Hydrophilic drug encapsulation in shell-core microcarriers by two stage polyelectrolyte complexation method

被引:38
作者
Dalmoro, Annalisa [1 ]
Sitenkov, Alexander Y. [2 ]
Cascone, Sara [3 ]
Lamberti, Gaetano [3 ]
Barba, Anna Angela [1 ]
Moustafine, Rouslan I. [2 ]
机构
[1] Univ Salerno, Dept Pharm, Via Giovanni Paolo 2 132, I-84084 Fisciano, SA, Italy
[2] Kazan State Med Univ, Dept Pharmaceut Analyt & Toxicol Chem, Butlerov St 49, Kazan 420012, Russia
[3] Dept Ind Engn, Via Giovanni Paolo 2 132, I-84084 Fisciano, SA, Italy
基金
俄罗斯科学基金会;
关键词
Shell-core microparticles; 5-Fluorouracil; Hydrophilic drug; Ultrasonic atomization; Polyelectrolyte complexation; IN-VITRO; INTERPOLYELECTROLYTE COMPLEXES; DELIVERY-SYSTEMS; SODIUM ALGINATE; MICROPARTICLES; CHITOSAN; RELEASE; 5-FLUOROURACIL; NANOPARTICLES; MICROSPHERES;
D O I
10.1016/j.ijpharm.2016.12.056
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 Eudragite (R) 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. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:50 / 58
页数:9
相关论文
共 31 条
[1]   Naproxen-eudragit® RS100 nanoparticles: Preparation and physicochemical characterization [J].
Adibkia, Khosro ;
Javadzadeh, Yousef ;
Dastmalchi, Siavoush ;
Mohammadi, Ghobad ;
Niri, Fatemeh Kari ;
Alaei-Beirami, Mahmood .
COLLOIDS AND SURFACES B-BIOINTERFACES, 2011, 83 (01) :155-159
[2]   Calcium alginate-carboxymethyl cellulose beads for colon-targeted drug delivery [J].
Agarwal, Tarun ;
Narayana, S. N. Gautham Hari ;
Pal, Kunal ;
Pramanik, Krishna ;
Giri, Supratim ;
Banerjee, Indranil .
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2015, 75 :409-417
[3]   Novel Strategies to Improve the Anticancer Action of 5-Fluorouracil by Using Drug Delivery Systems [J].
Arias, Jose L. .
MOLECULES, 2008, 13 (10) :2340-2369
[4]   5-fluorouracil encapsulated alginate beads for the treatment of breast cancer [J].
Arica, B ;
Çalis, S ;
Kas, HS ;
Sargon, MF ;
Hincal, AA .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2002, 242 (1-2) :267-269
[5]   Development of 5-fluorouracil loaded poly(acrylamide-co-methylmethacrylate) novel core-shell microspheres:: In vitro release studies [J].
Babu, V. Ramesh ;
Sairam, Malladi ;
Hosamani, Kallappa M. ;
Aminabhavi, Tejraj M. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2006, 325 (1-2) :55-62
[6]   Liposoluble vitamin encapsulation in shell-core microparticles produced by ultrasonic atomization and microwave stabilization [J].
Barba, Anna Angela ;
Dalmoro, Annalisa ;
d'Amore, Matteo ;
Lamberti, Gaetano .
LWT-FOOD SCIENCE AND TECHNOLOGY, 2015, 64 (01) :149-156
[7]   Biocompatible nano-micro-particles by solvent evaporation from multiple emulsions technique [J].
Barba, Anna Angela ;
Dalmoro, Annalisa ;
d'Amore, Matteo ;
Vascello, Clara ;
Lamberti, Gaetano .
JOURNAL OF MATERIALS SCIENCE, 2014, 49 (14) :5160-5170
[8]   In vitro dissolution of pH sensitive microparticles for colon-specific drug delivery [J].
Barba, Anna Angela ;
Dalmoro, Annalisa ;
d'Amore, Matteo ;
Lamberti, Gaetano .
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY, 2013, 18 (06) :1399-1406
[9]   Intensification of biopolymeric microparticles production by ultrasonic assisted atomization [J].
Barba, Anna Angela ;
d'Amore, Matteo ;
Cascone, Sara ;
Lamberti, Gaetano ;
Titomanlio, Giuseppe .
CHEMICAL ENGINEERING AND PROCESSING-PROCESS INTENSIFICATION, 2009, 48 (10) :1475-1481
[10]   Microencapsulation effectiveness of small active molecules in biopolymer by ultrasonic atomization technique [J].
Cascone, Sara ;
Lamberti, Gaetano ;
Titomanlio, Giuseppe ;
Barba, Anna Angela ;
d'Amore, Matteo .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 2012, 38 (12) :1486-1493