Yue Isaac C, Poff Jason, Cortés María E, Sinisterra Ruben D, Faris Caroline B, Hildgen Patrice, Langer Robert, Shastri V Prasad
Harvard School of Dental Medicine, Boston, MA, USA.
Biomaterials. 2004 Aug;25(17):3743-50. doi: 10.1016/j.biomaterials.2003.09.113.
An implantable, anti-microbial delivery device for the treatment of periodontal disease has been developed. In this polymer-based delivery system, the encapsulation efficiency, release characteristics, and bioactivity of anti-microbial agent were controlled by the complexation of the drug with cyclodextrins of differing lipophilicity. Microparticles of poly(dl-lactic-co-glycolic acid) (PLGA) containing chlorhexidine (Chx) free base, chlorhexidine digluconate (Chx-Dg) and their association or inclusion complex with methylated-beta-cyclodextrin (MBCD) and hydroxypropyl-beta-cyclodextrin (HPBCD) were prepared by single emulsion, solvent evaporation technique. It was observed that encapsulation efficiency and release of the chlorhexidine derivatives from the microparticles was a function of the lipophilicity of the cyclodextrin. Complexation of the poorly water soluble Chx with the more hydrophilic HPBCD resulted in 62% higher encapsulation efficiency and longer duration of sustained release over a 2-week period than complexation with the more lipophilic MBCD. In contrast, the complexation of the more water-soluble derivative of chlorhexidine, Chx-Dg, with the more lipophilic MBCD improved encapsulation efficiency by 12% and prolonged its release in comparison to both the free Chx-Dg and its complex with HPBCD. Furthermore, it was observed that the initial burst effect could be diminished by complexation with CD. Preliminary studies have shown that the chlorhexidine released from PLGA chips is biologically active against bacterial population that is relevant in periodontitis (P. gingivalis and B. forsythus) and a healthy inhibition zone is maintained in agar plate assay over a period of at least a 1-week. The PLGA/CD delivery system described in this paper may prove useful for the localized delivery of chlorhexidine salts and other anti-microbial agents in the treatment of periodontal disease where prolonged-controlled delivery is desired.
一种用于治疗牙周疾病的可植入抗菌递送装置已被研发出来。在这种基于聚合物的递送系统中，抗菌剂的包封效率、释放特性和生物活性通过药物与不同亲脂性环糊精的络合作用来控制。采用单乳液溶剂蒸发技术制备了含有氯己定（Chx）游离碱、葡萄糖酸氯己定（Chx-Dg）及其与甲基化β-环糊精（MBCD）和羟丙基-β-环糊精（HPBCD）的缔合或包合络合物的聚（dl-乳酸-共-乙醇酸）（PLGA）微粒。观察到氯己定衍生物从微粒中的包封效率和释放是环糊精亲脂性的函数。水溶性较差的Chx与亲水性更强的HPBCD络合，与亲脂性更强的MBCD络合相比，包封效率提高了62%，并在2周内实现了更长时间的持续释放。相比之下，氯己定的水溶性更强的衍生物Chx-Dg与亲脂性更强的MBCD络合，与游离的Chx-Dg及其与HPBCD的络合物相比，包封效率提高了12%，并延长了其释放时间。此外，观察到与环糊精络合可减少初始突释效应。初步研究表明，从PLGA芯片释放的氯己定对与牙周炎相关的细菌群体（牙龈卟啉单胞菌和福赛坦氏菌）具有生物活性，并且在琼脂平板试验中至少1周的时间内保持健康的抑菌圈。本文所述的PLGA/CD递送系统可能被证明对在需要长期控制递送的牙周疾病治疗中局部递送氯己定盐和其他抗菌剂有用。
