PMID- 26896317 OWN - NLM STAT- MEDLINE DCOM- 20170117 LR - 20170123 IS - 1530-9932 (Electronic) IS - 1530-9932 (Linking) VI - 18 IP - 1 DP - 2017 Jan 1 TI - Preparation, Characterization, and Optimization of Folic Acid-Chitosan-Methotrexate Core-Shell Nanoparticles by Box-Behnken Design for Tumor-Targeted Drug Delivery. PG - 115-129 LID - 10.1208/s12249-015-0445-3 [doi] AB - The objective of this study was to investigate the combined influence of independent variables in the preparation of folic acid-chitosan-methotrexate nanoparticles (FA-Chi-MTX NPs). These NPs were designed and prepared for targeted drug delivery in tumor. The NPs of each batch were prepared by coaxial electrospray atomization method and evaluated for particle size (PS) and particle size distribution (PSD). The independent variables were selected to be concentration of FA-chitosan, ratio of shell solution flow rate to core solution flow rate, and applied voltage. The process design of experiments (DOE) was obtained with three factors in three levels by Design expert software. Box-Behnken design was used to select 15 batches of experiments randomly. The chemical structure of FA-chitosan was examined by FTIR. The NPs of each batch were collected separately, and morphologies of NPs were investigated by field emission scanning electron microscope (FE-SEM). The captured pictures of all batches were analyzed by ImageJ software. Mean PS and PSD were calculated for each batch. Polynomial equation was produced for each response. The FE-SEM results showed the mean diameter of the core-shell NPs was around 304 nm, and nearly 30% of the produced NPs are in the desirable range. Optimum formulations were selected. The validation of DOE optimization results showed errors around 2.5 and 2.3% for PS and PSD, respectively. Moreover, the feasibility of using prepared NPs to target tumor extracellular pH was shown, as drug release was greater in the pH of endosome (acidic medium). Finally, our results proved that FA-Chi-MTX NPs were active against the human epithelial cervical cancer (HeLa) cells. FAU - Naghibi Beidokhti, Hamid Reza AU - Naghibi Beidokhti HR AD - Department of Pharmaceutical Engineering, Faculty of Engineering, University of Tehran, Tehran, Iran. FAU - Ghaffarzadegan, Reza AU - Ghaffarzadegan R AD - Medical Plants Research Center, Institute of Medical Plants, ACECR, Karaj, Iran. FAU - Mirzakhanlouei, Sasan AU - Mirzakhanlouei S AD - Medical Plants Research Center, Institute of Medical Plants, ACECR, Karaj, Iran. FAU - Ghazizadeh, Leila AU - Ghazizadeh L AD - Pasteur Institute of Iran, National Cell Bank of Iran, Tehran, Iran. FAU - Dorkoosh, Farid Abedin AU - Dorkoosh FA AD - Medical Biomaterial Research Center, Tehran University of Medical Sciences, Tehran, Iran. Drorkoosh@tums.ut.ac.ir. AD - Department of Pharmaceutics, Tehran University of Medical Sciences, Tehran, Iran. Drorkoosh@tums.ut.ac.ir. LA - eng PT - Journal Article DEP - 20160219 PL - United States TA - AAPS PharmSciTech JT - AAPS PharmSciTech JID - 100960111 RN - 0 (Drug Carriers) RN - 9012-76-4 (Chitosan) RN - 935E97BOY8 (Folic Acid) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Cell Line MH - Cell Line, Tumor MH - Chemistry, Pharmaceutical/methods MH - Chitosan/administration & dosage/*chemistry MH - Drug Carriers/chemistry MH - Drug Delivery Systems/methods MH - Folic Acid/administration & dosage/*chemistry MH - HeLa Cells MH - Humans MH - Methotrexate/administration & dosage/*chemistry MH - Nanoparticles/administration & dosage/*chemistry MH - Particle Size OTO - NOTNLM OT - box-Behnken design OT - coaxial electrospray OT - folic acid-chitosan nanoparticles OT - methotrexate OT - optimization EDAT- 2016/02/21 06:00 MHDA- 2017/01/18 06:00 CRDT- 2016/02/21 06:00 PHST- 2015/07/06 00:00 [received] PHST- 2015/10/19 00:00 [accepted] PHST- 2016/02/21 06:00 [pubmed] PHST- 2017/01/18 06:00 [medline] PHST- 2016/02/21 06:00 [entrez] AID - 10.1208/s12249-015-0445-3 [pii] AID - 10.1208/s12249-015-0445-3 [doi] PST - ppublish SO - AAPS PharmSciTech. 2017 Jan 1;18(1):115-129. doi: 10.1208/s12249-015-0445-3. Epub 2016 Feb 19.