Batista Patrícia, Castro Pedro, Madureira Ana Raquel, Sarmento Bruno, Pintado Manuela
Escola Superior de Biotecnologia, Centro de Biotecnologia e Química Fina, Rua Arquiteto Lobão Vital, 172, 4200-374 Porto, Portugal.
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra-PRD, Portugal.
Pharmaceuticals (Basel). 2019 Feb 20;12(1):32. doi: 10.3390/ph12010032.
Nowadays, bioactive peptides are used for therapeutic applications and the selection of a carrier to deliver them is very important to increase the efficiency, absorption, release, bioavailability and consumer acceptance. The aim of this study was to develop and characterize chitosan-based films loaded with chitosan microparticles containing a bioactive peptide (sequence: KGYGGVSLPEW) with antihypertensive properties. Films were prepared by the solvent casting method, while the microparticles were prepared by ionic gelation. The final optimized chitosan microparticles exhibited a mean diameter of 2.5 µm, a polydispersity index of 0.46, a zeta potential of +61 mV and a peptide association efficiency of 76%. Chitosan films were optimized achieving the final formulation of 0.79% (/) of chitosan, 6.74% (/) of sorbitol and 0.82% (/) of citric acid. These thin (±0.100 mm) and transparent films demonstrated good performance in terms of mechanical and biological properties. The oral films developed were flexible, elastic, easy to handle and exhibited rapid disintegration (30 s) and an erosion behavior of 20% when they came into contact with saliva solution. The cell viability (75⁻99%) was proved by methylthiazolydiphenyl-tetrazolium bromide (MTT) assay with TR146 cells. The chitosan mucoadhesive films loaded with peptide⁻chitosan microparticles resulted in an innovative approach to perform administration across the buccal mucosa, because these films present a larger surface area, leading to the rapid disintegration and release of the antihypertensive peptide under controlled conditions in the buccal cavity, thus promoting bioavailability.
如今，生物活性肽被用于治疗应用，选择一种载体来递送它们对于提高效率、吸收、释放、生物利用度和消费者接受度非常重要。本研究的目的是开发并表征负载含有具有降压特性的生物活性肽（序列：KGYGGVSLPEW）的壳聚糖微粒的壳聚糖基薄膜。薄膜通过溶液浇铸法制备，而微粒通过离子凝胶法制备。最终优化的壳聚糖微粒平均直径为2.5 µm，多分散指数为0.46，zeta电位为+61 mV，肽结合效率为76%。壳聚糖薄膜经过优化，最终配方为0.79%（/）的壳聚糖、6.74%（/）的山梨醇和0.82%（/）的柠檬酸。这些薄（±0.100 mm）且透明的薄膜在机械和生物学性能方面表现良好。所开发的口腔薄膜柔韧性好、有弹性、易于处理，与唾液溶液接触时表现出快速崩解（30秒）和20%的侵蚀行为。通过用TR146细胞进行的甲基噻唑基二苯基溴化四氮唑（MTT）试验证明了细胞活力（75⁻99%）。负载肽⁻壳聚糖微粒的壳聚糖粘膜粘附薄膜为经颊粘膜给药提供了一种创新方法，因为这些薄膜具有更大的表面积，导致降压肽在口腔中可控条件下快速崩解和释放，从而提高生物利用度。
