Original ArticleNovel biodegradable poly(gamma-glutamic acid)–amphotericin B complexes show promise as improved amphotericin B formulations
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Degradation of high molecular weight PGGA
In a typical alkaline hydrolysis reaction, PGGA of the free acid form (5 g, 34.45 mmol; 1500 kDa, Natto Biosciences) was dissolved in aqueous sodium bicarbonate (50 mL, 67.60 mM). The solution was heated to 90 °C and NaOH (1.38 g, 34.45 mmol) was added. The solution was maintained at 90 °C for 6 h, and subsequently allowed to cool to room temperature. The pH of the solution was adjusted to 7.0 with HCl, and subsequently treated with Amberlite resin (50 g, IR-120 H+ type, 50 mesh,
Molecular weight determination by gel permeation chromatography (GPC)
The results of PGGA degradation are shown in Table 1. For the determination of MW of the PGGA, the specific refractive index (dn/dc) of the polymer was obtained from a plot of refractive index (IR) detector peak area versus the PGGA concentration (0-10 mg/mL) at a fixed volume (1 mL); the slope of which corresponded to the dn/dc value (0.0939) (Figure S1). The polymer MW was calculated using the Rayleigh equation:
Where R, K, C and M are the intensity of the scattered light, the optical
Discussion
Our goal was to develop an alternative AmB formulation that offers the best attributes of the approved AmB formulations, namely the high efficacy and low cost of the AmB-deoxycholate, along with improved safety profiles of the lipid based AmB formulations. Using the naturally-occurring and biodegradable polymer PGGA, we were able to synthesize non-covalently associated AmB/PGGA complexes of varying polymer molecular weights (55, 65 and 110 kDa). The preparation of the AmB/PGGA complexes
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Funding: We would like to thank Natto Biosciences for the kind donation of poly(gamma-glutamic acid) for this research.