Enhancement of scutellarin oral delivery efficacy by vitamin B12-modified amphiphilic chitosan derivatives to treat type II diabetes induced-retinopathy

Abstract

BackgroundDiabetic retinopathy is the most common complication in diabetic patients relates to high expression of VEGF and microaneurysms. Scutellarin (Scu) turned out to be effective against diabetes related vascular endothelial cell dysfunction. However, its clinical applications have been limited by its low bioavailability. In this study, we formulated and characterized a novel intestinal target nanoparticle carrier based on amphiphilic chitosan derivatives (Chit-DC-VB12) loaded with scutellarin to enhance its bioavailability and then evaluated its therapeutic effect in experimental diabetic retinopathy model.ResultsChit-DC-VB12 nanoparticles showed low toxicity toward the human colon adenocarcinoma (Caco-2) cells and zebra fish within concentration of 250 μg/ml, owing to good biocompatibility of chitosan. The scutellarin-loaded Chit-DC-VB12 nanoparticles (Chit-DC-VB12-Scu) were then prepared by self-assembly in aqueous solution. Scanning electron microscopy and dynamic light scattering analysis indicated that the Chit-DC-VB12-Scu nanoparticles were spherical particles in the sizes ranging from 150 to 250 nm. The Chit-DC-VB12-Scu nanoparticles exhibited high permeation in Caco-2 cell, indicated it could be beneficial to be absorbed in humans. We also found that Chit-DC-VB12 nanoparticles had a high cellular uptake. Bioavailability studies were performed in Sprague–Dawley rats, which present the area under the curve of scutellarin of Chit-DC-VB12-Scu was two to threefolds greater than that of free scutellarin alone. Further to assess the therapeutic efficacy of diabetic retinopathy, we showed Chit-DC-VB12-Scu down-regulated central retinal artery resistivity index and the expression of angiogenesis proteins (VEGF, VEGFR2, and vWF) of retinas in type II diabetic rats.ConclusionsChit-DC-VB12 nanoparticles loaded with scutellarin have better bioavailability and cellular uptake efficiency than Scu, while Chit-DC-VB12-Scu nanoparticles alleviated the structural disorder of intraretinal neovessels in the retina induced by diabetes, and it also inhibited the retinal neovascularization via down-regulated the expression of angiogenesis proteins. In conclusion, the Chit-DC-VB12 nanoparticles enhanced scutellarin oral delivery efficacy and exhibited potential as small intestinal target promising nano-carriers for treatment of type II diabetes induced-retinopathy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-017-0251-z) contains supplementary material, which is available to authorized users.

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

“…Scutellarin-loaded bovine serum albumin nanoparticles have been found to enhance bioavailability and to achieve sustained release profile of scutellarin following parenteral administration [267]. Scutellarin-loaded amphiphilic chitosan derivatives nanoparticles were found to enhance oral bioavailability (roughly two-to three-fold), elimination half-life, and cellular uptake of scutellarin than free scutellarin [268]. In addition, the nanoformulation could attenuate diabetic retinopathy via suppressing VEGF, VEGF receptor 2 (VEGFR2), and von Willebrand factor (vWF) expressions without affecting hyperglycaemia [268].…”

“…Scutellarin-loaded amphiphilic chitosan derivatives nanoparticles were found to enhance oral bioavailability (roughly two-to three-fold), elimination half-life, and cellular uptake of scutellarin than free scutellarin [268]. In addition, the nanoformulation could attenuate diabetic retinopathy via suppressing VEGF, VEGF receptor 2 (VEGFR2), and von Willebrand factor (vWF) expressions without affecting hyperglycaemia [268]. However, more research is required to optimize a suitable nanoformulation for the oral delivery of scutellarin.…”

“…In this regard, the PLA/PGA ratio in PLGA is a critical factor and the effects of different grades of PLGA as nanocarriers need to be specifically addressed. Chitosan has been regarded as a suitable nanocarrier for the oral delivery of curcumin, naringenin, quercetin, gymnemic acid, rosmarinic acid, scutellarin, silybin, and others, which improves compliance and pharmacokinetic attributes of the aforementioned antidiabetic phytochemicals [200,220,224,240,247,268]. Pluronic has also been found to be another suitable nanocarrier in developing curcumin, apigenin, baicalin, stevioside, silymarin, silybin, and thymoquinone nanoformulations [121,138,148,196,232,269,295,297].…”

Synergistic inhibition of metastatic breast cancer by dual-chemotherapy with excipient-free rhein/DOX nanodispersions

“…The intensive clinical trials and final FDA approvals should be needed for these materials as excipients. Moreover, production of nanomedicines is often too complicated to develop scaling up manufacturing processes [21,22]. Therefore, it is necessary to design a "green" approach to design nanomedicines without "toxic" excipients.…”

Synthesis of chitosan-iron keplerate composite as an adsorbent for removal of toxic ions from water

“…Due to these advantages, chitosan and its derivatives (Schiff bases, grafted copolymers, composites, nanoparticles, etc.) have many applications in drug release [8][9][10][11][12][13][14][15][16][17] (for more details regarding the application of chitosan and its derivatives in drug release, see review, [18] and references therein), biological activity [19][20][21][22][23][24] (for more details regarding the biological activity of chitosan and its derivatives, see review, [25] and references therein)), beverages and food industry [26][27][28][29] (also see [30] and references therein, an extensive review reporting the application of chitosan and its derivatives in beverages and food industry) as well as membranes for the removal of various pollutants such as metals, ions, dyes, pharmaceuticals/drugs, phenols, pesticides, herbicides, etc. [31][32][33][34][35][36][37][38][39][40][41][42][43][44] (references [31] and [44] are extensive reviews).…”