Immobilization of Coacervate Microcapsules in Multilayer Sodium Alginate Beads for Efficient Oral Anticancer Drug Delivery

Abstract

We have designed and evaluated coacervate microcapsules-immobilized multilayer sodium alginate beads (CMs-M-ALG-Beads) for oral drug delivery. The CMs-M-ALG-Beads were prepared by immobilization of doxorubicin hydrochloride (DOX) loaded chitosan/carboxymethyl coacervate microcapsules (DOX:CS/CMCS-CMs) in the core and layers of the multilayer sodium alginate beads. The obtained CMs-M-ALG-beads exhibited layer-by-layer structure and rough surface with many nanoscale particles. The swelling characteristic and drug release results indicated that 4-layer CMs-M-ALG-Beads possessed favorable gastric acid tolerance (the swelling rate <5%, the cumulative drug release rate <3.8%). In small intestine, the intact DOX:CS/CMCS-CMs were able to rapidly release from CMs-M-ALG-Beads with the dissolution of ALG matrix. Ex vivo intestinal mucoadhesive and permeation showed that CMs-M-ALG-Beads exhibited continued growth for P(app) values of DOX, which was 1.07-1.15 folds and 1.28-1.38 folds higher than DOX:CS:CMCS-CMs in rat jejunum and ileum, respectively, demonstrating that CMs-M-ALG-Beads were able to enhance the absorption of DOX by controlled releasing DOX:CS/CMCS-CMs and prolonging the contact time between the DOX:CS/CMCS-CMs and small intestinal mucosa.

Multilayer sodium alginate beads with porous core containing chitosan based nanoparticles for oral delivery of anticancer drug

“…Nanoparticles immobilized multilayer sodium alginate beads (NPs-M-ALG-Beads) were prepared by external ionic gelation and Layer-by-Layer (LBL) method, according to Feng [7], which was divided into two processes (Scheme 1). Before the tiny hole dropping process, 5 mL of DOX:CS/CMCS-NPs (1 mg/mL) was sonicated for 5 min, Power 30%.…”

“…To improve oral bioavailability of conventional anticancer drugs, nanoparticles immobilized multilayer sodium alginate beads (NPs-M-Beads) were successfully developed by dropping aqueous chitosan/carboxymethyl chitosan nanoparticles blended with alginate (ALG) into CaCl 2 solution in our recent study [7]. The crosslinking between −COO − groups on ALG and Ca 2+ occurred from external of ALG matrix to form the compact core of multilayer bead.…”

Coacervate delivery systems for proteins and small molecule drugs

“…This method was employed using unmodified chitosan as the polycation to deliver doxorubicin in an oral formulation that slowly released it within the GI tract, significantly increasing its intestinal absorption and bioavailability in the blood [26]. The group went on to encapsulate the coacervate beads within sodium alginate shells for further stabilization and protection in the low pH gastric environment [27]. …”

Recent progress in preparation and agricultural application of microcapsules

“…Due to its good prosperities of nontoxicity, biocompatibility, and biodegradability, sodium alginate is one of the most studied materials and widely used as carrier materials of drugs (Braccini & Pérez, 2001;Qi et al, 2006;Sikorski et al, 2007). Additionally, it is also approved by the US Food and Drug Administration as a "generally regarded as safe (GRAS)" compound; more attention has been paid to its application as a drug microcapsule carrier materials (Feng et al, 2014). When sodium alginate encounters a divalent cation such as Ca 2+ , Ca 2+ can displace Na + to form a calcium alginate gel, which exhibiting more potent strength and elasticity.…”