title: Ð¡ÑÐ°Ð²Ð½Ð¸ÑÐµÐ»ÑÐ½Ð¾Ðµ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ðµ CaCO3 Ð¸ PLA Ð¼Ð¸ÐºÑÐ¾- Ð¸ Ð½Ð°Ð½Ð¾ÑÐ°ÑÑÐ¸Ñ Ð´Ð»Ñ Ð¿ÐµÑÐ¾ÑÐ°Ð»ÑÐ½Ð¾Ð¹ Ð´Ð¾ÑÑÐ°Ð²ÐºÐ¸ Ð¼Ð¸Ð ÐÐ
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¼Ð°Ð³Ð¸ÑÑÑÐ°
titleType: Subtitle
title: Ð¡omparative investigation of CaCO3 and PLA micro- and nanoparticle siRNA carriers for oral delivery
Creators: name: ÐÐ¶Ð°Ð·ÑÐ»Ð¸, Ð Ð¸Ð¼
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2024
Subjects: Ð¼Ð¸Ð ÐÐ-Ð»ÐµÐºÐ°ÑÑÑÐ²ÐµÐ½Ð½ÑÐµ Ð¿ÑÐµÐ¿Ð°ÑÐ°ÑÑ
n CaCO3
Ð¿ÐµÑÐ¾ÑÐ°Ð»ÑÐ½Ð¾Ðµ Ð²Ð²ÐµÐ´ÐµÐ½Ð¸Ðµ
Ð¶ÐµÐ»ÑÐ´Ð¾ÑÐ½Ð¾-ÐºÐ¸ÑÐµÑÐ½ÑÐ¹ ÑÑÐ°ÐºÑ
ÐÐÐ¢
ÑÐ¸ÑÑÐµÐ¼Ñ Ð´Ð¾ÑÑÐ°Ð²ÐºÐ¸
siRNA-drugs
nPLA
nCaCO3
oral administration
gastrointestinal tract
GIT
delivery systems

description: ÐÐ°Ð»Ð°Ñ Ð¸Ð½ÑÐµÑÑÐµÑÐ¸ÑÑÑÑÐ°Ñ Ð ÐÐ (Ð¼Ð¸Ð ÐÐ) ÑÐ²Ð»ÑÐµÑÑÑ Ð¾Ð´Ð½Ð¸Ð¼ Ð¸Ð· Ð½Ð°Ð¸Ð±Ð¾Ð»ÐµÐµ Ð¼Ð¾ÑÐ½ÑÑ Ð¸Ð½ÑÑÑÑÐ¼ÐµÐ½ÑÐ¾Ð² Ð´Ð»Ñ Ð¿Ð¾Ð´Ð°Ð²Ð»ÐµÐ½Ð¸Ñ ÑÐºÑÐ¿ÑÐµÑÑÐ¸Ð¸ Ð³ÐµÐ½Ð¾Ð², Ð¿ÐµÑÐ¾ÑÐ°Ð»ÑÐ½Ð¾Ðµ Ð²Ð²ÐµÐ´ÐµÐ½Ð¸Ðµ ÐºÐ¾ÑÐ¾ÑÐ¾Ð³Ð¾ ÑÐ¶Ðµ Ð´Ð°Ð²Ð½Ð¾ Ð¸ÑÐ¿Ð¾Ð»ÑÐ·ÑÐµÑÑÑ Ð´Ð»Ñ Ð»ÐµÑÐµÐ½Ð¸Ñ Ð²Ð¾ÑÐ¿Ð°Ð»Ð¸ÑÐµÐ»ÑÐ½ÑÑ Ð¸ Ð¾Ð½ÐºÐ¾Ð³ÐµÐ½Ð½ÑÑ ÑÐ¾ÑÑÐ¾ÑÐ½Ð¸Ð¹ ÐºÐ¸ÑÐµÑÐ½Ð¸ÐºÐ°. ÐÐ´Ð½Ð°ÐºÐ¾ Ð¸Ð·-Ð·Ð° Ð¼Ð½Ð¾Ð³Ð¾ÑÐ¸ÑÐ»ÐµÐ½Ð½ÑÑ Ð±Ð°ÑÑÐµÑÐ¾Ð² Ð²Ð´Ð¾Ð»Ñ Ð¶ÐµÐ»ÑÐ´Ð¾ÑÐ½Ð¾-ÐºÐ¸ÑÐµÑÐ½Ð¾Ð³Ð¾ ÑÑÐ°ÐºÑÐ° (ÐÐÐ¢) Ð´Ð¾ÑÑÐ°Ð²ÐºÐ° Ð¼Ð¸Ð ÐÐ Ð² ÑÐ¿Ð¸ÑÐµÐ»Ð¸Ð¹ ÐºÐ¸ÑÐµÑÐ½Ð¸ÐºÐ° Ð·Ð°ÑÑÑÐ´Ð½ÐµÐ½Ð°. Ð¡ ÑÑÐ¾Ð¹ ÑÐµÐ»ÑÑ Ð±ÑÐ»Ð¸ Ð¿ÑÐ¾Ð²ÐµÐ´ÐµÐ½Ñ ÑÑÐ°Ð²Ð½Ð¸ÑÐµÐ»ÑÐ½ÑÐµ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ Ð¼Ð¸ÐºÑÐ¾- Ð¸ Ð½Ð°Ð½Ð¾ÑÐ°ÑÑÐ¸Ñ Ð½Ð° Ð¾ÑÐ½Ð¾Ð²Ðµ ÐºÐ°ÑÐ±Ð¾Ð½Ð°ÑÐ° ÐºÐ°Ð»ÑÑÐ¸Ñ (CaCO3) Ð¸ Ð¿Ð¾Ð»Ð¸Ð¼Ð¾Ð»Ð¾ÑÐ½Ð¾Ð¹ ÐºÐ¸ÑÐ»Ð¾ÑÑ (PLA), mCaCO3, nCaCO3, mPLA, nPLA, Ð² ÐºÐ¾Ð½ÑÐµÐºÑÑÐµ Ð¿ÐµÑÐ¾ÑÐ°Ð»ÑÐ½Ð¾Ð³Ð¾ Ð²Ð²ÐµÐ´ÐµÐ½Ð¸Ñ Ð¸ Ð´Ð¾ÑÑÐ°Ð²ÐºÐ¸ Ð¼Ð¸Ð ÐÐ Ð² ÐºÐ¸ÑÐµÑÐ½Ð¸Ðº. Ð Ð°Ð·ÑÐ°Ð±Ð¾ÑÐ°Ð½Ð½ÑÐµ Ð½Ð¾ÑÐ¸ÑÐµÐ»Ð¸ Ð±ÑÐ»Ð¸ Ð¸Ð½Ð´Ð¸Ð²Ð¸Ð´ÑÐ°Ð»ÑÐ½Ð¾ Ð¾ÑÐ°ÑÐ°ÐºÑÐµÑÐ¸Ð·Ð¾Ð²Ð°Ð½Ñ Ñ Ð¿Ð¾Ð¼Ð¾ÑÑÑ ÑÐ»ÐµÐºÑÑÐ¾Ð½Ð½Ð¾Ð¹ Ð¼Ð¸ÐºÑÐ¾ÑÐºÐ¾Ð¿Ð¸Ð¸, Ð¿ÑÐ¾ÑÐµÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ñ Ð½Ð° ÑÑÐ°Ð±Ð¸Ð»ÑÐ½Ð¾ÑÑÑ Ð¸ ÑÐ´ÐµÑÐ¶Ð°Ð½Ð¸Ðµ Ð¼Ð¸Ð ÐÐ Ð² Ð¼Ð¾Ð´ÐµÐ»Ð¸ÑÑÐµÐ¼ÑÑ Ð¶ÐµÐ»ÑÐ´Ð¾ÑÐ½Ð¾-ÐºÐ¸ÑÐµÑÐ½ÑÑ Ð¶Ð¸Ð´ÐºÐ¾ÑÑÑÑ (SGIF) Ñ Ð¿Ð¾Ð¼Ð¾ÑÑÑ ÑÐ»ÐµÐºÑÑÐ¾ÑÐ¾ÑÐµÐ·Ð°. ÐÐ°Ð»ÑÐ½ÐµÐ¹ÑÐ¸Ðµ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ ÐºÐ»ÐµÑÐ¾ÑÐ½Ð¾Ð¹ Ð°ÑÑÐ¾ÑÐ¸Ð°ÑÐ¸Ð¸ Ð¸ Ð¿Ð¾Ð³Ð»Ð¾ÑÐµÐ½Ð¸Ñ, Ð° ÑÐ°ÐºÐ¶Ðµ Ð±Ð¸Ð¾ÑÐ°ÑÐ¿ÑÐµÐ´ÐµÐ»ÐµÐ½Ð¸Ñ in