Dendrimeric micelles composed of polyamidoamine dendrimer-peptidecholesterol conjugates as drug carriers for the treatment of melanoma and bacterial infection

Le Thi Thuy; Namyoung Kang; Minyoung Choi; Minhyung Lee; Joon Sig Choi

Journal of Industrial and Engineering Chemistry, Vol.114, 361-376, October, 2022

DOI10.1016/j.jiec.2022.07.026 Export Citation

Dendrimeric micelles composed of polyamidoamine dendrimer-peptidecholesterol conjugates as drug carriers for the treatment of melanoma and bacterial infection

Le Thi Thuy, Namyoung Kang, Minyoung Choi, Minhyung Lee^{1, †}, and Joon Sig Choi^†

Department of Biochemistry, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea
¹Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea

E-mail:,

Skin cancer is a serious health concern posing an economic burden. Phytochemicals isolated from plants have attracted the attention of researchers as potential therapeutic agents against skin cancer. Paclitaxel and curcumin are effective anticancer agents. However, their poor solubility in aqueous solutions results in low bioavailability, limiting their therapeutic applications. In this study, we developed dendrimeric micelles to encapsulate paclitaxel and curcumin for the treatment of melanoma. The antibacterial activity of curcumin-loaded dendrimeric micelles was evaluated. Dendrimeric micelles were prepared using PAMAM dendrimers conjugated with histidine-arginine dipeptides and cholesterol (PHRC). Different amounts of cholesterol (6 % or 23 %) were conjugated to the surface of PAMAM dendrimer generation 2 derivatives (PAMAM G2-HR) to evaluate the effects of cholesterol on the drug encapsulation efficiency and bioactivity. The critical aggregation concentration (CAC) value of PHRC6 and PHRC23 was 0.14 mg/mL and 0.09 mg/mL, respectively. The size of the dendrimeric micelles was confirmed using dynamic light scattering (DLS). Furthermore, the cytotoxicity of PHRC amphiphiles was measured in B16F10 melanoma cells. Both PHRC6 and PHRC23 were combined with TPGS to prepare functional mixed dendrimeric micelles, including PHRC6/TPGS and PHRC23/TPGS. The encapsulation efficiency was higher for curcumin than paclitaxel (80.2 % and 76.3 % for curcumin and 30.7 % and 38.2 % for paclitaxel in PHRC6/TPGS and PHRC23/TPGS, respectively). Based on these results, PHRC/TPGS dendrimeric micelles displayed a high potential for the nano-formulation of hydrophobic drugs and good bioavailability and bioactivity against skin cancer.

Keywords:Paclitaxel;Curcumin;Dendrimeric micelles;Melanoma;PAMAM dendrimer

[References]

