Liposomes containing cyclodextrins or meglumine to solubilize and improve the bioavailability of poorly soluble drugs
Liposomes containing cyclodextrins or meglumine to solubilize and improve the bioavailability of poorly soluble drugs
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DOI：
10.1016/j.molliq.2016.12.035
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发表时间：
2017-03-01
影响因子：
6
通讯作者：
Longhi, Marcela R.
中科院分区：
文献类型：
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作者：
Aloisio, Carolina;Antimisiaris, Sophia G.;Longhi, Marcela R.
众所周知，难溶性载药脂质体具有溶解和改善所携带分子的生物利用度的能力，并且可以提供作为口服药物递送系统的益处。本研究旨在评价β-环糊精（β CD）、甲基-β CD（M β CD）、羟丙基-β CD（HP β CD）和葡甲胺（MEG）对难溶性药物磺胺甲基嘧啶（SMR）和吲哚美辛（INM）的口服给药作用。分别采用薄膜水合法和脱水-再水合法制备了含卵磷脂（PC）和胆固醇（CHO）的脂质体，并将SMR或INM以普通药物或包合物的形式掺入脂质体中。通过粒度、多分散性和zeta电位测量对系统进行表征，并通过H-1 NMR进行药物-组分相互作用研究。脂质体在SMR、INM、CD和MEG存在下的稳定性通过囊泡包封的钙黄绿素在37 ℃下在pH7.4的溶液中孵育长达48小时后的保留来测定。药物包封，以及药物释放，估计所有类型的脂质体制备。1H NMR研究表明，药物与脂质体的脂质发生相互作用，表明药物在脂质双层中的位置。脂质体在药物pCD、HP 13 CD或MEG存在下表现出高稳定性。当使用MEG和HP β CD时，具有PC：CHO 3：1脂质体的SMR和INM分别实现了最高包封值（5636.28和439.54 mmol/ mol），这意味着与无配体制剂相比，实现了18倍和43倍的SMR和INM掺入。体外释放研究表明，配体对脂质体中药物的释放有很强的影响。© 2016 Elsevier B. V.版权所有。
Poorly soluble drug-loaded liposomes are well known for their ability to solubilize and improve the bioavailability of the carried molecules, and may provide benefits as oral drug delivery systems. In this work, we aim to evaluate the effect of the incorporation of beta-cyclodextrin (beta CD), methyl-beta CD (M beta CD), hydroxypropil-beta CD (HP beta CD) and meglumine (MEG) in liposomes for the oral delivery of the poorly water-soluble drugs, sulfamerazine (SMR) and indomethacin (INM). Liposomes with egg phosphatidylcholine (PC) and cholesterol (CHO), incorporating SMR or INM as plain drug or inclusion complexes, were prepared using the thin film hydration method or dehydration-rehydration method, respectively. The systems were characterized by particle size, polydispersity and zeta potential measurements, and drug -component interaction studies were performed by H-1 NMR. Liposome stability in presence of SMR, INM, CD and MEG was determined by,the retention of vesicle encapsulated calcein after incubation in solutions of pH 7.4, at 37 C for up to 48 h. Drug entrapment, as well as drug release, were estimated for all liposome types prepared. The 1H NMR studies revealed that the drugs presented interaction with lipids of the liposomes, suggesting the location of the drugs in the lipid bilayer. The liposomes presented high stability in the presence of the drugs, pCD, HP13CD or MEG. The highest entrapment values were achieved for SMR and INM with PC:CHO 3:1 liposomes when MEG and HPpCD were used, respectively (5636.28 and 439.54 mmol/ mol), meaning that 18 and 43 times higher incorporation of SMR and INM were achieved in comparison with the ligand-free formulation. The in-vitro release studies showed a strong influence of the ligands on the delivery of the drugs from the liposomes. 2016 Elsevier B.V. All rights reserved.