Dextrin-Based Nanohydrogels for Rokitamycin Prolonged Topical Delivery

Abstract

Macrolides are widely used antibiotics with a broad spectrum of activity. The development of drug carriers to deliver this type of antibiotics has attracted much research. The present study aims at developing new swellable dextrin-based nanohydrogels for the topical delivery of rokitamycin, as model macrolide. Rokitamycin is a synthetic analogous of macrolides with advantageous characteristics as far as bacterial uptake and post-antibiotic effect are concerned. It is also indicated for the treatment of severe infections caused by Acanthamoeba and for topical infections. The nanohydrogels have been prepared from two types of cross-linked polymers obtained by using β-cyclodextrin or Linecaps^® was provided by the Roquette Italia SPA (Cassano Spinola, Al, Italy) as building blocks. The cross-linked polymers have been then formulated into aqueous nanosuspensions refined and tuned to achieve the incorporation of the drug. Cross-linked β-cyclodextrin (β-CD) and Linecaps^® (LC) polymers formed dextrin-based nanohydrogels with high swelling degree and mucoadhesion capability. Rokitamycin was loaded into the nanohydrogels displaying an average size around 200 nm with negative surface charge. In vitro kinetic profiles of free and loaded drug in nanohydrogels were compared at two pH levels. Interestingly, a sustained and controlled release was obtained at skin pH level due to the high degree of swelling and a pH responsiveness possibly. The results collected suggest that these nanohydrogels are promising for the delivery of rokitamycin and may pave the way for the topical delivery of other macrolide antibiotics.

Keywords: cyclodextrin; formulation; linecaps; nanohydrogels; nanosponges; rokitamycin.

Figure 1

Chemical structure of Rokitamycin (C₄₂H₆₉NO₁₅).

Figure 2

Helical structure of amylose Linecaps^®.

Figure 3

Scheme of the synthetic procedures to obtain (a) β-CD PYRO and (b) LC PYRO NSs.

Figure 4

Schematic representation of the nanohydrogel formulation.

Figure 5

FTIR analysis of RK, blank NSs, physical mixtures, and loaded NSs indicated the principal differences.

Figure 6

DSC thermograms RK, blank NSs, and RK-loaded NSs. Insert. TGA thermogram of Rokitamycin.

Figure 7

SEM images of (a) blank β-CD PYRO (1:4), (b) RK-loaded β-CD PYRO (1:4), (c) blank LC PYRO (1:4), and (d) RK-loaded LC PYRO (1:4).

Figure 8

In vitro release profiles of RK-loaded NSs in pH 5.5–7.4 the first 4 h.

Figure 9

Release of RK-loaded NSs in pH 5.5–7.4 after 28 h.