Mucoadhesive paclitaxel-loaded chitosan-poly (isobutyl cyanoacrylate) core-shell nanocapsules containing copaiba oil designed for oral drug delivery

Abstract

The development of drug delivery systems for potent anticancer drugs like paclitaxel remains a challenger. The aim of this work was to study the mucoadhesive properties of paclitaxelloaded chitosan-poly (isobutyl cyanoacrylate) core-shell nanocapsules designed for oral drug delivery. Using an experimental design approach, the nanocapsules were produced and, then, physicochemically characterized. Mucoadhesion assays were performed in-vitro by the aggregation test with mucin and ex-vivo, in Ussing Chamber, using freshly excised rat intestinal mucosa. [3H]-paclitaxel dosages were carried out by liquid scintillation. Paclitaxel-loaded nanocapsules showed a mean hydrodynamic diameter of 470 nm with low polydispersity index and spherical form. Encapsulation efficiency and drug loading of paclitaxel were 74 ± 1% and 1.70 ± 0.02%, respectively. After drying, nanocapsules could be redispersed with no changes on their nanostructure. Dispersions of nanocapsules were stable in simulated gastric medium for 120 min, and after six months of storage at 4°C. They showed interesting mucoadhesive properties with mucins and good association (9 %) with the intestinal mucosa of the rat. Taking together, results from the present work are encouraging to pursue the development of chitosan-coated nanocapsules for oral delivery of paclitaxel as new treatment for cancer with possible synergetic anticancer effect with the therapeutically active components found in copaiba oil.

Polymeric Nanocapsules as Nanotechnological Alternative for Drug Delivery System: Current Status, Challenges and Opportunities

“…However, there is little discussion regarding the quantitative measurement of the polymeric shell of nanocapsules in most of studies; only few examples can be here reported. The main characterization method of the thickness is observation via transmission electron microscopy (TEM) [ 47 , 148 ]. For example, a 10-nm polymeric shell has been qualitatively estimated by TEM from argon oil/oleoyl polyoxylglycerides/Eudragit ® RS nanocapsules [ 176 ].…”

“…In this case, to store nanocapsules into dried form is generally preferable to improve the stability of nanocapsules and also prolong the store term [ 183 ]. Moreover, to adapt preparations of particular pharmaceutical dosage forms, such as oral tablet, it is necessary to manufacture the polymeric nanocapsules suspension into dry state for further preservation and usage [ 129 , 148 , 184 ]. Spray drying as one of the common drying method has been applied for recovery of nanocapsules into solid dry state.…”

Development of Metronidazole Loaded Chitosan Nanoparticles Using QbD Approach—A Novel and Potential Antibacterial Formulation

“…These characteristics include: slight burst release of drug in the early phase; easy permeability; resistance to degradation; hydrophobicity; high surface charge; high drug loading; nontoxic nature; high binding as well as deep permeating ability through mucous membrane owing to their nanosize [ 10 , 11 , 12 , 13 ]. Several polymers such as alginate and chitosan (CH) [ 14 ] have been exploited not only for their mucoadhesive effect in GI but also for discovering their probable effectiveness in the colon milieu.…”

“…CH is a cationic polysaccharide, which rapidly affixes to mucous membrane with a negative surface charge [ 14 ]. It is a biodegradable polymer and exhibits minimum toxicity, which make it an ideal carrier for the delivery of several drugs [ 15 ].…”

Optimization and Evaluation of Poly(lactide-co-glycolide) Nanoparticles for Enhanced Cellular Uptake and Efficacy of Paclitaxel in the Treatment of Head and Neck Cancer

“…Paclitaxel (PTX) is a diterpenoid pseudoalkaloid anticancer drug extracted from the Pacific Yew tree Taxus brevifolia [ 6 ]. Its chemotherapeutic effect is associated with its ability to bind to tubulin promoting microtubule assembly, stabilizing the existing microtubules and enhancing the action of tubulin dimers, therefore inhibiting their disassembly.…”