Fijalkowska M, Koziej M, Antoszewski B, Sci Rep-Uk, 11 (2021)
Kalal BS, Upadhya D, Pai VR, Oncol Rev, 11, 326 (2017)
Newman DJ, Cragg GM, J. Nat. Prod., 83, 770 (2020)
AlQathama A, Prieto JM, Nat. Prod. Rep., 32, 1170 (2015)
Chinembiri TN, du Plessis LH, Gerber M, Hamman JH, du Plessis J, Molecules, 19, 11679 (2014)
Ijaz S, Akhtar N, Khan MS, Hameed A, Irfan M, Arshad MA, et al., Biomed. Pharm., 103, 1643 (2018)
Haddad R, Alrabadi N, Altaani B, Li TL, Polymers-Basel, 14 (2022)
Mekkawy AI, Naguib YW, Alhaj-Suliman SO, Wafa EI, Ebeid K, Acri T, et al., Int. J. Pharm., 606, 120876 (2021)
Bharadwaj R, Das PJ, Pal P, Mazumder B, Drug. Dev. Ind. Pharm., 42, 1482 (2016)
Sharifi-Rad J, Quispe C, Patra JK, Singh YD, Panda MK, Das G, et al., Oxid. Med. Cell. Longev, 2021 (2021)
Nawara HM, Afify SM, Hassan G, Zahra MH, Seno A, Seno M, Biomedicines, 9 (2021)
Orr GA, Verdier-Pinard P, McDaid H, Horwitz SB, Oncogene, 22, 7280 (2003)
Giordano A, Tommonaro G, Nutrients, 11 (2019)
Wang BL, Liu XX, Teng Y, Yu T, Chen JL, Hu YZ, et al., Oncotarget, 8, 108624 (2017)
Zhou H, Beevers CS, Huang S, Curr. Drug. Targets, 12, 332 (2011)
Shishodia S, Biofactors, 39, 37 (2013)
Naranjo-Duran AM, Quintero-Quiroz J, Rojas-Camargo J, Ciro-Gomez GL, Sci Rep-Uk, 11 (2021)
Elisia I, Nakamura H, Lam V, Hofs E, Cederberg R, Cait J, et al., Plos One, 11 (2016)
Mishra A, Pradhan D, Biswasroy P, Kar B, Ghosh G, Rath G, J. Drug Deliv. Sci. Technol., 65 (2021)
Bas S, Soucek MD, Polym. J., 44, 1087 (2012)
Hibino M, Tanaka K, Ouchi M, Terashima T, Macromolecules, 55, 178 (2022)
Li C, Tho CC, Galaktionova D, Chen X, Kral P, Mirsaidov U, Nanoscale, 11, 2299 (2019)
Ren LL, Nie JF, Wei J, Li YN, Yin J, Yang XL, et al., Drug Deliv., 28, 2024 (2021)
Mallick S, Song SJ, Bae Y, Choi JS, Int. J. Biol. Macromol., 132, 451 (2019)
Golombek SK, May JN, Theek B, Appold L, Drude N, Kiessling F, et al., Adv. Drug Deliv. Rev., 130, 17 (2018)
Yang CL, Wu TT, Qi Y, Zhang ZP, Theranostics, 8, 464 (2018)
Wu Y, Chu Q, Tan S, Zhuang X, Bao Y, Wu T, et al., Int. J. Nanomedicine, 10, 5219 (2015)
Fraguas-Sanchez AI, Lozza I, Torres-Suarez AI, Cancers, 14 (2022)
Araujo RV, Santos SDS, Ferreira EI, Giarolla J, Molecules, 23 (2018)
Chawla M, Kaushik RD, Manila JS, Sci Rep-Uk, 10, 21977 (2020)
Singh J, Chawla M, Kaushik RD, J. Ind. Chem. Soc., 99, 100408 (2022)
Gajbhiye V, Kumar PV, Sharma A, Agarwal A, Asthana A, Jain NK, Ind. J. Pharm. Sci., 70, 431 (2008)
Kheraldine H, Rachid O, Habib AM, Al Moustafa AE, Benter IF, Akhtar S, Adv. Drug Deliv. Rev., 178 (2021)
Tiwari N, Osorio-Blanco ER, Sonzogni A, Esporrín-Ubieto D, Wang H, Calderón M, Angew. Chem.-Int. Edit., 61, e2021079 (2022)
Kim G, Piao C, Oh J, Lee M, Nanoscale, 10, 8503 (2018)
Fana M, Gallien J, Srinageshwar B, Dunbar GL, Rossignol J, Int. J. Nanomed, 15, 2789 (2020)
Pfisterer SG, Peranen J, Ikonen E, Curr. Opin. Lipidol, 27, 282 (2016)
Mayengbam SS, Singh A, Pillai AD, Bhat MK, Transl Oncol, 14 (2021)
Wu H, Zhu L, Torchilin VP, Biomaterials, 34, 1213 (2013)
Tomeh MA, Hadianamrei R, Zhao XB, Int. J. Mol. Sci., 20 (2019)
Kabir MT, Rahman MH, Akter R, Behl T, Kaushik D, Mittal V, et al., Biomacromolecules, 11 (2021)
Kim YS, Ahn Y, Hong MH, Joo SY, Kim KH, Sohn IS, et al., J. Cardiovasc Pharm, 50, 41 (2007)
Winnicka K, Wroblewska M, Wieczorek P, Sacha PT, Tryniszewska EA, Molecules, 18, 8607 (2013)
Ullah F, Ayaz M, Sadiq A, Ullah F, Hussain I, Shahid M, et al., Appl. Sci-Basel, 10 (2020)

[Related Articles]

[1] Fijalkowska M, Koziej M, Antoszewski B, Sci Rep-Uk, 11 (2021)

[2] Kalal BS, Upadhya D, Pai VR, Oncol Rev, 11, 326 (2017)

[3] Newman DJ, Cragg GM, J. Nat. Prod., 83, 770 (2020)

[4] AlQathama A, Prieto JM, Nat. Prod. Rep., 32, 1170 (2015)

[5] Chinembiri TN, du Plessis LH, Gerber M, Hamman JH, du Plessis J, Molecules, 19, 11679 (2014)

[6] Ijaz S, Akhtar N, Khan MS, Hameed A, Irfan M, Arshad MA, et al., Biomed. Pharm., 103, 1643 (2018)

[7] Haddad R, Alrabadi N, Altaani B, Li TL, Polymers-Basel, 14 (2022)

[8] Mekkawy AI, Naguib YW, Alhaj-Suliman SO, Wafa EI, Ebeid K, Acri T, et al., Int. J. Pharm., 606, 120876 (2021)

[9] Bharadwaj R, Das PJ, Pal P, Mazumder B, Drug. Dev. Ind. Pharm., 42, 1482 (2016)

