Chesneau Cléa, Sow Alpha Oumar, Hamachi Fadila, Michely Laurent, Hamadi Séna, Pires Rémy, Pawlak André, Belbekhouche Sabrina
Université Paris Est Creteil, CNRS, Institut Chimie et Matériaux Paris Est, UMR 7182, 2 Rue Henri Dunant, F-94320 Thiais, France.
Université Paris Est, Faculté de Médecine, UMRS 955, Créteil, F-94010 France, UMRS 955, F-94010 Créteil, France.
Pharmaceutics. 2023 Feb 15;15(2):653. doi: 10.3390/pharmaceutics15020653.
Tailor-made and designed micro- and nanocarriers can bring significant benefits over their traditional macroscopic counterparts in drug delivery applications. For the successful loading and subsequent release of bioactive compounds, carriers should present a high loading capacity, trigger release mechanisms, biodegradability and biocompatibility. Hydrophobic drug molecules can accumulate in fat tissues, resulting in drawbacks for the patient's recovery. To address these issues, we propose to combine the advantageous features of both host molecules (cyclodextrin) and calcium carbonate (CaCO) particles in order to load hydrophobic chemicals. Herein, hybrid cyclodextrin-CaCO micro- to nano-particles have been fabricated by combining NaCO solution and CaCl solution in the presence of an additive, namely poly (vinylsulfonic acid) (PVSA) or glycerol (gly). By investigating experimental parameters and keeping the NaCO and CaCl concentrations constant (0.33 M), we have evidenced that the PVSA or gly concentration and mixing time have a direct impact on the final cyclodextrine-CaCO particle size. Indeed, by increasing the concentration of PVSA (5 mM to 30 mM) or gly (0.7 mM to 4 mM) or the reaction time (from 10 min to 4 h), particles with a size of 200 nm could be reached. Interestingly, the vaterite or calcite form could also be selected, according to the experimental conditions. We hypothesised that the incorporation of PVSA or gly into the precipitation reaction might reduce the nucleation rate by sequestering Ca. The obtained particles have been found to keep their crystal structure and surface charge after storage in aqueous media for at least 6 months. In the context of improving the therapeutic benefit of hydrophobic drugs, the developed particles were used to load the hydrophobic drug tocopherol acetate. The resulting particles are biocompatible and highly stable in a physiological environment (pH 7.4, 0.15 M NaCl). A selective release of the cargo is observed in acidic media (pH lower than 5).
定制设计的微米和纳米载体在药物递送应用中比传统的宏观载体具有显著优势。为了成功负载并随后释放生物活性化合物，载体应具有高负载能力、触发释放机制、生物可降解性和生物相容性。疏水性药物分子会在脂肪组织中蓄积，给患者康复带来不利影响。为解决这些问题，我们提议将主体分子（环糊精）和碳酸钙（CaCO₃）颗粒的优势特性结合起来，以负载疏水性化学物质。在此，通过在添加剂（即聚（乙烯磺酸）（PVSA）或甘油（gly））存在的情况下将Na₂CO₃溶液和CaCl₂溶液混合，制备了环糊精 - CaCO₃杂化微米至纳米颗粒。通过研究实验参数并保持Na₂CO₃和CaCl₂浓度恒定（0.33 M），我们证明PVSA或gly的浓度以及混合时间对最终环糊精 - CaCO₃颗粒大小有直接影响。实际上，通过增加PVSA（5 mM至30 mM）或gly（0.7 mM至4 mM）的浓度或反应时间（从10分钟至4小时），可以得到尺寸为200 nm的颗粒。有趣的是，根据实验条件还可以选择球霰石或方解石形式。我们推测将PVSA或gly引入沉淀反应可能通过螯合Ca²⁺降低成核速率。已发现所得颗粒在水性介质中储存至少6个月后仍保持其晶体结构和表面电荷。在提高疏水性药物治疗效果的背景下，所制备的颗粒用于负载疏水性药物醋酸生育酚。所得颗粒具有生物相容性，并且在生理环境（pH 7.4，0.15 M NaCl）中高度稳定。在酸性介质（pH低于5）中观察到货物的选择性释放。
