Development and in vivo evaluation of self‐microemulsion as delivery system for α‐mangostin

Abstract

α-Mangostin (MG) is a versatile bioactive compound isolated from mangosteen and possesses significant pharmacokinetic shortages. To augment the potential clinical efficacy, MG-loaded self-microemulsion (MG-SME) was designed and prepared in this study, and its potential as a drug loading system was evaluated based on the pharmacokinetic performance and tissue distribution feature. The formula of MG-SME was optimized by an orthogonal test under the guidance of ternary phase diagram, and the prepared MG-SME was characterized by encapsulation efficiency, size distribution, and morphology. Optimized high performance liquid chromatography method was employed to determine concentrations of MG and characterize the pharmacokinetic and tissue distribution features of MG in rodents. It was found that diluted MG-SME was characterized as spherical particles with a mean diameter of 24.6 nm and an encapsulation efficiency of 87.26%. The delivery system enhanced the area under the curve of MG by 4.75 times and increased the distribution in lymphatic organs. These findings suggested that SME as a nano-sized delivery system efficiently promoted the digestive tract absorption of MG and modified its distribution in tissues. The targeting feature and high oral bioavailability of MG-SME promised a good clinical efficacy, especially for immune diseases.

<p>Nanoparticle Drug Delivery Systems for α-Mangostin</p>

“…The nanomicelle uptake was mediated by endocytosis, a finding that indicated intracellular delivery of α-mangostin that could be associated with potential cytotoxicity (IC 50 of 8.9 ± 0.2 μg/mL). 82 Chitosan, PLGA Colloidal extraction solvent evaporation [75] PEG, PLA Emulsion/solvent evaporation techniques [76] PLGA Double emulsion solvent evaporation method [42] EC-MC Spray drying [77] Chitosan, alginate and genipin Ionotropic gelation method [78] β-cyclodextrin Inclusion complex technique [79] β-cyclodextrin-chitosan Inclusion complex [80] β-cyclodextrin Inclusion complex [81] Nanomicelles PVP Solvent evaporation method [82] MPEG and PLA Single-step self-assembly method [83] MPEG and PCL Self-assembly method [84] Liposome nanoparticles Transferrin Thin film hydration [85] Soya lecithin Phase separation coacervation method [86] Cholesterol, Tween 60 and ethanol Film hydration method [87] Solid lipid nanoparticles Lavender essential oil and cetyl palmitate Hot and high-pressure homogenisation techniques [88] PLGA and CD44 thioaptamer Nanoprecipitation combined with self-assembly [89] Nanofibres Thiolated chitosan Electrospinning [90] PVP Electrospinning [91] Metal nanoparticles Ag (silver) Chemical reaction by using silver nitrate (AgNO3) [92] Gold, PEI, cyclodextrin and tanshinone Chemical reaction using polyethyleneimine (PEI) [93] Emulsion nanoparticle Captex 200 P, Tween 80, carbopol 90 and silica Solid self-emulsification [94] Oleic acid, isopropyl myristate, Cremophor EL, Tween 80, carboxymethylcellulose sodium Self-microemulsion [31] In another study, α-mangostin nanomicelles with methoxypoly(ethylene glycol)-poly(lactide) (MPEG-PLA) were developed by a single-step self-assembly method for malignant glioma. In vitro and in vivo assays showed that the α-mangostin/MPEG-PLA nanoparticles inhibited cell growth and induced apoptosis-with cleaved caspase expression, DNA fragmentation, downregulation of antiapoptotic molecules and up-regulation of apoptotic molecules.…”

“…The targeted system and high oral bioavailability of α-mangostin with self-microemulsion provides excellent performance for clinical drug efficacy. 31…”

“…Several types of nanoparticles have been formulated for the α-mangostin compound, including nanolipids, nanopolymerics, nanomicelles, nanoliposomes, nanofibers and metal nanoparticles. 19,20,[30][31][32][33][34] The results are substantial, with significantly improved solubility for α-mangostin. Therefore, controlled and targeted drug delivery systems can be created by modified nanoparticle technology.…”

Mangosteen Pericarp and Its Bioactive Xanthones: Potential Therapeutic Value in Alzheimer’s Disease, Parkinson’s Disease, and Depression with Pharmacokinetic and Safety Profiles

“…α-MG was universally distributed into almost all organs, including the liver, kidney, and brain. This study demonstrated that the microemulsion was an efficient delivery system for α-MG to cross BBB [ 115 ]. Another proposed delivery system was transferrin-modified liposomes (Tf(α-MG) liposome) administered through i.v.…”

“…and i.v. administrations may not be appropriate to apply to the actual treatment regimen of AD in humans [ 115 ]. Oral administrations of α-MG may possess limitations due to its hydrophobic nature, poor aqueous solubility and stability, low bioavailability, and lack of accumulation in the target organs including brain [ 116 , 117 ].…”