National Science & Technology Development Agency - Thailand; National Nanotechnology Center (NANOTEC); University of Victoria; Mahidol University; Mahidol University
Primary central nervous system lymphoma (PCNSL) is a form of extranodal non-Hodgkin's B-cell lymphoma limited to the CNS. The treatment of PCNSL is ineffective partly due to the blood-brain barrier (BBB) restriction of delivery of many drugs including anti-CD20 (Rituximab; RTX) which is a standard treatment for systemic B cell lymphomas. In this study, liposome with tween-80 surface modification was fabricated and conjugated with RTX for enhancing BBB penetration to target lymphoma cells in the CNS. Physicochemical characterizations of Lip/RTX were performed and spherical shape liposomes with narrow size distribution were demonstrated by TEM. An average diameter of Lip/RTX was 168.57 +/- 1.57 nm with the percentage of RTX conjugation at 90.94. Cell internalization monitored by flow cytometry confirmed that conjugation of RTX promoted liposome entry into Raji cells expressing CD20. Antitumor activity of Lip/RTX was comparable to free RTX indicating that RTX moieties on liposome remained their therapeutic function. In addition, Lip/RTX inhibited tumor aggressiveness by limiting cell migration and invasion. Systemic administration of Lip/RTX significantly prolonged survival of mice harboring intracranial lymphoma xenografts. Taken together, Lip/RTX presents a new potential treatment for patients with PCNSL.
National Science and Technology Development Agency (NPT-RNN) [P1851732]; National Research Council of Thailand (NRCT) [N41A640102]; Research Network NANOTEC (RNN) program of the National Nanotechnology Center (NANOTEC); Ministry of Higher Education, Science, Research and Innovation (MHESI) , Thailand and Siriraj Research Fund; Faculty of Medicine Siriraj Hospital, Mahidol University [R016141027]; NSTDA
