Single-dose intraperitoneal delivery of FK506-encapsulated polymeric microspheres for the alleviation of murine colitis

Shiva Pathak; Shobha Regmi; Mahesh Raj Nepal; Prakash Shrestha; Jeong Uk Choi; Simmyung Yook; Jee-Heon Jeong

Journal of Industrial and Engineering Chemistry, Vol.91, 121-128, November, 2020

DOI10.1016/j.jiec.2020.07.041 Export Citation

Single-dose intraperitoneal delivery of FK506-encapsulated polymeric microspheres for the alleviation of murine colitis

Shiva Pathak^{1, 2}, Shobha Regmi^{1, 3}, Mahesh Raj Nepal¹, Prakash Shrestha¹, Jeong Uk Choi^{4, †}, Simmyung Yook^{5, †}, and Jee-Heon Jeong^{1, †}

¹College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea
²Division of Blood and Bone Marrow Transplantation, Stanford University School of Medicine, Stanford, CA 94305, United States, Korea
³Interventional and Regenerative Medicine, Stanford University School of Medicine, Palo Alto, CA 94304, United States, Korea
⁴Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
⁵College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea

E-mail:, ,

Based on the severity of the disease progression, the treatment of ulcerative colitis involves administration of single or multiple therapeutic agents. In refractory cases of ulcerative colitis, FK506 (FK) is the drug of choice in clinics. To maintain a long-term stable blood concentration of FK and to reduce its dosing frequency, we propose single-dose injection of FK-loaded biodegradable microspheres (FK-Ms). FK-Ms were intraperitoneally-injected into mice fed with dextran-sulfate sodium (DSS). Pharmacokinetics study revealed presence of FK in blood for over 20 days. The single intraperitoneal injection of the drug-loaded microspheres effectively alleviated DSS-induced murine colitis. Mechanistically, the single injection of FK-Ms inhibited the infiltration of T cells into colon and attenuated differentiation of T cells into interferon-γ secreting Th1 and interleukin-17A secreting Th17 cells in colon-draining mesenteric lymph nodes. Therefore, administration of prolonged-release type microspheres can be considered as an alternative for the effective treatment of inflammatory bowel diseases.

Keywords:Ulcerative colitis;Tacrolimus;PLGA microspheres;Intraperitoneal injection;Effector T cells

[References]

