Sustained Nano Systems, Long Island High Technology Incubator, Stony Brook, NY, USA.
Transl Vis Sci Technol. 2023 Mar 1;12(3):28. doi: 10.1167/tvst.12.3.28.
To demonstrate that a single administration of an anti-angiogenic monoclonal antibody, when integrated into a novel biodegradable Densomere composed only of the active pharmaceutical ingredient and polymer, maintains molecular integrity, sustained release, and prolonged bioactivity in vitro and in vivo for up to 12 months.
Bevacizumab, a high-molecular-weight antibody (140,000-150,000 Da) was incorporated at 5% loading into Densomere microparticle carriers (DMCs) for injection to observe in vitro release over time from an aqueous suspension. The molecular integrity of the released bevacizumab was assessed by enzyme-linked immunosorbent assay (ELISA) and size-exclusion chromatography-high-performance liquid chromatography (SEC-HPLC). Anti-angiogenic bioactivity in vivo was assessed using the rabbit corneal suture model for suppression of neovascular encroachment from the limbus following a single subconjunctival administration.
Continuous release of bevacizumab in vitro was observed in serial samples over a period of 12 months. ELISA and SEC-HPLC yielded profiles from aqueous supernatant samples indistinguishable from the reference bevacizumab. A single subconjunctival administration in rabbit eyes significantly suppressed corneal neovascularization in vivo compared to control eyes for 12 months.
The Densomere carrier platform maintained the molecular integrity of bevacizumab with a prolonged release profile in vitro and demonstrated sustained in vivo drug delivery with continuous bioactivity in the rabbit cornea eye model for 12 months.
The Densomere platform provides a significant opportunity for prolonged delivery of biologics in ocular and other tissues.
展示在新型可生物降解的 Densomere 中单次给予抗血管生成单克隆抗体，当仅由活性药物成分和聚合物组成时，可保持分子完整性、持续释放和延长体外和体内长达 12 个月的生物活性。
将贝伐单抗（一种高分子量抗体（140,000-150,000Da））以 5%的载药量掺入 Densomere 微球载体（DMC）中，用于观察从水性混悬液中随时间的体外释放。通过酶联免疫吸附测定（ELISA）和尺寸排阻色谱-高效液相色谱（SEC-HPLC）评估释放的贝伐单抗的分子完整性。通过单次结膜下给药抑制从角膜缘向角膜内侵入的兔角膜缝合模型评估体内抗血管生成的生物活性。
在 12 个月的时间内，在连续的样本中观察到贝伐单抗的持续释放。从水性上清液样品中获得的 ELISA 和 SEC-HPLC 图谱与参比贝伐单抗无法区分。与对照眼相比，单次结膜下给药在兔眼内显著抑制了角膜新生血管形成，持续 12 个月。
Densomere 载体平台在体外保持了贝伐单抗的分子完整性，具有延长的释放曲线，并在兔角膜眼模型中展示了持续的体内药物输送，持续 12 个月具有持续的生物活性。
医疗与制药