[10] Sharifi-Rad J, Quispe C, Patra JK, Singh YD, Panda MK, Das G, et al., Oxid. Med. Cell. Longev, 2021 (2021)

[11] Nawara HM, Afify SM, Hassan G, Zahra MH, Seno A, Seno M, Biomedicines, 9 (2021)

[12] Orr GA, Verdier-Pinard P, McDaid H, Horwitz SB, Oncogene, 22, 7280 (2003)

[13] Giordano A, Tommonaro G, Nutrients, 11 (2019)

[14] Wang BL, Liu XX, Teng Y, Yu T, Chen JL, Hu YZ, et al., Oncotarget, 8, 108624 (2017)

[15] Zhou H, Beevers CS, Huang S, Curr. Drug. Targets, 12, 332 (2011)

[16] Shishodia S, Biofactors, 39, 37 (2013)

[17] Naranjo-Duran AM, Quintero-Quiroz J, Rojas-Camargo J, Ciro-Gomez GL, Sci Rep-Uk, 11 (2021)

[18] Elisia I, Nakamura H, Lam V, Hofs E, Cederberg R, Cait J, et al., Plos One, 11 (2016)

[19] Mishra A, Pradhan D, Biswasroy P, Kar B, Ghosh G, Rath G, J. Drug Deliv. Sci. Technol., 65 (2021)

[20] Bas S, Soucek MD, Polym. J., 44, 1087 (2012)

[21] Hibino M, Tanaka K, Ouchi M, Terashima T, Macromolecules, 55, 178 (2022)

[22] Li C, Tho CC, Galaktionova D, Chen X, Kral P, Mirsaidov U, Nanoscale, 11, 2299 (2019)

[23] Ren LL, Nie JF, Wei J, Li YN, Yin J, Yang XL, et al., Drug Deliv., 28, 2024 (2021)

[24] Mallick S, Song SJ, Bae Y, Choi JS, Int. J. Biol. Macromol., 132, 451 (2019)

[25] Golombek SK, May JN, Theek B, Appold L, Drude N, Kiessling F, et al., Adv. Drug Deliv. Rev., 130, 17 (2018)

[26] Yang CL, Wu TT, Qi Y, Zhang ZP, Theranostics, 8, 464 (2018)

[27] Wu Y, Chu Q, Tan S, Zhuang X, Bao Y, Wu T, et al., Int. J. Nanomedicine, 10, 5219 (2015)

[28] Fraguas-Sanchez AI, Lozza I, Torres-Suarez AI, Cancers, 14 (2022)

[29] Araujo RV, Santos SDS, Ferreira EI, Giarolla J, Molecules, 23 (2018)

[30] Chawla M, Kaushik RD, Manila JS, Sci Rep-Uk, 10, 21977 (2020)

[31] Singh J, Chawla M, Kaushik RD, J. Ind. Chem. Soc., 99, 100408 (2022)

[32] Gajbhiye V, Kumar PV, Sharma A, Agarwal A, Asthana A, Jain NK, Ind. J. Pharm. Sci., 70, 431 (2008)

[33] Kheraldine H, Rachid O, Habib AM, Al Moustafa AE, Benter IF, Akhtar S, Adv. Drug Deliv. Rev., 178 (2021)

[34] Tiwari N, Osorio-Blanco ER, Sonzogni A, Esporrín-Ubieto D, Wang H, Calderón M, Angew. Chem.-Int. Edit., 61, e2021079 (2022)

[35] Kim G, Piao C, Oh J, Lee M, Nanoscale, 10, 8503 (2018)

[36] Fana M, Gallien J, Srinageshwar B, Dunbar GL, Rossignol J, Int. J. Nanomed, 15, 2789 (2020)

[37] Pfisterer SG, Peranen J, Ikonen E, Curr. Opin. Lipidol, 27, 282 (2016)

[38] Mayengbam SS, Singh A, Pillai AD, Bhat MK, Transl Oncol, 14 (2021)

[39] Wu H, Zhu L, Torchilin VP, Biomaterials, 34, 1213 (2013)

[40] Tomeh MA, Hadianamrei R, Zhao XB, Int. J. Mol. Sci., 20 (2019)

[41] Kabir MT, Rahman MH, Akter R, Behl T, Kaushik D, Mittal V, et al., Biomacromolecules, 11 (2021)

[42] Kim YS, Ahn Y, Hong MH, Joo SY, Kim KH, Sohn IS, et al., J. Cardiovasc Pharm, 50, 41 (2007)

[43] Winnicka K, Wroblewska M, Wieczorek P, Sacha PT, Tryniszewska EA, Molecules, 18, 8607 (2013)

[44] Ullah F, Ayaz M, Sadiq A, Ullah F, Hussain I, Shahid M, et al., Appl. Sci-Basel, 10 (2020)