Interaction of polyelectrolyte-shell cubosomes with serum albumin for triggering drug release in gastrointestinal cancer.

Nano-structured and functionalized materials for encapsulation, transport, targeting and controlled release of drugs are of high interest to overcome low bioavailability in oral administration. We develop lipid-based cubosomes, which are surface-functionalized with biocompatible chitosan-N-arginine and alginate, displaying internal liquid crystalline structures. Polyelectrolyte-shell (PS) cubosomes have pH-responsive characteristics profitable for oral delivery. The obtained PScubosomes can strongly interact with serum albumin, a protein which is released in the stomach under gastric cancer conditions. An effective thermodynamic PScubosome-protein interaction was characterized at pH 2.0 and 7.4 by isothermal titration calorimetry at 37 °C. A high increment of the albumin conformation transition temperature was evidenced by differential scanning calorimetry upon incubation with PScubosomes. The performed structural studies by synchrotron small-angle X-ray scattering (SAXS) revealed essential alterations in the internal liquid crystalline topology of the nanocarriers including an Im3m to Pn3m transition and a reduction of the cubic lattice parameters. The PScubosome nanoparticle interaction with serum albumin, leading to inner structural changes in a range of temperatures, promoted the release of water from the cubosomal nanochannels. Altogether, the results revealed effective interactions of the PScubosomes with albumin under simulated gastrointestinal pH conditions and suggested promising nanocarrier characteristics for triggered oral drug release.

Efficient Treatment of Fish Intestinal Parasites Applying a Membrane-Penetrating Oral Drug Delivery Nanoparticle.

Nanodelivery of drugs aims to ensure drug stability in the face of adverse biochemical conditions in the course of administration, concomitant with appropriate pharmacological action provided by delivery at the targeted site. In this study, the application potential of a nanoparticle produced with biopolymers chitosan-N-arginine and alginate as an oral drug delivery material is evaluated. Both macromolecules being weak polyelectrolytes, the nanoparticle presents strong thermodynamic interactions with a biological model membrane consisting of a charged lipid liposome bilayer, leading to membrane disruption and membrane penetration of the nanoparticles in ideal conditions of pH corresponding to the oral route. The powder form of the nanoparticle was obtained by lyophilization and with a high percentage of entrapment of the anthelmintic drug praziquantel. In vivo studies were conducted with oral administration to Corydoras schwartzi fish with high intensity of intestinal parasites infection. The in vivo experiments confirmed the mucoadhesive and revealed membrane-penetrating properties of the nanoparticle by translocating the parasite cyst, which provided target drug release and reduction of over 97% of the fish intestinal parasites. Thus, it was evidenced that the nanoparticle was effective in transporting and releasing the drug to the target, providing an efficient treatment.