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Open AccessArticle

Cellulose Acetate Phthalate and Antiretroviral Nanoparticle Fabrications for HIV Pre-Exposure Prophylaxis

1
School of Pharmacy and Health Professions, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA
2
Department of Biology, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA
3
Dana-Farber Cancer Institute, Harvard University, Boston, MA 02215, USA
*
Author to whom correspondence should be addressed.
Polymers 2017, 9(9), 423; https://doi.org/10.3390/polym9090423
Received: 26 July 2017 / Revised: 1 September 2017 / Accepted: 4 September 2017 / Published: 7 September 2017
(This article belongs to the Special Issue Cellulose Nanomaterials)
To adequately reduce new HIV infections, development of highly effective pre-exposure prophylaxis (PrEP) against HIV infection in women is necessary. Cellulose acetate phthalate (CAP) is a pH sensitive polymer with HIV-1 entry inhibitory properties. Dolutegravir (DTG) is an integrase strand transfer inhibitor with potent antiretroviral activity. DTG delivered in combination with CAP may significantly improve current PrEP against HIV. In the present study, the development of DTG-loaded CAP nanoparticles incorporated in thermosensitive (TMS) gel at vaginal pH 4.2 and seminal fluid pH 7.4 is presented as proof-of-concept for improved PrEP. Water–oil–in–water homogenization was used to fabricate DTG-loaded CAP nanoparticles (DTG–CAP–NPs). Size, polydispersity, and morphological analyses illustrate that DTG–CAP–NPs were smooth and spherical, ≤200 nm in size, and monodispersed with a polydispersity index PDI ≤ 0.2. The drug encapsulation (EE%) and release profile of DTG–CAP–NPs was determined by HPLC analysis. The EE% of DTG in DTG–CAP–NPs was evaluated to be ~70%. The thermal sensitivity of the TMS gel was optimized and the pH dependency was evaluated by rheological analysis. DTG release studies in TMS gel revealed that DTG–CAP–NPs were stable in TMS gel at pH 4.2 while DTG–CAP–NPs in TMS gel at pH 7.4 rapidly release DTG (≥80% release within 1 h). Cytotoxicity studies using vaginal cell lines revealed that DTG–CAP–NPs were relatively non-cytotoxic at concentration <1 µg/mL. Confocal microscopic studies illustrate that ≥98% cells retained DTG–CAP–NPs intracellularly over seven days. Antiretroviral drug loaded nanocellulose fabrications in TMS gel delivered intravaginally may enhance both microbicidal and antiretroviral drug efficacy and may present a novel option for female PrEP against HIV. View Full-Text
Keywords: cellulose acetate phthalate; anti-retroviral; nanoparticles; thermosensitive gel; HIV; pre-exposure prophylaxis cellulose acetate phthalate; anti-retroviral; nanoparticles; thermosensitive gel; HIV; pre-exposure prophylaxis
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MDPI and ACS Style

Mandal, S.; Khandalavala, K.; Pham, R.; Bruck, P.; Varghese, M.; Kochvar, A.; Monaco, A.; Prathipati, P.K.; Destache, C.; Shibata, A. Cellulose Acetate Phthalate and Antiretroviral Nanoparticle Fabrications for HIV Pre-Exposure Prophylaxis. Polymers 2017, 9, 423.

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