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Drug Delievery for Glioblastoma: History
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Subjects: Medicine, Research & Experimental | Oncology
Contributor: Elza Neelima Mathew

Glioblastoma multiforme (GBM) is the most lethal intrinsic brain tumor. Drug delivery to glioblastoma is challenging because of the molecular and cellular heterogeneity of the tumor, its infiltrative nature, and the blood–brain barrier (BBB). Applications of convection-enhanced delivery (CED), controlled-release systems, nanomaterial systems, peptide-based therapeutics, and focused ultrasound for drug delivery to GBM are discussed in this review.

  • Glioblastoma multiforme
  • Controlled-Release Systems
  • drug delievery

Molecular and cellular heterogeneity, GBM cell dispersal and the BBB are critical constraints limiting the efficacy of anti-GBM drug therapy. Applications of CED, controlled release systems, nanomaterial systems, peptide-based therapeutics and focused ultrasound for drug delivery to tumor enhancing survival with reduced toxicity in animal studies (Table 1). Despite currently available treatments, the highly invasive GBM continues to be a deadly disease without cure in patients. Therefore, clinical trials that combine currently available therapies with the novel drug delivery approaches discussed here may enhance the effectiveness of molecular therapeutics in GBM. 

Method of Drug Delivery

Specific Examples

Controlled release systems

Gliadel[1][2][3][4]

 

Biodegradable wafers for the combined delivery of temozolomide and carmustine [5]

 

Biodegradable polymer implants releasing rapamycin[6]

 

Carboxymethylcellulose biopolymer system delivering rhodamine B[7]

 

Hydrogel based co-delivery of paclitaxel and temozolomide[8]

Convection enhanced delivery

Temozolomide[9]

 

Carboplatin[10]

 

Iron oxide nanoparticles conjugated to epidermal growth factor receptor deletion mutant III antibody (EG-FRVIIIAb)/MRI-guided[11]

Nanomaterial Systems

Poly(ε-caprolactone) (PCL) based nanoparticle system to deliver the natural growth modulating tripeptide GHK (glycyl-L-histidyl-L-lysine)[12]

 

Nanobubble-based theranostic system consisting of intravenously administered iron-platinum nanoparticles loaded with doxorubicin and surface-functionalized with transferrin[13]

Peptide based therapeutics

Tumor targeting peptides delivering deliver the oncolytic virus VSVΔM51, in combination with gadolinium[14]

 

Self-assembled spherical nanoparticles containing a peptide probe (Cy5.5-SAPD-99mTc) with mitochondria targeting[15]

 

Peptide derivatives of rabies virus glycoproteins, RVG29 and RVG15-liposome, delivering anticancer chemotherapeutic docetaxel nanoparticles and paclitaxel-cholesterol[16][17]

 

WSW (also called PhrCACET1) peptide fused to paclitaxel nanosuspensions[18]

 

Use of polydopamine (PDA)-coated zein-curcumin nanoparticles functionalized with the peptide G23[19]

 

Dual peptide nanocomplex created by combining SynB3 (a cell penetration peptide) with PVGLIG (an MMP-2 sensitive peptide) and paclitaxel[20]

Focused ultrasound

Temozolomide[21]

 

BCNU[22]

 

Liposomal O6-(4-bromothenyl)guanine (O6BTG)[23]

 

Liposome-encapsulated doxorubicin[24]

 

Cisplatin conjugated gold nanoparticles[25]

 

Trastzumab[26]

