PMID- 33905866 OWN - NLM STAT- MEDLINE DCOM- 20210617 LR - 20210617 IS - 1873-3476 (Electronic) IS - 0378-5173 (Linking) VI - 602 DP - 2021 Jun 1 TI - Development of a high payload, cancer-targeting liposomes of methyl aminolevulinate for intraoperative photodynamic diagnosis/therapy of peritoneal carcinomatosis. PG - 120612 LID - S0378-5173(21)00417-8 [pii] LID - 10.1016/j.ijpharm.2021.120612 [doi] AB - Methyl aminolevulinate (MAL) is a photosensitizer topically used for photodynamic diagnosis (PDD) and photodynamic therapy (PDT) of skin pre-cancers and cancers. In this study, our goal is to expand the application of MAL to dual intraoperative PDD and PDT of peritoneal carcinomatosis. A new liposomal MAL formulation (lipMAL) designed for systemic or intraperitoneal administration was developed. LipMALs prepared by ammonium sulfate gradient technique achieved MAL payload up to 18% (w/w) with drug encapsulation efficiency in the range of 15.1-31.5%. All lipMALs demonstrated controlled MAL release behavior, and achieved strong fluorescence in cancer cells (SKOV3) but minimal fluorescence in non-cancer peritoneal cells (B14FAF28-G3). LipMALs led to significantly higher fluorescence levels than free MAL groups (P < 0.05), up to 6.8-fold of the free MAL fluorescence levels in SKOV3 cells. The PDD performance of lipMALs was also compared with free MAL in SKOV3/ B14FAF28-G3 co-cultures simulating ovarian cancer micrometastases on peritoneal surface. The lipMAL-treated cancer colonies glew more brightly than the free MAL treated colonies and were clearly distinguishable from the dim peritoneum background with unaided eyes. LipMAL also achieved significantly stronger anticancer PDT effects than free MAL both in terms of cell viability and colony-formation (P < 0.05) while demonstrating minimal dark toxicity. To conclude, a new promising aid for the surgeons to achieve more complete resection of tumors and PC micrometastases and clean up any residual cancer cells undetected was developed. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Luan, Shijie AU - Luan S AD - Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA. FAU - Tran, Ngoc T AU - Tran NT AD - Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA. FAU - Xue, Hui-Yi AU - Xue HY AD - Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA. Electronic address: joannex@temple.edu. FAU - Wong, Ho-Lun AU - Wong HL AD - Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA. Electronic address: ho-lun.wong@temple.edu. LA - eng PT - Journal Article DEP - 20210424 PL - Netherlands TA - Int J Pharm JT - International journal of pharmaceutics JID - 7804127 RN - 0 (Liposomes) RN - 0 (Photosensitizing Agents) RN - 88755TAZ87 (Aminolevulinic Acid) SB - IM MH - Aminolevulinic Acid MH - Humans MH - Liposomes MH - *Peritoneal Neoplasms/drug therapy MH - *Photochemotherapy MH - Photosensitizing Agents/therapeutic use MH - *Skin Neoplasms/drug therapy OTO - NOTNLM OT - Liposomes OT - Methyl aminolevulinate OT - Peritonealcarcinomatosis OT - Photodynamic diagnosis OT - Photodynamic therapy EDAT- 2021/04/28 06:00 MHDA- 2021/06/22 06:00 CRDT- 2021/04/27 20:12 PHST- 2020/11/30 00:00 [received] PHST- 2021/03/26 00:00 [revised] PHST- 2021/04/11 00:00 [accepted] PHST- 2021/04/28 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2021/04/27 20:12 [entrez] AID - S0378-5173(21)00417-8 [pii] AID - 10.1016/j.ijpharm.2021.120612 [doi] PST - ppublish SO - Int J Pharm. 2021 Jun 1;602:120612. doi: 10.1016/j.ijpharm.2021.120612. Epub 2021 Apr 24.