Dubashynskaya Natallia V, Petrova Valentina A, Romanov Dmitry P, Skorik Yury A
Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoy pr. V.O. 31, 199004 St. Petersburg, Russia.
Institute of Silicate Chemistry of the Russian Academy of Sciences, Adm. Makarova emb. 2, 199034 St. Petersburg, Russia.
Materials (Basel). 2022 Aug 25;15(17):5860. doi: 10.3390/ma15175860.
Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. The MET-CNW-ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of -43 mV. In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. The introduction of CNWs into the MET-ALG system not only prolonged the drug release, but also increased the mucoadhesive properties by about 1.3 times. Thus, novel CNW-ALG hydrogels are promising carriers for pH sensitive drug delivery carriers.
基于部分脱乙酰化几丁质纳米晶须(CNW)和阴离子多糖的聚电解质复合物(PEC),其特性(粒径、ζ电位和pH敏感性)会因制备条件而变化,从而能够开发出具有活性药物持续释放特性的聚合物纳米平台。本研究聚焦于基于CNW与海藻酸钠(ALG)的PEC开发水凝胶,用于潜在的阴道给药,该水凝胶在酸性阴道环境中能实现pH依赖的抗生素可控释放,并且由于药物的持续释放特性以及多糖的粘膜粘附特性而具有延长的药理作用。所需的水凝胶是通过CNW与ALG之间的静电相互作用(形成PEC)、随后ALG链的分子缠结以及额外氢键的形成而形成的。在pH 5.5且CNW:ALG比例为1:2的条件下获得了具有所需特性的甲硝唑(MET)递送系统。水凝胶组合物中的MET-CNW-ALG微粒的表观流体动力学直径约为1.7 µm,ζ电位为-43 mV。体外释放研究表明,从设计的水凝胶中药物具有延长的pH敏感释放特性;在pH 7.4和pH 4.5条件下,分别有37%和67%的MET在24小时内释放。将CNW引入MET-ALG系统不仅延长了药物释放,还使粘膜粘附特性提高了约1.3倍。因此,新型CNW-ALG水凝胶是有前景的pH敏感药物递送载体。