This entry is adapted from the peer-reviewed paper 10.3390/ijms23031711

References

  1. Chiara Bastiancich; P. Danhier; V. Préat; Anticancer drug-loaded hydrogels as drug delivery systems for the local treatment of glioblastoma. Journal of Controlled Release 2016, 243, 29-42, 10.1016/j.jconrel.2016.09.034.
  2. Andrew J. Sawyer; Joseph M. Piepmeier; W. Mark Saltzman; New Methods for Direct Delivery of Chemotherapy for Treating Brain Tumors. The Yale journal of biology and medicine 2007, 79, 141-152, .
  3. Jiangbing Zhou; Kofi-Buaku Atsina; Benjamin T. Himes; Garth W. Strohbehn; W. Mark Saltzman; Novel Delivery Strategies for Glioblastoma. The Cancer Journal 2011, 18, 89-99, 10.1097/ppo.0b013e318244d8ae.
  4. Eilam Yeini; Paula Ofek; Nitzan Albeck; Daniel Rodriguez Ajamil; Lena Neufeld; Anat Eldar‐Boock; Ron Kleiner; Daniella Vaskovich; Shani Koshrovski‐Michael; Sahar Israeli Dangoor; et al. Targeting Glioblastoma: Advances in Drug Delivery and Novel Therapeutic Approaches. Advanced Therapeutics 2020, 4, 2000124, 10.1002/adtp.202000124.
  5. Tovi Shapira-Furman; Riccardo Serra; Noah Gorelick; Marisol Doglioli; Valentina Tagliaferri; Arba Cecia; Michael Peters; Awanish Kumar; Yakir Rottenberg; Robert Langer; et al. Biodegradable wafers releasing Temozolomide and Carmustine for the treatment of brain cancer. Journal of Controlled Release 2018, 295, 93-101, 10.1016/j.jconrel.2018.12.048.
  6. Betty Tyler; Scott Wadsworth; Violette Recinos; Vivek Mehta; Ananth Vellimana; Khan Li; Joel Rosenblatt; Hiep Do; Gary L. Gallia; I.-M. Siu; et al. Local delivery of rapamycin: a toxicity and efficacy study in an experimental malignant glioma model in rats. Neuro-Oncology 2011, 13, 700-709, 10.1093/neuonc/nor050.
  7. E Dluska; A Markowska-Radomska; A Metera; M Ordak; Multiple Emulsions as a Biomaterial-based Delivery System for the Controlled Release of an Anti-cancer Drug. Journal of Physics: Conference Series 2020, 1681, 012021, 10.1088/1742-6596/1681/1/012021.
  8. Mengnan Zhao; Elia Bozzato; Nicolas Joudiou; Sina Ghiassinejad; Fabienne Danhier; Bernard Gallez; Véronique Préat; Codelivery of paclitaxel and temozolomide through a photopolymerizable hydrogel prevents glioblastoma recurrence after surgical resection. Journal of Controlled Release 2019, 309, 72-81, 10.1016/j.jconrel.2019.07.015.
  9. Julio Enríquez Pérez; Jan Kopecky; Edward Visse; Anna Darabi; Peter Siesjö; Convection-enhanced delivery of temozolomide and whole cell tumor immunizations in GL261 and KR158 experimental mouse gliomas. BMC Cancer 2020, 20, 1-12, 10.1186/s12885-019-6502-7.
  10. Joshua L. Wang; Rolf F. Barth; Robert Cavaliere; Vinay K. Puduvalli; Pierre Giglio; Russell R. Lonser; J. Bradley Elder; Phase I trial of intracerebral convection-enhanced delivery of carboplatin for treatment of recurrent high-grade gliomas. PLoS ONE 2020, 15, e0244383, 10.1371/journal.pone.0244383.
  11. Costas G. Hadjipanayis; Revaz Machaidze; Milota Kaluzova; Liya Wang; Albert J. Schuette; Hongwei Chen; Xinying Wu; Hui Mao; EGFRvIII Antibody–Conjugated Iron Oxide Nanoparticles for Magnetic Resonance Imaging–Guided Convection-Enhanced Delivery and Targeted Therapy of Glioblastoma. Cancer Research 2010, 70, 6303-6312, 10.1158/0008-5472.can-10-1022.
  12. Yasemin Budama-Kilinc; Serda Kecel-Gunduz; Rabia Cakir-Koc; Bahar Aslan; Bilge Bicak; Yagmur Kokcu; Aysen E. Ozel; Sevim Akyuz; Structural Characterization and Drug Delivery System of Natural Growth-Modulating Peptide Against Glioblastoma Cancer. International Journal of Peptide Research and Therapeutics 2021, 27, 1-14, 10.1007/s10989-021-10229-5.
  13. Ming-Hsien Chan; William Chen; Chien-Hsiu Li; Chih-Yeu Fang; Yu-Chan Chang; Da-Hua Wei; Ru-Shi Liu; Michael Hsiao; An Advanced In Situ Magnetic Resonance Imaging and Ultrasonic Theranostics Nanocomposite Platform: Crossing the Blood–Brain Barrier and Improving the Suppression of Glioblastoma Using Iron-Platinum Nanoparticles in Nanobubbles. ACS Applied Materials & Interfaces 2021, 13, 26759-26769, 10.1021/acsami.1c04990.
  14. Jennifer J. Rahn; Xueqing Lun; Selina K. Jorch; Xiaoguang Hao; Chitra Venugopal; Parvez Vora; Bo Young Ahn; Liane Babes; Mana M. Alshehri; J. Gregory Cairncross; et al. Development of a peptide-based delivery platform for targeting malignant brain tumors. Biomaterials 2020, 252, 120105, 10.1016/j.biomaterials.2020.120105.
