Release of doxorubicin from its liposomal coating via high intensity ultrasound

Mikolajczyk,Agata; Khosrawipour,Veria; Kulas,Joanna; Kocielek,Klaudia; Migdal,Pawel; Arafkas,Mohamed; Khosrawipour,Tanja

doi:10.3892/mco.2019.1917

Release of doxorubicin from its liposomal coating via high intensity ultrasound

Authors:
- Agata Mikolajczyk
- Veria Khosrawipour
- Joanna Kulas
- Klaudia Kocielek
- Pawel Migdal
- Mohamed Arafkas
- Tanja Khosrawipour
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Affiliations: Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50‑373 Wroclaw, Poland, Department of Orthopedic and Trauma Surgery, Ortho‑Klinik Dortmund, Dortmund D‑44263, Germany, Department of Environment, Hygiene and Animal Welfare, Wroclaw University of Environmental and Life Sciences, 50‑373 Wroclaw, Poland, Department of Plastic Surgery, Ortho‑Klinik Dortmund, Dortmund D‑44263, Germany, Department of Surgery, Division of Colorectal Surgery, University of California, Irvine, Orange, CA 92868, USA
Published online on: September 5, 2019 https://doi.org/10.3892/mco.2019.1917
Pages: 483-487
Copyright: © Mikolajczyk et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present ex vivo study was performed to analyze the impact of high intensity ultrasound (HIUS) on penetration depth and particle stability of liposomal doxorubicin (LD) on the peritoneal surface. Fresh post mortem swine peritoneum was cut into proportional sections and subjected to a previously established ex vivo model of pressurized intraperitoneal aerosol chemotherapy (PIPAC). Samples were treated with 50 ml NaCl (0.9%) containing 3 mg LD via PIPAC or lavage. In both groups, half of the samples received additional HIUS treatment. Samples treated via PIPAC were covered with a 30‑mm‑thick abdominal muscle wall tissue, fatty tissue and skin, followed by transcutaneous HIUS. Samples administered with LD via lavage received close‑range contact HIUS. Doxorubicin tissue penetration was measured using fluorescence microscopy on frozen sections. Liposomal integrity on peritoneal surfaces was measured via electron microscopy (EM). Mean penetration rates of doxorubicin were significantly higher with HIUS in combination with PIPAC or lavage compared with PIPAC alone (P<0.001) or lavage alone (P<0.00001). LD was not detected on the peritoneal surface via EM analysis in either group following HIUS. The present data suggested that HIUS may be a feasible application that can facilitate the release of doxorubicin from its liposomal envelope. HIUS was effective in both close‑range, in contact with the samples, and through the abdominal wall. The present approach may be used in the future for both endoscopic and open lavage of the peritoneal cavity with LD in intraperitoneal chemotherapeutic applications such as hyperthermic intraperitoneal chemotherapy or PIPAC.