Head KA, Jurenka JS, Altern. Med. Rev., 8, 247 (2003)
Tamboli CP, Surg. Clin. N. Am., 87, 697 (2007)
Lightner AL, Clin. Transl. Gastroenterol., 8, e82 (2017)
Nolan A, Shaikh S, Sagedy H, Hawksworth J, Kroemer A, Fishbein T, Matsumoto C, Transplantation, 103, S129 (2019)
Kim KJ, Alam Z, Oh E, Hwang YH, Lee YK, Yun CO, Lee DY, J. Ind. Eng. Chem., 47, 202 (2017)
Ogata H, Matsui T, Nakamura M, Iida M, Takazoe M, Suzuki Y, Hibi T, Gut, 55, 1255 (2006)
Ibekwe VC, Liu F, Fadda HM, Khela MK, Evans DF, Parsons GE, Basit AE, J. Pharm. Sci., 95, 2760 (2006)
Patole VC, Pandit AP, J. Pharm. Investig., 48, 257 (2018)
Serra L, Domenech J, Peppas NA, Eur. J. Pharm. Biopharm., 71, 519 (2009)
Ashford M, Fell J, Attwood D, Sharma H, Woodhead P, J. Control. Release, 30, 225 (1994)
Sawarkar SP, Deshpande SG, Bajaj AN, Soni PS, Pandit P, Nikam VS, J. Pharm. Investig., 50, 173 (2020)
Wilson DS, Dalmasso G, Wang LX, Sitaraman SV, Merlin D, Murthy N, Nat. Mater., 9(11), 923 (2010)
Regmi S, Pathak S, Nepal MR, Shrestha P, Park J, Kim JO, Yong CS, et al., J. Control. Release, 316, 138 (2019)
Duwa R, Emami F, Lee SY, Jeong JH, Yook SM, J. Ind. Eng. Chem., 79, 261 (2019)
Bose RJC, Kim MW, Chang JH, Paulmurugan R, Moon JJ, Koh WG, Lee SH, Park HS, J. Ind. Eng. Chem., 77, 12 (2019)
Kim SN, Choi BH, Kim HK, Choy YB, J. Ind. Eng. Chem., 75, 86 (2019)
Schoubben A, Ricci M, Giovagnoli S, J. Pharm. Investig., 49, 381 (2019)
Blasi P, J. Pharm. Investig., 49, 337 (2019)
Pathak S, Gupta B, Poudel BK, Tran TH, Regmi S, Pham TT, Thapa RK, Kim MS, Yong CS, Kim JO, Jeong JH, Chem. Pharm. Bull., 64, 171 (2016)
Pathak S, Regmi S, Shrestha P, Choi I, Doh KO, Jeong JH, Small, 15, e19012 (2019)
Acharya S, Timilshina M, Jiang L, Neupane S, Choi DY, Park SW, Lee SY, Jeong BS, Kim JA, Nam TG, Chang JH, Sci. Rep., 8, 7799 (2018)
Houston SA, Cerovic V, Thomson C, Brewer J, Mowat AM, Milling S, Mucosal Immunol., 9, 468 (2016)
Pathak S, Regmi S, Gupta B, Poudel BK, Pham TT, Yong CS, Kim JO, Kim JR, Park MH, Bae YK, Yook S, Ahn CH, Jeong JH, Drug Deliv., 24, 1350 (2017)
Przepiorka D, Nash RA, Wingard JR, Zhu J, Maher RM, Fitzsimmons WE, Fay JW, Biol. Blood Marrow Transplant., 5, 94 (1999)
Khan MZI, Prebeg Z, Kurjakovic N, J. Control. Release, 58, 215 (1999)
Lamprecht A, Yamamoto H, Takeuchi H, Kawashima Y, J. Control. Release, 104, 337 (2005)
Meissner Y, Pellequer Y, Lamprecht A, Int. J. Pharm., 316, 138 (2006)
Nidhi, Rashid M, Kaur V, Hallan SS, Sharma S, Mishra N, Saudi Pharm. J., 24, 458 (2016)
Champion JA, Walker A, Mitragotri S, Pharm. Res., 25, 1815 (2008)
Beloqui A, Coco R, Alhouayek M, Solinis MA, Rodriguez-Gascon A, Muccioli GG, Preat V, Int. J. Pharm., 454, 775 (2013)
Wang JL, Gan YJ, Iqbal S, Jiang W, Yuan YY, Wang J, Biomater. Sci., 6, 1916 (2018)
Naeem M, Bae J, Oshi MA, Kim MS, Moon HR, Lee BL, Im E, Jung Y, Yoo JW, Int. J. Nanomed., 13, 1225 (2018)

[1] Head KA, Jurenka JS, Altern. Med. Rev., 8, 247 (2003)

[2] Tamboli CP, Surg. Clin. N. Am., 87, 697 (2007)

[3] Lightner AL, Clin. Transl. Gastroenterol., 8, e82 (2017)

[4] Nolan A, Shaikh S, Sagedy H, Hawksworth J, Kroemer A, Fishbein T, Matsumoto C, Transplantation, 103, S129 (2019)

[5] Kim KJ, Alam Z, Oh E, Hwang YH, Lee YK, Yun CO, Lee DY, J. Ind. Eng. Chem., 47, 202 (2017)

[6] Ogata H, Matsui T, Nakamura M, Iida M, Takazoe M, Suzuki Y, Hibi T, Gut, 55, 1255 (2006)

[7] Ibekwe VC, Liu F, Fadda HM, Khela MK, Evans DF, Parsons GE, Basit AE, J. Pharm. Sci., 95, 2760 (2006)

