral administration. These platforms have been generated in recent decades. Because to the existence of active efux from intestinal P-glycoprotein receptors, and doxorubicin hydrochloride (DOX-HCl) have poor oral bioavailability. 2 DOX is a member of the anthracycline glycoside class of drugs. DOX is the anticancer medication of choice for use during the frst phase of treatment for a wide variety of malignancies. Researchers have been motivated to develop novel and cutting-edge strategies for entrapping this medication in various nanocarriers due to the nephrotoxicity and cardiotoxicity associated with doxorubicin. This medication is used to treat a number of diferent cancers. 3 It is possible that oral chemotherapy will allow the cancer cells to be exposed to lower concentrations of anticancer medications. This release over a longer period allows for better efcacy and less adverse efects. In addition, oral chemotherapy can give cancer cells a longer, more continuous exposure to anticancer medicines at a relatively lower concentration and, therefore, safer. Additionally, oral chemotherapy can give the cancer cells a longer period of exposure to a comparatively lower concentration of anticancer drugs, which is a safer concentration due to the longer exposure period. Patients choose oral chemotherapy not only because it has the potential to be more successful and have a lower level of toxicity but also because it is cost-efective, fexible in its dose schedule, and easy. People undergoing cancer treatment may experience an improvement in their “quality of life” due to the development of oral chemotherapy, which has made the possibility of “chemotherapy at home” possible. This might improve the ABSTRACT Doxorubicin hydrochloride (DOX) has low oral bioavailability due to the presence of active efux from intestinal P-glycoprotein receptors. Because of the difculties associated with the oral administration of DOX, there is not yet a commercially available oral formulation of DOX. Nanocarrier system was manufactured utilizing poly (lactic-co-glycolic acid) (PLGA) and treated with chitosan to provide a surface coated. Nanoparticles (NPs) were created using a modifed emulsifcation solvent difusion (nanoprecipitation) method by electrostatic conjugation of chitosan to modify nanoparticle surfaces. The model was built using a Box-Behnken design with three independent components: X1 (PLGA), X2 (poloxamer 188), and X3 (chitosan concentration). The optimized chitosan-PLGA NPs had a mean particle size of 153.6 nm and a positive zeta potential of 21.51 mV. More than 85% DOX permeated through the everted gut by DOX-loaded chitosan-NPs as compared to NPs prepared with PLGA alone. Chitosan nanoparticles caused a 6-fold increase in DOX intestinal permeability. The fndings pointed to the possibility of using chitosan-based nanoparticles of doxorubicin for oral treatment for cancer. Keywords: Chitosan, Design of Experiments, Doxorubicin, Nanoparticles, Oral delivery, PLGA. International Journal of Drug Delivery Technology (2022); DOI: 10.25258/ijddt.12.4.06 How to cite this article: Agrawal SS, Soni G, Pethe A, Yadav KS. Doxorubicin Hydrochloride-loaded Nanoparticles for Oral Delivery: Optimization using Design of Experiments. International Journal of Drug Delivery Technology. 2022;12(4):1521-1526. Source of support: Nil. Confict of interest: None Doxorubicin Hydrochloride-loaded Nanoparticles for Oral Delivery: Optimization using Design of Experiments Surendra S. Agrawal 1 , Govind Soni 2 , Anil Pethe 1 , Khushwant S. Yadav 3* 1 Datta Meghe College of Pharmacy, Datta Meghe Institute of Medical sciences, Deemed University, Wardha, Maharashtra, India 2 Oriental College of Pharmacy and Research, Oriental University, Indore, Madhya Pradesh, India 3 Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s, NMIMS Deemed to be University, Mumbai, Maharashtra, India Received: 16 th October, 2022; Revised: 01 st November, 2022; Accepted: 20 th November, 2022; Available Online: 25 th December, 2022 RESEARCH ARTICLE *Author for Correspondence: khush.yadav@gmail.com