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1	Solass W, Kerb R, Mürdter T, Giger-Pabst U, Strumberg D, Tempfer C, Zieren J, Schwab M and Reymond MA: Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: First evidence for efficacy. Ann Surg Oncol. 21:553–559. 2014. View Article : Google Scholar : PubMed/NCBI
2	Göhler D, Khosrawipour V, Khosrawipour T, Diaz-Carballo D, Falkenstein TA, Zieren J, Stintz M and Giger-Pabst U: Technical description of the microinjection pump (MIP^®) and granulometric characterization of the aerosol applied for pressurized intraperitoneal aerosol chemotherapy (PIPAC). Surg Endosc. 31:1778–1784. 2017. View Article : Google Scholar : PubMed/NCBI
3	Khosrawipour V, Khosrawipour T, Kern AJ, Osma A, Kabakci B, Diaz-Carballo D, Förster E, Zieren J and Fakhrian K: Distribution pattern and penetration depth of doxorubicin after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a postmortem swine model. J Cancer Res Clin Oncol. 142:2275–2280. 2016. View Article : Google Scholar : PubMed/NCBI
4	Khosrawipour V, Khosrawipour T, Falkenstein TA, Diaz-Carballo D, Förster E, Osma A, Adamietz IA, Zieren J and Fakhrian K: Evaluating the effect of micropump© position, internal pressure and doxorubicin dosage on efficacy of pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in an ex vivo model. Anticancer Res. 36:4595–4600. 2016. View Article : Google Scholar : PubMed/NCBI
5	Khosrawipour V, Khosrawipour T, Diaz-Carballo D, Förster E, Zieren J and Giger-Pabst U: Exploring the spatial drug distribution pattern during pressurized intraperitoneal aerosol chemotherapy (PIPAC). Ann Surg Oncol. 23:1220–1224. 2016. View Article : Google Scholar : PubMed/NCBI
6	Khosrawipour T, Schubert J, Khosrawipour V, Chaudhry H, Grzesiak J, Arafkas M and Mikolajczyk A: Particle stability and structure on the peritoneal surface in pressurized intra-peritoneal aerosol chemotherapy (PIPAC) analysed by electron microscopy: First evidence of a new physical concept for PIPAC. Oncol Lett. 17:4921–4927. 2019.PubMed/NCBI
7	Mikolajczyk A, Khosrawipour V, Schubert J, Grzesiak J, Chaudhry H, Pigazzi A and Khosrawipour T: Effect of liposomal doxorubicin pressurized intra-peritoneal aerosol chemotherapy (PIPAC). J Cancer. 9:4301–4305. 2018. View Article : Google Scholar : PubMed/NCBI
8	Khosrawipour V, Khosrawipour T, Hedayat-Pour Y, Diaz-Carballo D, Bellendorf A, Böse-Riberio H, Mücke R, Mohanaraja N, Adamitz IA and Fakhrian K: Effect of whole abdominal irradiation on penetration depth of doxorubicin in normal tissue after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a post-mortem swine model. Anticancer Res. 37:1677–1680. 2017. View Article : Google Scholar : PubMed/NCBI
9	Khosrawipour V, Bellendorf A, Khosrawipour C, Hedayat-Pour Y, Diaz-Carballo D, Förster E, Mücke R, Kabakci B, Adamietz IA and Fakhrian K: Irradiation does not increase the penetration depth of doxorubicin in normal tissue after pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in an ex vivo model. In Vivo. 30:593–597. 2016.PubMed/NCBI
10	Khosrawipour V, Giger-Pabst U, Khosrawipour T, Pour YH, Diaz-Carballo D, Förster E, Böse-Ribeiro H, Adamietz IA, Zieren J and Fakhrian K: Effect of irradiation on tissue penetration depth of doxorubicin after pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in a novel ex-vivo model. J Cancer. 7:910–914. 2016. View Article : Google Scholar : PubMed/NCBI
11	Harrison LE, Bryan M, Pliner L and Saunders T: Phase I trial of pegylated liposomal doxorubicin with hyperthermic intraperitoneal chemotherapy in patients undergoing cytoreduction for advanced intra-abdominal malignancy. Ann Surg Oncol. 15:1407–1413. 2008. View Article : Google Scholar : PubMed/NCBI
12	Salvatorelli E, De Tursi M, Menna P, Carella C, Massari R, Colasante A, Iacobelli S and Minotti G: Pharmacokinetics of pegylated liposomal doxorubicin administered by intraoperative hyperthermic intraperitoneal chemotherapy to patients with advanced ovarian cancer and peritoneal carcinomatosis. Drug Metab Dispos. 40:2365–2373. 2012. View Article : Google Scholar : PubMed/NCBI
13	Hirano K and Hunt CA: Lymphatic transport of liposome-encapsuled agents: Effect of liposome size following intraperitoneal administration. J Pharm Sci. 74:915–921. 1985. View Article : Google Scholar : PubMed/NCBI
14	Carron PL, Padilla M and Maurizi Balzan J: Nephrotic syndrome and acute renal failure during pegylated liposomal doxorubicin treatment. Hemodial Int. 18:846–847. 2014. View Article : Google Scholar : PubMed/NCBI
15	Ansari L, Shiezadeh F, Taherzadeh Z, Nikoofal-Sahlabadi S, Momtazi-Borojeni AA, Sahebkar A and Eslami S: The most prevalent side effects of pegylated liposomal doxorubicin monotherapy in women with metastatic breast cancer: A systemic review of clinical trials. Cancer Gene Ther. 24:189–193. 2017. View Article : Google Scholar : PubMed/NCBI
16	Rizzitelli S, Guistetto P, Faletto D, Delli Castelli D, Aime S and Terreno E: The release of Doxorubicin from liposomes monitores by MRI and triggered by a combination of US stimuli led to a complete tumor regression in a breast cancer mouse model. J Control Release. 230:57–63. 2016. View Article : Google Scholar : PubMed/NCBI