[8] Patole VC, Pandit AP, J. Pharm. Investig., 48, 257 (2018)

[9] Serra L, Domenech J, Peppas NA, Eur. J. Pharm. Biopharm., 71, 519 (2009)

[10] Ashford M, Fell J, Attwood D, Sharma H, Woodhead P, J. Control. Release, 30, 225 (1994)

[11] Sawarkar SP, Deshpande SG, Bajaj AN, Soni PS, Pandit P, Nikam VS, J. Pharm. Investig., 50, 173 (2020)

[12] Wilson DS, Dalmasso G, Wang LX, Sitaraman SV, Merlin D, Murthy N, Nat. Mater., 9(11), 923 (2010)

[13] Regmi S, Pathak S, Nepal MR, Shrestha P, Park J, Kim JO, Yong CS, et al., J. Control. Release, 316, 138 (2019)

[14] Duwa R, Emami F, Lee SY, Jeong JH, Yook SM, J. Ind. Eng. Chem., 79, 261 (2019)

[15] Bose RJC, Kim MW, Chang JH, Paulmurugan R, Moon JJ, Koh WG, Lee SH, Park HS, J. Ind. Eng. Chem., 77, 12 (2019)

[16] Kim SN, Choi BH, Kim HK, Choy YB, J. Ind. Eng. Chem., 75, 86 (2019)

[17] Schoubben A, Ricci M, Giovagnoli S, J. Pharm. Investig., 49, 381 (2019)

[18] Blasi P, J. Pharm. Investig., 49, 337 (2019)

[19] Pathak S, Gupta B, Poudel BK, Tran TH, Regmi S, Pham TT, Thapa RK, Kim MS, Yong CS, Kim JO, Jeong JH, Chem. Pharm. Bull., 64, 171 (2016)

[20] Pathak S, Regmi S, Shrestha P, Choi I, Doh KO, Jeong JH, Small, 15, e19012 (2019)

[21] Acharya S, Timilshina M, Jiang L, Neupane S, Choi DY, Park SW, Lee SY, Jeong BS, Kim JA, Nam TG, Chang JH, Sci. Rep., 8, 7799 (2018)

[22] Houston SA, Cerovic V, Thomson C, Brewer J, Mowat AM, Milling S, Mucosal Immunol., 9, 468 (2016)

[23] Pathak S, Regmi S, Gupta B, Poudel BK, Pham TT, Yong CS, Kim JO, Kim JR, Park MH, Bae YK, Yook S, Ahn CH, Jeong JH, Drug Deliv., 24, 1350 (2017)

[24] Przepiorka D, Nash RA, Wingard JR, Zhu J, Maher RM, Fitzsimmons WE, Fay JW, Biol. Blood Marrow Transplant., 5, 94 (1999)

[25] Khan MZI, Prebeg Z, Kurjakovic N, J. Control. Release, 58, 215 (1999)

[26] Lamprecht A, Yamamoto H, Takeuchi H, Kawashima Y, J. Control. Release, 104, 337 (2005)

[27] Meissner Y, Pellequer Y, Lamprecht A, Int. J. Pharm., 316, 138 (2006)

[28] Nidhi, Rashid M, Kaur V, Hallan SS, Sharma S, Mishra N, Saudi Pharm. J., 24, 458 (2016)

[29] Champion JA, Walker A, Mitragotri S, Pharm. Res., 25, 1815 (2008)

[30] Beloqui A, Coco R, Alhouayek M, Solinis MA, Rodriguez-Gascon A, Muccioli GG, Preat V, Int. J. Pharm., 454, 775 (2013)

[31] Wang JL, Gan YJ, Iqbal S, Jiang W, Yuan YY, Wang J, Biomater. Sci., 6, 1916 (2018)

[32] Naeem M, Bae J, Oshi MA, Kim MS, Moon HR, Lee BL, Im E, Jung Y, Yoo JW, Int. J. Nanomed., 13, 1225 (2018)