NDLI: Hyaluronidase-Sensitive Nanoparticle Templates for Triggered Release of HIV/AIDS Microbicide In Vitro

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Hyaluronidase-Sensitive Nanoparticle Templates for Triggered Release of HIV/AIDS Microbicide In Vitro

Content Provider	Springer Nature Link
Author	Agrahari, Vivek Zhang, Chi Zhang, Tao Li, Wenjing Gounev, Todor K. Oyler, Nathan A. Youan, Bi Botti C.
Copyright Year	2013
Abstract	This study was designed to test the hypothesis that a triggered release of a topical microbicide (tenofovir) from hyaluronic acid nanoparticles (HA-NPs) can be achieved under the influence of hyaluronidase (HAase) enzyme. A fractional factorial experimental design was used to examine the factors [molar concentrations of adipic acid dihydrazide (X$_{1}$) and 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (X$_{2}$), volume of acetone (X$_{3}$) and reaction time (X$_{4}$)] influencing the responses, Y$_{1}$; particle mean diameter: PMD (nanometers: nm), Y$_{2}$; polydispersity index: PDI and Y$_{3}$; zeta (ζ) potential: (millivolts). The amide bond formation between HA and ADH after cross-linking was confirmed by FT-IR and $^{13}$C-NMR analyses. These NPs were also characterized for cytotoxicity on a human vaginal epithelial cell line and L. crispatus. When formulated with factors X$_{1}$; 2.49 mM, X$_{2}$; 9.96 mM, X$_{3}$; 60 mL, X$_{4}$; 6 h, HA-NPs exhibited a spherical shape with PMD, PDI, ζ potential, encapsulation efficiency, and drug loading of 70.6 ± 4.1 nm, 0.07 ± 0.02, −38.2 ± 2.8 mV, 51.8 ± 2.4% w/w and 26.1 ± 1.2% w/w, respectively, (n = 3). Unlike for HA based gel, HAase significantly triggered the drug release and HA degradation from the NPs after 24 h (∼90% w/w and 65% w/w, respectively); whereas, in its absence, these values were ∼39% w/w and 26% w/w, respectively. The NPs were non-cytotoxic to human vaginal VK2/E6E7, End1/E6E7 cells and Lactobacillus crispatus. These data highlight the potential of HAase-sensitive HA-NPs templates for the controlled and vaginal delivery of anti-HIV/AIDS microbicides.
Starting Page	181
Ending Page	193
Page Count	13
File Format	PDF
ISSN	12341234
Journal	The AAPS Journal
Volume Number	16
Issue Number	2
e-ISSN	15507416
Language	English
Publisher	Springer US
Publisher Date	2013-12-17
Publisher Institution	American Association of Pharmaceutical Scientists
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Biochemistry Biotechnology Pharmacy
Content Type	Text
Resource Type	Article

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