Lamivudine and Zidovudine-Loaded Nanostructures: Green Chemistry Preparation for Pediatric Oral Administration

Abstract

Here, we report on the development of lipid-based nanostructures containing zidovudine (1 mg/mL) and lamivudine (0.5 mg/mL) for oral administration in the pediatric population, eliminating the use of organic solvents, which is in accordance with green chemistry principles. The formulations were obtained by ultrasonication using monoolein (MN) or phytantriol (PN), which presented narrow size distributions with similar mean particle sizes (~150 nm) determined by laser diffraction. The zeta potential and the pH values of the formulations were around -4.0 mV and 6.0, respectively. MN presented a slightly higher incorporation rate compared to PN. Nanoemulsions were obtained when using monoolein, while cubosomes were obtained when using phytantriol, as confirmed by Small-Angle X-ray Scattering. The formulations enabled drug release control and protection against acid degradation. The drug incorporation was effective and the analyses using an electronic tongue indicated a difference in palatability between the nanotechnological samples in comparison with the drug solutions. In conclusion, PN was considered to have the strongest potential as a novel oral formulation for pediatric HIV treatment.

Keywords: children; cubosomes; green chemistry; nanoemulsion; oral administration.

Figure 1

Thermograms of 3TC (A), AZT (B), monoolein (C), phytantriol (D), monoolein-based nanostructures—MN (E), phytantriol-based nanostructures—PN (F), poloxamer (G), physical mixture of MN formulation ingredients (H), and physical mixture of PN formulation ingredients (I). Lines: 10°C/50 min (green), 10 °C/100 min (blue), 10 °C/200 min (red).

Figure 2

Scanning electron microscopy images of cubosomes (A) and nanoemulsion (B).

Figure 3

Size D[4,3](V) (A), span(V) (B), zeta potential (C), pH (D), 3TC content (E), and AZT content (F) of formulations at times 0, 15, and 30 days under storage at room temperature. MN: monoolein-based nanostructures. PN: phytantriol-based nanostructures.

Figure 4

In vitro 3TC (A) and AZT (B) release profiles in water from FS, MN, and PN formulations. FS: free drug solution; MN: monoolein-based nanostructures; PN: phytantriol-based nanostructures.

Figure 5

UV–vis spectra obtained after the deposition of each bilayer for (A) PAH/PPS, (B) PAH/GO, (C) PEI/PSS, and (D) PEI/GO LbL films.

Figure 6

PCA graph obtained with the resistance data collected at the frequency of 1000 Hz for the drug solutions and the solutions used to mimic the basic tastes (A). Dendrogram obtained from the cluster analysis performed with electrical resistance data collected at the frequency of 1000 Hz (B). FS: free drug solution (lamivudine + zidovudine); MN: monoolein-based nanostructures; PN: phytantriol-based nanostructures.