Development of Octreotide-Loaded Chitosan and Heparin Nanoparticles: Evaluation of Surface Modification Effect on Physicochemical Properties and Macrophage Uptake

Mahdieh Ghofrani; Leila Rezaie Shirmard; Pouya Dehghankelishadi; Mohsen Amini; Farid A Dorkoosh

doi:10.1016/j.xphs.2019.05.002

Development of Octreotide-Loaded Chitosan and Heparin Nanoparticles: Evaluation of Surface Modification Effect on Physicochemical Properties and Macrophage Uptake

J Pharm Sci. 2019 Sep;108(9):3036-3045. doi: 10.1016/j.xphs.2019.05.002. Epub 2019 May 10.

Authors

Mahdieh Ghofrani¹, Leila Rezaie Shirmard², Pouya Dehghankelishadi¹, Mohsen Amini³, Farid A Dorkoosh⁴

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-645, Tehran, Iran.
² Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
³ Department of Medicinal Chemistry, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-645, Tehran, Iran. Electronic address: Dorkoosh@tums.ac.ir.

PMID: 31082402
DOI: 10.1016/j.xphs.2019.05.002

Abstract

Octreotide (OCT) is a therapeutic peptide which is administered for the treatment of acromegaly. The purpose of this study was to design a new polyethylene glycol (PEG)-conjugated nanoparticle (PEG-NP) to overcome the short half-life and poor stability of OCT. The developed PEG-NPs were compared with non-PEGylated NPs with respect to their size, morphological characteristics, loading efficiency, release profile, and macrophage uptake. The OCT-loaded NPs and PEG-NPs were prepared by ionic complexion of chitosan (Cs) with either heparin (Hp) or PEGylated heparin (PEG-Hp). The chemical structure of PEG-Hp was confirmed by IR and proton nuclear magnetic resonance. Morphological analyses by scanning electron microscopy showed that NPs and PEG-NPs have a uniform shape. Dynamic laser scattering measurements indicated that hydrodynamic diameter of NPs and PEG-NPs were 222.5 ± 10.0 nm and 334.9 ± 6.7 nm, respectively. NPs and PEG-NPs had a positive zeta potential of about 32.5 ± 1.1 mv and 20.6 ± 2.4 mv, respectively. Entrapment efficiency was 61.4 ± 1.0% and 55.7 ± 2.4% for NPs and PEG-NPs, respectively. Compared with the NPs, the PEG-NPs exhibited a slower release profile. Subsequently, fluorescein isothiocyanate-labeled chitosanCs was synthesized and used to evaluate the stealth characteristic of PEG-NPs. In vitro macrophage uptake of fluorescently labeled NPs was measured by flow cytometry.

Keywords: chitosan; drug delivery system(s); heparin; peptide delivery; polyethylene glycol.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acromegaly / drug therapy
Animals
Cells, Cultured
Chitosan / chemistry
Drug Carriers / chemistry*
Drug Stability
Half-Life
Heparin / chemistry
Humans
Macrophages, Peritoneal / metabolism*
Mice
Nanoparticles / chemistry
Octreotide / administration & dosage
Octreotide / pharmacokinetics*
Particle Size
Polyethylene Glycols / chemistry
Primary Cell Culture

Substances

Drug Carriers
Polyethylene Glycols
Heparin
Chitosan
Octreotide