Formulation and Rheology of the Antimicrobial and
Temperature-Responsive Hydrogel Delivery System
AgNPs-PVP was chosen to formulate the hydrogel delivery system due to
its superior antimicrobial efficacy compared to unprotected AgNPs.
AgNPs-PVP was added to an 18%(w/v) P407 aqueous solution to formulate
the antimicrobial and temperature-responsive hydrogel, with
concentration of the AgNPs-PVP (Ag:PVP ratio of 2:1) in the hydrogel
varied in the range of 0-100 µM. The resulting formulation was referred
to as XµM[AgNPs-PVP]-18%[P407], where X indicated the
concentration of Ag (Figure 6A).
As discussed previously, P407 was used here due to its reverse thermal
gelation properties, i.e., the AgNPs-PVP-containing formulation could
flow readily into the middle ear space during administration, and then
gel promptly at 37°C to ensure sustained antimicrobial effect. The
concentration of P407, i.e., 18% (w/v), was selected based on our prior
experience, which led to a gelation temperature close to 37°C and
sufficient
gel
strength to sustain drug delivery over the 7 – 10 day-course of
treatment 51.
Linear oscillatory shear rheology of the AgNPs-PVP-containing hydrogel
formulations demonstrated that introduction of the nanotherapeutics at
concentrations at or below 100 µM did not jeopardize the desirable
reverse thermal gelation. For each formulation, storage (G′) and loss
(G′′) moduli were quantified in the temperature range of 20 – 40ºC; and
gelation (i.e., the transition from a liquid formulation to a solid gel)
was defined as the point where G′ was greater than G′′ by 2kPa. Without
the nanotherapeutics, the formulation containing 18%[P407] had a
gelation temperature of 25 ºC, and G′ and G′′ of 12.27 ± 0.42 kPa and
4.22 ± 0.21 kPa at 37ºC (Figure 6B). At the AgNPs-PVP concentration of
50 µM, the hydrogel formulation demonstrated virtually unchanged
gelation temperature of 24 ºC, and G′ and G′′ of 12.29 ± 0.19 kPa and
4.63 ± 0.14 kPa respectively at 37ºC (Figure 6C). With 100 µM AgNPs-PVP,
the gelation temperature remained at 24 ºC, with G′ and G′′ values
increased to 14.41 ± 1.91 kPa and 6.07 ± 0.50 kPa at 37ºC (Figure 6D),
which was likely a result of the entanglement between PVP and P407
chains. Gelation did not occur for the formulation of
200µM[AgNPs-PVP]-18%[P407] and G′ was reduced to 5.29 ± 0.66
kPa, merely half of that of 18%[P407] (Figure 6E). This could be
attributed to the inability for P407 chains to form micelles and/or for
micelles to pack into a solid gel due to the substantial presence of PVP
chains. Values of the gelation temperatures and storage/loss moduli were
summarized in a table (Figure 6F).