Surfactant-Free Chitosan/Cellulose Acetate Phthalate Nanoparticles: An Attempt to Solve the Needs of Captopril Administration in Paediatrics

Abstract

The Paediatric Committee of the European Medicines Agency encourages research into medicinal products for children, in particular, the development of an age-appropriate formulation of captopril is required in the cardiovascular therapeutic area. The aim of this study was the development of a liquid formulation using nanoparticles based only on chitosan and cellulose acetate phthalate containing captopril for the treatment of hypertension, heart failure and diabetic nephropathy in paediatric patients. Nanoparticles were prepared by a nanoprecipitation method/dropping technique without using surfactants, whose use can be associated with toxicity. A range of different cellulose to chitosan weight ratios were tested. A good encapsulation efficiency (61.0 ± 6.5%) was obtained when a high chitosan concentration was used (1:3 ratio); these nanoparticles (named NP-C) were spherical with a mean diameter of 427.1 ± 32.7 nm, 0.17 ± 0.09 PDI and +53.30 ± 0.95 mV zeta potential. NP-C dispersion remained stable for 28 days in terms of size and drug content and no captopril degradation was observed. NP-C dispersion released 70% of captopril after 2 h in pH 7.4 phosphate buffer and NP-C dispersion did not have a cytotoxicity effect on neonatal human fibroblasts except at the highest dose tested after 48 h. As a result, chitosan/cellulose nanoparticles could be considered a suitable platform for captopril delivery in paediatrics for preparing solid/liquid dosage forms.

Controlled release of doxorubicin from gelatin-based nanoparticles: theoretical and experimental approach

“…Other sharp peaks at 3348 cm −1 and 2927 cm −1 of gelatin are related to the N–H stretching of the amide group and asymmetric stretching of the C–H group, respectively. 35,36…”

“…Other sharp peaks at 3348 cm À1 and 2927 cm À1 of gelatin are related to the N-H stretching of the amide group and asymmetric stretching of the C-H group, respectively. 35,36 All these peaks can be seen in the Ge-NPs-5 and Ge-NPs-10 spectra. In the amide-I and amide-II regions, there was a minor shift.…”

Hydrogel Bioinks of Alginate and Curcumin-Loaded Cellulose Ester-Based Particles for the Biofabrication of Drug-Releasing Living Tissue Analogs

“…Similarly, CEpCUR particles also revealed no significant cytotoxic effect in the tested concentrations, with cell viabilities of 96.7 ± 8.4% (CEpCUR_1%), 88.9 ± 3.8% (CEpCUR_5%), and 83.3% ± 3.4% (CEpCUR_10%) after 24 h. Since all of the cell viability values obtained are well above the threshold of 70%, both particles (with and without curcumin) are considered noncytotoxic toward HaCaT cells in the investigated concentrations, as defined by the ISO 10993-5:2009, thus confirming their potential for biological applications like 3D bioprinting. 58 Furthermore, the results are consonant with studies with other particles available in the literature, namely the works of Varshosaz et al, 59 using cellulose acetate butyrate particles loaded with nevirapine for HIV treatment (reporting viabilities above 80% against J774A1 cells), and of Gonzaĺez et al 60 concerning the use of cellulose acetate phthalate/chitosan particles for the administration of captopril using HFF-1 cells.…”

Development of Medicines for Rare Pediatric Diseases

“…It is worth mentioning that when developing pediatric medicines, the formulator should bear in mind that the number of ingredients must be as low as possible to avoid potentially toxic or unsuitable excipients for children. To comply with safety requirements, the authors did not use surfactants to stabilize the colloidal dispersion [4][5][6]. Nieto González et al developed nanoparticles based on chitosan and cellulose acetate phthalate containing captopril (a hydrophilic drug) for the treatment of hypertension, heart failure and diabetic nephropathy in pediatric patients [4].…”

“…To comply with safety requirements, the authors did not use surfactants to stabilize the colloidal dispersion [4][5][6]. Nieto González et al developed nanoparticles based on chitosan and cellulose acetate phthalate containing captopril (a hydrophilic drug) for the treatment of hypertension, heart failure and diabetic nephropathy in pediatric patients [4]. Nanoprecipitation is mainly employed for the encapsulation and solubilization of hydrophobic drugs, thus Zuccari et al first prepared nanoparticles made of a water-soluble cationic copolymer (P5) obtained by copolymerizing the laboratorymade monomer 4-ammoniumbuthylstyrene hydrochloride with di-methyl-acrylamide as an uncharged diluent, and loaded with fenretinide, a lipophilic retinoid, known to be active against neuroblastoma [5].…”