title: Hydrophilic drug encapsulation in shell-core microcarriers by two stage polyelectrolyte complexation method.
abstract: In this study a protocol exploiting the combination of the ultrasonic atomization and the complexation between polyelectrolytes was developed to efficiently encapsulate a hydrophilic chemotherapeutic agent essentially used in the treatment of colon cancer, 5-fluorouracil, in enteric shell-core alginate-based microcarriers. The atomization assisted by ultrasound allowed to obtain small droplets by supplying low energy and avoiding drug degradation. In particular microcarriers were produced in a home-made apparatus where both the core (composed of alginate, drug, and Pluronic F127) and shell (composed of only alginate) feed were separately sent to the coaxial ultrasonic atomizer where they were nebulized and placed in contact with the complexation bulk. With the aim to obtain microstructured particles of alginate encapsulating 5-fluorouracil, different formulations of the first complexation bulk were tested; at last an emulsion made of a calcium chloride aqueous solution and dichloromethane allowed to reach an encapsulation efficiency of about 50%. This result can be considered very interesting considering that in literature similar techniques gave 5-fluorouracil encapsulation efficiencies of about 10%. Since a single complexation stage was not able to assure microcarriers gastroresistance, the formulation of a second complexation bulk was evaluated. The solution of cationic and pH-insoluble Eudragit® RS 100 in dichloromethane was chosen as bulk of second-stage complexation obtaining good enteric properties of shell-core microcarriers, i.e. a 5-FU cumulative release at pH 1 (simulating gastric pH) lower than 35%. The formation of interpolyelectrolyte complex (IPEC) between countercharged polymers and the chemical stability of 5-FU in microcarriers were confirmed by FTIR analysis, the presence of an amorphous dispersion of 5-FU in prepared microparticles was also confirmed by DSC. Finally, shell-core enteric coated microcarriers encapsulating 5-fluorouracil were used to prepare tablets, which can be potentially used as oral administration dosage systems for their 5-fluorouracil slower release.
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Dalmoro
authors.affiliation: Department of Pharmaceutical, Analytical and Toxicological Chemistry, Kazan State Medical University, Butlerov Street 49, 420012 Kazan, Russian Federation.
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Sitenkov
authors.affiliation: Department of Industrial Engineering, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Cascone
authors.affiliation: Department of Industrial Engineering, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lamberti
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy. Electronic address: aabarba@unisa.it.
authors.forename: Anna Angela
authors.initials: AA
authors.lastname: Barba
authors.affiliation: Department of Pharmaceutical, Analytical and Toxicological Chemistry, Kazan State Medical University, Butlerov Street 49, 420012 Kazan, Russian Federation.
authors.forename: Rouslan I
authors.initials: RI
authors.lastname: Moustafine
mesh_terms: D000464:Alginates / Q000737:chemistry; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D005472:Fluorouracil / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D020442:Poloxamer / Q000737:chemistry; D000071228:Polyelectrolytes / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D013607:Tablets
chemical_list: D000464:Alginates; D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D006603:Hexuronic Acids; D000071228:Polyelectrolytes; D011109:Polymethacrylic Acids; D013607:Tablets; D020442:Poloxamer; C038300:methylmethacrylate-methacrylic acid copolymer; D020723:Glucuronic Acid; D005472:Fluorouracil
keywords: 5-Fluorouracil; 5-Fluorouracil (PubChem CID: 3385); Calcium chloride (PubChem CID: 5284359); Eudragit(®) E100 (PubChem CID: 107676); Eudragit(®) RL100 (PubChem CID: 104804); Eudragit(®) RS100 (PubChem CID: 104931); Hydrophilic drug; Pluronic F127 (PubChem CID: 24751); Polyelectrolyte complexation; Shell-core microparticles; Sodium alginate (PubChem CID: 5102882); Ultrasonic atomization