  15. Syed Faheem Askari Rizvi; Samiah Shahid; Shuai Mu; Haixia Zhang; Hybridization of tumor homing and mitochondria-targeting peptide domains to design novel dual-imaging self-assembled peptide nanoparticles for theranostic applications. Drug Delivery and Translational Research 2021, n/a, 1-12, 10.1007/s13346-021-01066-6.
  16. Hongchen Hua; Xuemei Zhang; Hongjie Mu; Qingqing Meng; Ying Jiang; Yiyun Wang; Xiaoyan Lu; Aiping Wang; Sha Liu; Yaping Zhang; et al. RVG29-modified docetaxel-loaded nanoparticles for brain-targeted glioma therapy. International Journal of Pharmaceutics 2018, 543, 179-189, 10.1016/j.ijpharm.2018.03.028.
  17. Xin Xin; Wei Liu; Zhe-Ao Zhang; Ying Han; Ling-Ling Qi; Ying-Ying Zhang; Xin-Tong Zhang; Hong-Xia Duan; Li-Qing Chen; Ming-Ji Jin; et al. Efficient Anti-Glioma Therapy Through the Brain-Targeted RVG15-Modified Liposomes Loading Paclitaxel-Cholesterol Complex. International Journal of Nanomedicine 2021, 16, 5755-5776, 10.2147/ijn.s318266.
  18. Yueyue Fan; Yuexin Cui; Wenyan Hao; Mengyu Chen; Qianqian Liu; Yuli Wang; Meiyan Yang; Zhiping Li; Wei Gong; Shiyong Song; et al. Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma. Bioactive Materials 2021, 6, 4402-4414, 10.1016/j.bioactmat.2021.04.027.
  19. Huaiying Zhang; Winant L. van Os; Xiaobo Tian; Guangyue Zu; Laís Ribovski; Reinier Bron; Jeroen Bussmann; Alexander Kros; Yong Liu; Inge S. Zuhorn; et al. Development of curcumin-loaded zein nanoparticles for transport across the blood–brain barrier and inhibition of glioblastoma cell growth. Biomaterials Science 2021, 9, 7092-7103, 10.1039/d0bm01536a.
  20. Dan Hua; Lida Tang; Weiting Wang; Shengan Tang; Lin Yu; Xuexia Zhou; Qian Wang; Cuiyun Sun; Cuijuan Shi; Wenjun Luo; et al. Improved Antiglioblastoma Activity and BBB Permeability by Conjugation of Paclitaxel to a Cell‐Penetrative MMP‐2‐Cleavable Peptide. Advanced Science 2020, 8, 2001960, 10.1002/advs.202001960.
  21. Kuo-Chen Wei; Po-Chun Chu; Hay-Yan Jack Wang; Chiung-Yin Huang; Pin-Yuan Chen; Hong-Chieh Tsai; Yu-Jen Lu; Pei-Yun Lee; I-Chou Tseng; Li-Ying Feng; et al. Focused Ultrasound-Induced Blood–Brain Barrier Opening to Enhance Temozolomide Delivery for Glioblastoma Treatment: A Preclinical Study. PLoS ONE 2013, 8, e58995, 10.1371/journal.pone.0058995.
  22. Hao-Li Liu; Mu-Yi Hua; Pin-Yuan Chen; Po-Chun Chu; Chia-Hsin Pan; Hung-Wei Yang; Chiung-Yin Huang; Jiun-Jie Wang; Tzu-Chen Yen; Kuo-Chen Wei; et al. Blood-Brain Barrier Disruption with Focused Ultrasound Enhances Delivery of Chemotherapeutic Drugs for Glioblastoma Treatment. Radiology 2010, 255, 415-425, 10.1148/radiol.10090699.
  23. Alexandros Papachristodoulou; Rea Deborah Signorell; Beat Werner; Davide Brambilla; Paola Luciani; Mustafa Cavusoglu; Joanes Grandjean; Manuela Silginer; Markus Rudin; Ernst Martin; et al. Chemotherapy sensitization of glioblastoma by focused ultrasound-mediated delivery of therapeutic liposomes. Journal of Controlled Release 2018, 295, 130-139, 10.1016/j.jconrel.2018.12.009.
  24. Lisa H. Treat; Nathan McDannold; Natalia Vykhodtseva; Yongzhi Zhang; Karen Tam; Kullervo Hynynen; Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI-guided focused ultrasound. International Journal of Cancer 2007, 121, 901-907, 10.1002/ijc.22732.
  25. Daniel Coluccia; Carlyn A. Figueiredo; Megan YiJun Wu; Alexandra N. Riemenschneider; Roberto Diaz; Amanda Luck; Christian Smith; Sunit Das; Cameron Ackerley; Meaghan O’Reilly; et al. Enhancing glioblastoma treatment using cisplatin-gold-nanoparticle conjugates and targeted delivery with magnetic resonance-guided focused ultrasound. Nanomedicine: Nanotechnology, Biology and Medicine 2018, 14, 1137-1148, 10.1016/j.nano.2018.01.021.
  26. Ying Meng; Raymond M. Reilly; Rossanna C. Pezo; Maureen Trudeau; Arjun Sahgal; Amit Singnurkar; James Perry; Sten Myrehaug; Christopher B. Pople; Benjamin Davidson; et al. MR-guided focused ultrasound enhances delivery of trastuzumab to Her2-positive brain metastases. Science Translational Medicine 2021, 13, eabj4011, 10.1126/scitranslmed.abj4011.
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