A simple way for targeted delivery of an antibiotic: In vitro evaluation of a nanoclay-based composite

Abstract

The sodium-modified form of fluorohectorite nanoclay (NaFh) is introduced as a potential drug carrier, demonstrating its ability for the controlled release of the broad-spectrum antibiotic Ciprofloxacin through in vitro tests. The new clay-drug composite is designed to target the local infections in the large intestine, where it delivers most of the incorporated drug thanks to its pH-sensitive behavior. The composite has been conceived to avoid the use of coating technology and to decrease the side-effects commonly associated to the burst-release of the ciprofloxacin at the stomach level. NaFh was obtained from lithium-fluorohectorite by ion exchange, and its lack of toxicity was demonstrated by in vivo studies. Ciprofloxacin hydrochloride (Cipro) was encapsulated into the clay at different values of the pH, drug initial concentration, temperature and time. Systematic studies by X-ray diffraction (XRD), infrared and visible spectrophotometry (FT-IR and UV-vis), and thermal analysis (TGA) indicated that the NaFh host exhibits a high encapsulation efficiency for Cipro, which reaches a 90% of the initial Cipro in solution at 65 oC, with initial concentration of drug in solution of 1.36 x 10−2 mol L-1 at acid pH. XRD revealed that a true intercalation of Cipro takes place between clay layers. TG showed an increased thermal stability of the drug when intercalated into the clay, as compared to the “free” Cipro. IR suggested a strong clay-Cipro interaction via ketone group, as well as the establishment of hydrogen bonds between the two materials. In vitro drug release tests revealed that NaFh is a potentially efficient carrier to deliver Cipro in the large intestine, where the release process is mediated by more than just one mechanism.

Synthesis and Characterization of Nanomaterial Based on Halloysite and Hectorite Clay Minerals Covalently Bridged

“…Furthermore, HNTs-Ht nanomaterial could be an alternative system for the simultaneous co-delivery of different antibacterial agents for the treatment of different patologies. It, indeed presents similar adsorption behavior of other systems commonly used, such as bentonite, fluorohectorite, montmorillonite, and hydroxyapatite, for the delivery of ciprofloxacin and silver ions [ 27 , 28 , 29 , 30 , 31 ].…”

Experimental methods to study clay minerals and perspective applications of Fluorohectorite

“…It has been demonstrated that the capture of CIPRO by FHt is more efficient at acidic than neutral environments, with FHt capturing up to 0.49 g of CIPRO per gram of FHt, and highly inefficient capture at alkaline conditions [52,56,57,58,59,60] . There is substantial evidence pointing out that the capture of APIs at low pH occurs mainly via cation exchange, with the drug molecules replacing the interlamellar cation and acting in its place to maintain the charge balance of the FHt particles [52,56,58] .…”

“…Despite CIPRO's capture ability at neutral environments, the higher efficacy in acidic conditions indicates that the ionic nature of the API is an important parameter to be considered when preparing the clay-drug composites [56] . Furthermore, release studies demonstrated that the drug release is slow, pH-dependent, controlled and thermally activated [52,58] * Regarding toxicity of FHt and FHt-drug composites, in vivo and in vitro studies demonstrated that FHt is not harmful, even when it has Li + as interlamellar cation [58,59] . Additionally, the effectiveness of FHt-CIPRO against important human pathogens, such as E. coli and P. aeruginosa, remained the same as the effectiveness of CIPRO alone.…”

Clay nanolayer encapsulation, evolving from origins of life to future technologies

“…There are several cases investigated and reported in the literature with respect to capturing and retention mechanisms for encapsulation of foreign molecules inside such clay interlayers ( Fig. 6), including H 2 O intercalation [12,13,[39][40][41][42][43][44][45][46], CO 2 capture and retention [36,[47][48][49][50][51], cation exchange [12,13,52], medical drug capture and release [12,13,39,[53][54][55][56][57][58][59], capture of surfactants [12,13,39,60,61], polymers [12,13,39,[62][63][64], or nanoparticles [65]. These encapsulation properties of clay nanolayered stacks are crucial for several engineering applications, e.g.…”