TY - JOUR
T1 - Extending Drug Release from Implants via Transcutaneous Refilling with Solid Therapeutics
AU - Di Trani, Nicola
AU - Pons-Faudoa, Fernanda P.
AU - Sizovs, Antons
AU - Shelton, Kathryn A.
AU - Marzinke, Mark A.
AU - Nehete, Pramod N.
AU - Grattoni, Alessandro
N1 - Funding Information:
N.D.T. and F.P.P.-F. contributed equally to this work. The authors thank Dr. Corrine Ying Xuan Chua and Dr. Jesus Paez-Mayorga of the Houston Methodist Research Institute for manuscript proofreading and Gulsah Malgir for her help in the filter characterization experiment. The authors also thank Dr. Roberto Arduino for the useful discussions and Luke Segura, Elizabeth Lindemann, Dana Salazar, and Dr. Greg Wilkerson from the Michale E. Keeling Center for Comparative medicine and Research at UTMDACC for support in NHP studies, and Bharti Nehete for plasma isolation. TAF was provided by Gilead Sciences, Inc. Funding: This work was supported by funding from Houston Methodist Research Institute (A.G.) and the National Institutes of Health National Institute of Allergy and Infectious Diseases (R01AI120749; A.G.). The development of the nanochannel membrane used in the studies was funded by the National Institutes of Health National Institute of General Medical Sciences (R01GM127558; A.G.).
Funding Information:
N.D.T. and F.P.P.‐F. contributed equally to this work. The authors thank Dr. Corrine Ying Xuan Chua and Dr. Jesus Paez‐Mayorga of the Houston Methodist Research Institute for manuscript proofreading and Gulsah Malgir for her help in the filter characterization experiment. The authors also thank Dr. Roberto Arduino for the useful discussions and Luke Segura, Elizabeth Lindemann, Dana Salazar, and Dr. Greg Wilkerson from the Michale E. Keeling Center for Comparative medicine and Research at UTMDACC for support in NHP studies, and Bharti Nehete for plasma isolation. TAF was provided by Gilead Sciences, Inc. Funding: This work was supported by funding from Houston Methodist Research Institute (A.G.) and the National Institutes of Health National Institute of Allergy and Infectious Diseases (R01AI120749; A.G.). The development of the nanochannel membrane used in the studies was funded by the National Institutes of Health National Institute of General Medical Sciences (R01GM127558; A.G.).
Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2022/2
Y1 - 2022/2
N2 - Long-acting (LA) implantable drug delivery systems (IDDS) offer an effective approach for the management or prevention of chronic conditions by sustained parenteral therapeutic administration. LA IDDS can and improve adherence to treatment regimens by minimizing dosing frequency. However, their clinical deployment is challenged by factors such as poor drug loading capacity, which limit their lifespan and require repeated surgical replacement for continued therapy. To address these challenges, and by leveraging previous work on nanofluidic systems, a reservoir-based IDDS that enables transcutaneous refilling of solid drug formulations through minimally invasive needle injection is presented. With thousand-fold higher drug loading efficiency, the implant affords minimal volume and aspect ratio suitable for discrete subcutaneous deployment. Key parameters for clinical acceptability, namely implant safety, access port robustness, and refilling method were systematically evaluated. The implant and refilling procedure are studied in rats and nonhuman primates with therapeutics used clinically for type 2 diabetes and human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP). The ability to extend drug release and maintain equivalent pharmacokinetics (PK) profiles pre- and post-drug refilling is demonstrated. This technology presents a clinically viable LA approach to prolong drug release for lifelong prevention or management of chronic conditions.
AB - Long-acting (LA) implantable drug delivery systems (IDDS) offer an effective approach for the management or prevention of chronic conditions by sustained parenteral therapeutic administration. LA IDDS can and improve adherence to treatment regimens by minimizing dosing frequency. However, their clinical deployment is challenged by factors such as poor drug loading capacity, which limit their lifespan and require repeated surgical replacement for continued therapy. To address these challenges, and by leveraging previous work on nanofluidic systems, a reservoir-based IDDS that enables transcutaneous refilling of solid drug formulations through minimally invasive needle injection is presented. With thousand-fold higher drug loading efficiency, the implant affords minimal volume and aspect ratio suitable for discrete subcutaneous deployment. Key parameters for clinical acceptability, namely implant safety, access port robustness, and refilling method were systematically evaluated. The implant and refilling procedure are studied in rats and nonhuman primates with therapeutics used clinically for type 2 diabetes and human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP). The ability to extend drug release and maintain equivalent pharmacokinetics (PK) profiles pre- and post-drug refilling is demonstrated. This technology presents a clinically viable LA approach to prolong drug release for lifelong prevention or management of chronic conditions.
KW - implantable drug delivery devices
KW - long-term drug delivery
KW - transcutaneous refill
UR - http://www.scopus.com/inward/record.url?scp=85121721903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121721903&partnerID=8YFLogxK
U2 - 10.1002/adtp.202100214
DO - 10.1002/adtp.202100214
M3 - Article
C2 - 35815229
AN - SCOPUS:85121721903
SN - 2366-3987
VL - 5
JO - advanced therapeutics
JF - advanced therapeutics
IS - 2
M1 - 2100214
ER -