Synthesis, Characterization, and Drug Delivery Application of Self-assembling Amphiphilic Cyclodextrin
- PDF / 2,619,915 Bytes
- 16 Pages / 595.276 x 790.866 pts Page_size
- 35 Downloads / 169 Views
Research Article Synthesis, Characterization, and Drug Delivery Application of Self-assembling Amphiphilic Cyclodextrin Mayank R. Patel,1 Dimitrios A. Lamprou,2,3 and Pradeep R. Vavia1,4
Received 23 July 2019; accepted 10 October 2019 Abstract. The main aim of the research was to synthesize amphiphilic cyclodextrin (AMCD) by substituting C12 alkyl chain to a β-cyclodextrin (βCD) in a single step and to study its self-assembly in an aqueous medium. The drug delivery application of the AMCD was also evaluated by encapsulating tamoxifen citrate as a model hydrophobic drug. AMCD was able to self-assemble in aqueous media, forming nanovesicles of size < 200 nm, capable of encapsulating tamoxifen citrate (TMX). Molecular docking and MD simulation studies revealed the interaction between TMX and AMCD which formed a stable complex. TEM and AFM studies showed that nanovesicles were perfectly spherical having a smooth surface and a theoretical AMCD bilayer thickness of ~ 7.2 nm as observed from SANS studies. XRD
Electronic supplementary material The online version of this article (https://doi.org/10.1208/s12249-019-1572-z) contains supplementary material, which is available to authorized users. 1
Center for Novel Drug Delivery Systems, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, University Under Section 3 of UGC Act – 1956, Elite Status and Centre of Excellence – Govt. of Maharashtra, TEQIP Phase III Funded, Matunga (E), Mumbai, 400019, India. 2 Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK. 3 School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK. 4 To whom correspondence should be addressed. (e–mail: [email protected]) Abbreviations: 13C NMR, carbon-13 nuclear magnetic resonance; 1H NMR, proton nuclear magnetic resonance; AFM , atomic force microscopy; AMCD, amphiphilic cyclodextrin; ATCC, American type culture collection; CD, Cyclodextrin; CO2, carbon dioxide; DCM, dichloromethane; DLS, dynamic light scattering; DMEM, Dulbecco’s modified Eagle medium; DMF, N,N-dimethylformamide; DMSO, dimethyl sulfoxide; DMSO-D 6 , deuterated dimethyl sulfoxide; Ds, degree of substitution; DSC, differential scanning calorimetry; FBS, fetal bovine serum; FNV, fluorescein-loaded AMCD nanovesicles; FTIR, Fourier-transform infrared spectroscopy; HPLC, high-performance liquid chromatography; HSQC, heteronuclear single quantum correlation; IC 50 , half maximal inhibitory concentration; IV, intravenous; KBr, potassium bromide; LD50, median lethal dose; MALDI-TOF, matrix-assisted laser desorption/ionization-time-of-flight; MTT, [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]; MβCD, methyl beta cyclodextrin; PBS, phosphate buffer saline; PES, polyether sulfone; PLGA, poly(lactic-co-glycolic acid); PM, physical mixture; R.T., room temperature; RBC, red blood cells; SANS, smallangle neutron scattering; SMEDDS, self-micro emulsifying drug delivery system; TEA, trieth
Data Loading...
