Tuning the Emulsion Properties Influences the Size of Poly(Caprolactone) Particles for Drug Delivery Applications.

IF 5 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Ashbey N Manning, Claire E Rowlands, Hope Saindon, Brittany E Givens
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Abstract

Advances in drug delivery have been accelerated with the addition of polymeric drug carriers. Direct delivery to a target site is a promising step in developing effective drug and gene therapies to treat disease. The efficacy of these drug carriers heavily relies on cell uptake without compromising critical cellular processes that promote cell viability. Drug release from biodegradable polymers is mediated largely by polymer degradation, and therefore the rate of polymer degradation dictates the feasibility of drug delivery applications. Traditionally, poly(caprolactone) (PCL) has only been used in long-term biomedical applications because the degradation time is much slower than other polymers. However, the biocompatibility of this polymer and the potential for longer delivery windows renders it a promising polymer candidate for drug delivery. In this work, we outline sixteen emulsion solvent evaporation preparation methods for PCL nanoparticles and microparticles to develop particles between 300 nm and 1.7 μm and with zeta potentials of -1.8 mV. We further investigated particles in a size range suitable for systemic tumor delivery and inhaled aerosol delivery to determine cell biocompatibility with the polymer in lung adenocarcinoma, endometrial adenocarcinoma, and human embryonic kidney cells. We determined these particles aren't detrimental to cell viability below particle monolayer coverage atop cells and therefore these formulations hold promise for the next stage of development as sustained-release drug delivery carriers.

Abstract Image

调节乳液性质会影响用于药物递送应用的聚(己内酯)颗粒的尺寸。
聚合物药物载体的加入加速了药物递送的进展。直接递送到靶位点是开发治疗疾病的有效药物和基因疗法的一个有希望的步骤。这些药物载体的疗效在很大程度上依赖于细胞摄取,而不会损害促进细胞活力的关键细胞过程。可生物降解聚合物的药物释放主要由聚合物降解介导,因此聚合物降解速率决定了药物递送应用的可行性。传统上,聚己内酯(PCL)仅用于长期的生物医学应用,因为其降解时间比其他聚合物慢得多。然而,这种聚合物的生物相容性和更长递送窗口的潜力使其成为药物递送的一种有前途的候选聚合物。在该工作中,我们概述了16种乳液溶剂蒸发制备PCL纳米颗粒和微粒的方法,使其形成300nm至1.7μm的颗粒,ζ电位为-1.8mV。我们进一步研究了适合全身肿瘤递送和吸入气溶胶递送的尺寸范围内的颗粒,以确定肺腺癌中聚合物的细胞生物相容性,子宫内膜腺癌和人胚胎肾细胞。我们确定,在细胞上颗粒单层覆盖率以下,这些颗粒对细胞活力没有损害,因此这些制剂有望作为缓释药物递送载体进入下一阶段。
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来源期刊
AAPS Journal
AAPS Journal 医学-药学
CiteScore
7.80
自引率
4.40%
发文量
109
审稿时长
1 months
期刊介绍: The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists (AAPS), publishes novel and significant findings in the various areas of pharmaceutical sciences impacting human and veterinary therapeutics, including: · Drug Design and Discovery · Pharmaceutical Biotechnology · Biopharmaceutics, Formulation, and Drug Delivery · Metabolism and Transport · Pharmacokinetics, Pharmacodynamics, and Pharmacometrics · Translational Research · Clinical Evaluations and Therapeutic Outcomes · Regulatory Science We invite submissions under the following article types: · Original Research Articles · Reviews and Mini-reviews · White Papers, Commentaries, and Editorials · Meeting Reports · Brief/Technical Reports and Rapid Communications · Regulatory Notes · Tutorials · Protocols in the Pharmaceutical Sciences In addition, The AAPS Journal publishes themes, organized by guest editors, which are focused on particular areas of current interest to our field.
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