Octenyl-succinylated inulin for the encapsulation and release of hydrophobic compounds

Abstract

Octenyl-succinylated inulins (OSA-inulin) were synthesized in aqueous solutions using inulin with varying degrees of polymerization (DP). They were characterized using 1 H NMR and FTIR and their degrees of substitution were determined. All the samples formed micellar aggregates in aqueous solution above a critical aggregation concentration (CAC) and solubilized beta-carotene. The amount of beta carotene solubilized within the micelles ranged from 12 -25mg/g of OSA-inulin and depended on the inulin molar mass. Dynamic light scattering showed that the aggregates, with and without dissolved beta-carotene, were ~10-15 nm in size and this was confirmed by Transmission Electron Microscopy which also indicated that the micelles had a globular shape. OSA-inulin particles containing encapsulated beta-carotene were produced by freeze-drying. The encapsulated beta-carotene was not released from the freeze-dried particles when introduced into simulated gastric fluid at pH 2.5 but was readily released in simulated small intestinal fluid at pH 7. The results demonstrate the potential application of OSA-inulin in the encapsulation, dissolution and targeted delivery of hydrophobic drug molecules for nutraceutical, pharmaceutical and medical applications.

Potential applications of hydrophobically modified inulin as an active ingredient in functional foods and drugs - A review

“… Walz, Hagemann et al (2018) AcIn inulin. Mesalamine Spray-drying 109 % ± 10 % and 84 % ± 5 % Mesalamine was encapsulated with high encapsulation efficiency along with high enzymatic degradability Walz, Hagemann et al (2018) Lauryl carbamate derivative of inulin (Inutec SP1®, INT) PTX and Doxorubicin Thin-film hydration for INT-Micelles 76.6 ± 11.23 % for INT-P, 89.5 ± 4.6 % for INT-D, 89.9 ± 3 % for INT-DP for DOX, and 48.6 ± 0.8 % for PTX The efficiency of drug encapsulation is very high for INT micelles with a clathrin-mediated endocytosis pathway Kesharwani et al (2019) OSA-inulin Beta-carotene Freeze-drying N/A Beta-carotene was solubilized within the micelles ranging from 12 −25 mg/g of OSA-inulin Han et al (2020) Lauryl carbamate derivative of inulin (Inutec SP1®, INT) PTX Thin film hydration and solvent evaporation for INT-micelles 95.66 ± 2.25 % PTX-loaded INT micelles demonstrated outstanding drug encapsulation efficiency and drug loading with in vivo antitumor activity Muley et al (2016) INVITE CUR and CLX dialysis method for INVITE micelles 37.1 ± 1.5 for INVITE-CUR and 52.3 ± 1.3 for INVITE-CLX Encapsulation of CUR and CLX in INVITE micelles boosted the water solubility of CUR and CLX and Encapsulation efficiency of INVITE-CLX was higher than that of INVITE-CUR Mandracchia et al (2016) RGD-peptide conjugated inulin EPB Modified nanoprecipitation and dialysis for inulin-ibuprofen conjugates 81.3 % The RGD-conjugated EPB-loaded nanoparticles exhibit excellent encapsulation efficiency and antitumor efficacy Zhang et al (2016) OSA = octenyl succinic anhydrides, DDSA = dodecenyl su...…”

“… Han et al (2020) investigated how changes in pH trigger drug release, applying octenyl-succinylated inulin for the encapsulation and release of hydrophobic compounds. OSA-inulin particles were fabricated with beta-carotene by freeze-drying.…”

“…In the recent few decades, an upsurge in the global frequency of colonic diseases has resulted in the increased urgency for operational local treatment of colonic diseases, for instance, Crohn’s disease, ulcerative colitis, amebiasis, colonic cancer, colorectal cancer (CRC), inflammatory bowel disease (IBD), etc., for more effective and safer drug therapies. There is an extreme need for targeted drug delivery into the colon for local treatment of a range of bowel diseases and colonic pathologies through the systemic delivery of protein and peptide drugs (Walz et al, 2017, Han et al, 2020 ; Philip & Philip, 2010 ).…”

“…When administered into gastric fluid at pH 2.5, the encapsulated beta-carotene was not released from the freeze-dried particles. Conversely, it was readily released in small intestinal fluid at pH 7 ( Han et al, 2020 ). The ability of mesenchymal stromal cells (MSCs), when administered intravenously, to discharge a massive amount of bioactive molecules with immunomodulatory properties makes them a great drug repository that can travel especially to damaged tissues; this capability has been utilized by Tripodo, Chlapanidas et al (2015) to design a drug delivery system based on MSCs loaded with curcumin-INVITE (inulin- d -α-tocopherol succinate bioconjugates) micelles for the treatment of neurodegenerative diseases.…”

“…It was revealed that these types of inulin derivatives adsorbed at the liquid-liquid interface, solid-liquid interface, and air-water interface and produced micellar-like structures in the solution above a critical concentration. Moreover, the HMI derivatives contributed excellent encapsulation efficiency, reaching up to 100 %, and near-spherical drug-loaded micellar aggregates of ∼250 nm, resulting in prolonged drug and vaccine release ( Han et al, 2020 ; Kesharwani, Dachineni, Bhat, & Tummala, 2019 ; Walz, Hagemann, Trentzsch, Weber, & Henle, 2018 ). The commercially available Inutec®SP1 has been widely used for the targeted release of anticancer drugs, particularly paclitaxel ( Muley, Kumar, El Kourati, Kesharwani, & Tummala, 2016 ).…”