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Issue 3, 2019
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Tuning HIV drug release from a nanogel-based in situ forming implant by changing nanogel size

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Abstract

HIV is a global public health threat and requires life-long, daily oral dosing to effectively treat. This pill burden often results in poor adherence to the medications. An injectable in situ forming implant with tuneable drug release kinetics would allow patients to replace some of their daily pills with a single infrequent injection. In this work, we investigate how the size of poly(N-isopropylacrylamide) (polyNIPAm) nanogels influences the long-acting release behaviour of the HIV drug lopinavir from an in situ forming implant. Four sizes of polyNIPAm nanogels were prepared with mean diameters of 65, 160, 310 and 450 nm as characterised by dynamic light scattering. These nanogels all displayed synergistic dual stimuli responsive behaviour by aggregating only upon heating above 31 °C at physiological ionic strength. Mixing the nanogels with solid drug nanoparticles (SDNs) of lopinavir and exposing this concentrated dispersion to physiological temperature and ionic strength resulted in the in situ formation of nanocomposite implants. Three different loadings of the SDNs (33, 50 and 66% w/w) with each of the nanogels were prepared. The drug release behaviour and stability of these nanocomposite implants were then assessed in vitro over 360 hours. All samples displayed a single phase of drug release and application of the Ritger–Peppas equation indicated Fickian diffusion. Nanocomposites with the lowest loading of SDNs (33%) showed a linear relationship between nanogel diameter and the dissolution constant. These results show an attractive method for tuning the release of lopinavir from in situ loading implants with high drug loadings.

Graphical abstract: Tuning HIV drug release from a nanogel-based in situ forming implant by changing nanogel size

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Publication details

The article was received on 17 Jun 2018, accepted on 27 Nov 2018 and first published on 20 Dec 2018


Article type: Paper
DOI: 10.1039/C8TB01597J
Citation: J. Mater. Chem. B, 2019,7, 373-383
  • Open access: Creative Commons BY license
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    Tuning HIV drug release from a nanogel-based in situ forming implant by changing nanogel size

    A. R. Town, J. Taylor, K. Dawson, E. Niezabitowska, N. M. Elbaz, A. Corker, E. Garcia-Tuñón and T. O. McDonald, J. Mater. Chem. B, 2019, 7, 373
    DOI: 10.1039/C8TB01597J

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