Department of Chemical Engineering, Curtin University, Sarawak 98009, Malaysia.
Department of Chemical Engineering, University of Tennessee Chattanooga, Tennessee 37403.
J Pharm Sci. 2019 Sep;108(9):2934-2941. doi: 10.1016/j.xphs.2019.03.037. Epub 2019 Apr 16.
Efficient delivery of adequate active ingredients to targeted malignant cells is critical, attributing to recurrent biophysical and biochemical challenges associated with conventional pharmaceutical delivery systems. These challenges include drug leakage, low targeting capability, high systemic cytotoxicity, and poor pharmacokinetics and pharmacodynamics. Targeted delivery system is a promising development to deliver sufficient amounts of drug molecules to target cells in a controlled release pattern mode. Aptameric ligands possess unique affinity targeting capabilities which can be exploited in the design of high pay-load drug formulations to navigate active molecules to the malignant sites. This study focuses on the development of a copolymeric and multifunctional drug-loaded aptamer-conjugated poly(lactide-co-glycolic acid)-polyethylenimine (PLGA-PEI) (DPAP) delivery system, via a layer-by-layer synthesis method, using a water-in-oil-in-water double emulsion approach. The binding characteristics, targeting capability, biophysical properties, encapsulation efficiency, and drug release profile of the DPAP system were investigated under varying conditions of ionic strength, polymer composition and molecular weight (MW), and degree of PEGylation of the synthetic core. Experimental results showed increased drug release rate with increasing buffer ionic strength. DPAP particulate system obtained the highest drug release of 50% at day 9 at 1 M NaCl ionic strength. DPAP formulation, using PLGA 65:35 and PEI MW of ∼800 Da, demonstrated an encapsulation efficiency of 78.93%, and a loading capacity of 0.1605 mg bovine serum albumin per mg PLGA. DPAP (PLGA 65:35, PEI MW∼25 kDa) formulation showed a high release rate with a biphasic release profile. Experimental data depicted a lower targeting power and reduced drug release rate for the PEGylated DPAP formulations. The outcomes from the present study lay the foundation to optimize the performance of DPAP system as an effective synthetic drug carrier for targeted delivery.
高效地将足够的活性成分递送到靶向恶性细胞是至关重要的，这归因于与传统药物递送系统相关的反复出现的生物物理和生化挑战。这些挑战包括药物泄漏、低靶向能力、高全身细胞毒性以及差的药代动力学和药效学。靶向递送系统是一种有前途的发展方向，可以以受控释放模式将足够数量的药物分子递送到靶细胞。适体配体具有独特的靶向亲和力，可以用于设计高载药量的药物制剂，将活性分子导航到恶性部位。本研究专注于开发一种共聚多功能载药适体偶联聚（乳酸-共-乙醇酸）-聚亚乙基亚胺（PLGA-PEI）（DPAP）递药系统，通过层层合成方法，采用油包水双乳液法。研究了 DPAP 系统在不同离子强度、聚合物组成和分子量（MW）以及合成核的聚乙二醇化程度条件下的结合特性、靶向能力、生物物理特性、包封效率和药物释放特性。实验结果表明，随着缓冲离子强度的增加，药物释放速率增加。在 1 M NaCl 离子强度下，DPAP 颗粒系统在第 9 天达到 50%的最高药物释放率。采用 PLGA 65:35 和 MW∼800 Da 的 PEI 的 DPAP 配方，显示出 78.93%的包封效率和 0.1605mg 牛血清白蛋白/每毫克 PLGA 的载药量。DPAP（PLGA 65:35，PEI MW∼25 kDa）配方具有较高的释放速率和两相释放曲线。实验数据表明，PEG 化 DPAP 配方的靶向能力降低，药物释放速率降低。本研究的结果为优化 DPAP 系统作为靶向递送的有效合成药物载体的性能奠定了基础。
