Effects of Polymer Blending on the Performance of a Subcutaneous Biodegradable Implant for HIV Pre-Exposure Prophylaxis (PrEP)

被引:10
|
作者
Li, Linying [1 ]
Areson, Christine [1 ]
van der Straten, Ariane [2 ,3 ]
Johnson, Leah M. [1 ]
机构
[1] Engn Syst RTI Int, Durham, NC 27709 USA
[2] Univ Calif San Francisco, Ctr AIDS Prevent Studies, Dept Med, San Francisco, CA 94104 USA
[3] ASTRA Consulting, Kensington, CA 94708, Australia
关键词
poly(epsilon-caprolactone) (PCL); biodegradable polymer; polymer blends; HIV pre-exposure prophylaxis (PrEP); tenofovir alafenamide; subcutaneous implant; long-acting drug delivery; DRUG-RELEASE; COPOLYMERS; DELIVERY; POLY(EPSILON-CAPROLACTONE); CRYSTALLIZATION; CRYSTALLINITY; DESIGN; BLOCK; ACID;
D O I
10.3390/ijms22126529
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Long-acting (LA) HIV pre-exposure prophylaxis (PrEP) can mitigate challenges of adhering to daily or on-demand regimens of antiretrovirals (ARVs). We are developing a subcutaneous implant comprising polycaprolactone (PCL) for sustained delivery of ARVs for PrEP. Here we use tenofovir alafenamide (TAF) as a model drug. Previously, we demonstrated that the release rates of drugs are controlled by the implant surface area and wall thickness, and the molecular weight (MW) of PCL. Here, we further advance the implant design and tailor the release rates of TAF and the mechanical integrity of the implant through unique polymer blend formulations. In vitro release of TAF from the implant exhibited zero-order release kinetics for similar to 120 days. TAF release rates were readily controlled via the MW of the polymer blend, with PCL formulations of higher MW releasing the drug faster than implants with lower MW PCL. Use of polymer MW to tune drug release rates is partly explained by PCL crystallinity, as higher PCL crystalline material is often associated with a slower release rate. Moreover, results showed the ability to tailor mechanical properties via PCL blends. Blending PCL offers an effective approach for tuning the ARV release rates, implant duration, and integrity, and ultimately the biodegradation profiles of the implant.
引用
收藏
页数:18
相关论文
共 50 条
  • [1] A Subcutaneous Biodegradable Implant for Sustained Delivery of Tenofovir Alafenamide (TAF) for HIV Pre-exposure Prophylaxis (PrEP)
    Girouard, Natalie
    Johnson, Leah
    Luecke, Ellen
    Demkovich, Zach
    Jester, Teresa
    Li, Alice
    Johnson, Pafio
    van der Straten, Ariane
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 2018, 34 : 107 - 107
  • [2] Performance and Stability of Tenofovir Alafenamide Formulations within Subcutaneous Biodegradable Implants for HIV Pre-Exposure Prophylaxis (PrEP)
    Li, Linying
    Johnson, Leah M.
    Krovi, Sai Archana
    Demkovich, Zach R.
    van der Straten, Ariane
    [J]. PHARMACEUTICS, 2020, 12 (11) : 1 - 17
  • [3] HIV pre-exposure prophylaxis (PrEP)
    Tumarkin, Ethan
    Siedner, Mark J.
    Bogoch, Isaac I.
    [J]. BMJ-BRITISH MEDICAL JOURNAL, 2019, 364
  • [4] PrEP: pre-exposure prophylaxis for HIV prevention
    Page, Matthew
    Nicholls, Jane
    [J]. TRENDS IN UROLOGY & MENS HEALTH, 2018, 9 (04) : 22 - 24
  • [5] HIV pre-exposure prophylaxis (PrEP); [Pre-expositieprofylaxe tegen hiv (PrEP)]
    Hermanussen R.
    [J]. Huisarts en wetenschap, 2017, 60 (6) : 264 - 267
  • [6] Pre-exposure HIV prophylaxis (PrEP) background and controversies
    Zalewski, Bartlomiej M.
    Jablonska, Monika
    Mikula, Tomasz
    [J]. HIV & AIDS REVIEW, 2009, 8 (04): : 8 - 10
  • [7] State of the Science - HIV Pre-Exposure Prophylaxis (PrEP)
    Chariyalertsak, S.
    [J]. INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 2012, 16 : E9 - E10
  • [8] Pre-exposure prophylaxis (PrEP)
    Bradshaw, Helen
    [J]. HIV MEDICINE, 2021, 22 : 47 - 47
  • [9] PrEP Whores and HIV Prevention: The Queer Communication of HIV Pre-Exposure Prophylaxis (PrEP)
    Spieldenner, Andrew
    [J]. JOURNAL OF HOMOSEXUALITY, 2016, 63 (12) : 1685 - 1697
  • [10] Ambivalence and the biopolitics of HIV pre-exposure prophylaxis (PrEP) implementation
    Gaspar, Mark
    Salway, Travis
    Grace, Daniel
    [J]. SOCIAL THEORY & HEALTH, 2022, 20 (02) : 171 - 187