17	Lyon PC, Griffiths LF, Lee J, Chung D, Carlise R, Wu F, Middelton MR, Gleeson FV and Coussios CC: Clinical trial protocol for Tardox: A phase I study to investigate the feasibility of target release of lyso-thermosensitive liposomal doxorubicin (ThermoDox^®) using focused ultrasound in patients with liver tumors. J Ther Ultrasound. 5:282017. View Article : Google Scholar : PubMed/NCBI
18	Khosrawipour V, Diaz-Carballo D, Acikelli AH, Khosrawipour T, Falkenstein TA, Wu D, Zieren J and Giger-Pabst U: Erratum to: Cytotoxic effect of different treatment parameters in pressurized intraperitoneal aerosol chemotherapy (PIPAC) on the in vitro proliferation of human colonic cancer cells. World J Surg Oncol. 15:942017. View Article : Google Scholar : PubMed/NCBI
19	Khosrawipour V, Mikolajczyk A, Schubert J and Khosrawipour T: Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) via endoscopical microcatheter system. Anticancer Res. 38:3447–3452. 2018. View Article : Google Scholar : PubMed/NCBI
20	Flessner MF, Choi J, Credit K, Deverkadra R and Henderson K: Resistance of tumor intestinal pressure to the penetration of intraperitoneally delivered antibodies into metastatic ovarian tumors. Clin Cancer Res. 11:3117–3125. 2005. View Article : Google Scholar : PubMed/NCBI
21	Holzer AK, Katano K, Klomp LW and Howell SB: Cisplatin rapidly down-regulates its own influx transporter hCTR1 in cultured human ovarian carcinoma cells. Clin Cancer Res. 10:6744–6749. 2004. View Article : Google Scholar : PubMed/NCBI
22	Mikolajczyk A, Khosrawipour V, Schubert J, Plociennik M, Nowak K, Fahr C, Chaudhry H and Khosrawipour T: Feasibility and characteristics of pressurized aerosol chemotherapy (PAC) in the bladder as a therapeutical option in early-stage urinary bladder cancer. In Vivo. 32:1369–1372. 2018. View Article : Google Scholar : PubMed/NCBI
23	Schubert J, Khosrawipour V, Chaudhry H, Arafkas M, Knoefel WT, Pigazzi A and Khosrawipour T: Comparing the cytotoxicity of taurolidine, mitomycin C, and oxaliplatin on the proliferation of in vitro colon carcinoma cells following pressurized intra-peritoneal aerosol chemotherapy (PIPAC). World J Surg Oncol. 17:932019. View Article : Google Scholar : PubMed/NCBI
24	Mikolajczyk A, Khosrawipour V, Schubert J, Chaudhry H, Pigazzi A and Khosrawipour T: Particle stability during pressurized intra-peritoneal aerosol chemotherapy (PIPAC). Anticancer Res. 38:4645–4649. 2018. View Article : Google Scholar : PubMed/NCBI
25	Sharma P, Mehta M, Dhanjal DS, Kaur S, Gupta G, Singh H, Thangavelu L, Rajeshkumar S, Tambuwala M, Bakshi HA, et al: Emerging trends in the novel drug delivery approaches for the treatment of lung cancer. Chem Biol Interact. 309:1087202019. View Article : Google Scholar : PubMed/NCBI
26	Kai M, Ziemys A, Liu YT, Kojic M, Ferrari M and Yokoi K: Tumor site-dependent transport properties determine nanotherapeutics delivery and its efficacy. Transl Oncol. 12:1196–1205. 2019. View Article : Google Scholar : PubMed/NCBI
27	Lokerse WJM, Bolkestein M, Dalm SU, Eggermont AMM, de Jong M, Grüll H and Koning GA: Comparing the therapeutic potential of thermosensitive liposomes and hyperthermia in two distinct subtypes of breast cancer. J Control Release. 258:34–42. 2017. View Article : Google Scholar : PubMed/NCBI
28	Falkenstein TA, Götze TO, Ouaissi M, Tempfer CB, Giger-Pabst U and Demtröder C: First clinical data of pressurized intraperitoneal aerosol chemotherapy (PIPAC) as salvage therapy for peritoneal metastatic biliary tract cancer. Anticancer Res. 38:373–378. 2018.PubMed/NCBI
29	Khosrawipour T, Khosrawipour V and Giger-Pabst U: Pressurized intra peritoneal aerosol chemotherapy in patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma. PLoS One. 12:e01867092017. View Article : Google Scholar : PubMed/NCBI
30	Armstrong DK, Fleming GF, Markman M and Bailey HH: A phase I trial of intraperitoneal sustained-release paclitaxel microspheres (Paclimer) in recurrent ovarian cancer: A Gynecologic Oncology Group study. Gynecol Oncol. 103:391–396. 2006. View Article : Google Scholar : PubMed/NCBI
31	Sugiyama T, Kumagai S, Nishida T, Ushijima K, Matuso T, Yakushiji M, Hyon SH and Ikada Y: Experimental and clinical evaluation of cisplatin-containing microspheres as intraperitoneal chemotherapy for ovarial cancer. Anticancer Res. 18:2837–2842. 1998.PubMed/NCBI
32	Lyon PC, Gray MD, Mannaris C, Folkes LK, Stratford M, Campo L, Chung DYF, Scott S, Anderson M, Goldin R, et al: Safety and feasibility of ultrasound-triggered targeted drug delivery of doxorubicin from thermosensitive liposomes in liver tumours (TARDOX): A single-centre, open-label, phase 1 trial. Lancet Oncol. 19:1027–1039. 2018. View Article : Google Scholar : PubMed/NCBI
33	Besse HC, Bos C, Zandvliet MMJM, van der Wulff-Jacobs K, Moonen CTW and Deckers R: Triggered radiosensitizer delivery using thermosensitive liposomes and hyperthermia improves efficacy of radiotherapy: An in vitro proof of concept study. PLoS One. 13:e02040632018. View Article : Google Scholar : PubMed/NCBI