vitro Ð¸ in vivo Ð±ÑÐ»Ð¸ Ð¿ÑÐ¾Ð²ÐµÐ´ÐµÐ½Ñ Ð½Ð° ÐºÐ»ÐµÑÐºÐ°Ñ Caco-2 Ð¸ Ð¼ÑÑÐ°Ñ Ð»Ð¸Ð½Ð¸Ð¸ BALB/C Ñ Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°Ð½Ð¸ÐµÐ¼ Ð¼ÐµÑÐ¾Ð´Ð¾Ð² Ð¿ÑÐ¾ÑÐ¾ÑÐ½Ð¾Ð¹ ÑÐ¸ÑÐ¾Ð¼ÐµÑÑÐ¸Ð¸, ÐºÐ¾Ð½ÑÐ¾ÐºÐ°Ð»ÑÐ½Ð¾Ð¹ Ð¼Ð¸ÐºÑÐ¾ÑÐºÐ¾Ð¿Ð¸Ð¸, Ð²Ð¸Ð·ÑÐ°Ð»Ð¸Ð·Ð°ÑÐ¸Ð¸ ex-vivo, Ð¾Ð´Ð½Ð¾ÑÐ¾ÑÐ¾Ð½Ð½Ð¾Ð¹ ÑÐ¾Ð¼Ð¾Ð³ÑÐ°ÑÐ¸Ð¸ Ð¸ Ð³Ð¸ÑÑÐ¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ñ Ð°Ð½Ð°Ð»Ð¸Ð·Ð¾Ð². Ð ÐµÐ·ÑÐ»ÑÑÐ°ÑÑ Ð¿Ð¾ÐºÐ°Ð·Ð°Ð»Ð¸, ÑÑÐ¾ ÑÐ¸Ð·Ð¸ÐºÐ¾-ÑÐ¸Ð¼Ð¸ÑÐµÑÐºÐ¸Ðµ ÑÐ²Ð¾Ð¹ÑÑÐ²Ð° ÑÐ°ÑÑÐ¸Ñ, Ð³Ð»Ð°Ð²Ð½ÑÐ¼ Ð¾Ð±ÑÐ°Ð·Ð¾Ð¼ Ð¸Ñ ÑÐ°Ð·Ð¼ÐµÑ Ð¸ Ð¿Ð¾Ð²ÐµÑÑÐ½Ð¾ÑÑÐ½ÑÐ¹ Ð·Ð°ÑÑÐ´, Ð·Ð½Ð°ÑÐ¸ÑÐµÐ»ÑÐ½Ð¾ Ð²Ð»Ð¸ÑÑÑ Ð½Ð° Ð¸Ñ Ð±Ð¸Ð¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¾Ðµ ÑÐ°ÑÐ¿ÑÐµÐ´ÐµÐ»ÐµÐ½Ð¸Ðµ. ÐÐ°Ð¸Ð»ÑÑÑÐ¸Ðµ ÑÐµÐ·ÑÐ»ÑÑÐ°ÑÑ Ð¿Ð¾ÐºÐ°Ð·Ð°Ð»Ð¸ ÑÐ°ÑÑÐ¸ÑÑ, Ð±Ð»Ð¸Ð·ÐºÐ¸Ðµ Ðº Ð½ÐµÐ¹ÑÑÐ°Ð»ÑÐ½ÑÐ¼ Ð¸ Ð¼ÐµÐ½ÑÑÐµÐ³Ð¾ ÑÐ°Ð·Ð¼ÐµÑÐ°. Ð Ð·Ð°ÐºÐ»ÑÑÐµÐ½Ð¸Ðµ, ÑÑÐµÐ´Ð¸ ÑÐ°ÑÑÐ¸Ñ nPLA Ð±ÑÐ»Ð° Ð¾Ð¿ÑÐµÐ´ÐµÐ»ÐµÐ½Ð° ÐºÐ°Ðº Ð½Ð°Ð¸Ð±Ð¾Ð»ÐµÐµ ÑÑÑÐµÐºÑÐ¸Ð²Ð½ÑÐ¹ Ð¿ÐµÑÐ¾ÑÐ°Ð»ÑÐ½ÑÐ¹ Ð¿ÐµÑÐµÐ½Ð¾ÑÑÐ¸Ðº Ð¼Ð¸Ð ÐÐ Ð² ÐÐÐ¢, Ð¾Ð´Ð½Ð°ÐºÐ¾ Ð½ÐµÐ¾Ð±ÑÐ¾Ð´Ð¸Ð¼Ñ Ð´Ð°Ð»ÑÐ½ÐµÐ¹ÑÐ¸Ðµ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ Ð´Ð»Ñ Ð¾ÑÐµÐ½ÐºÐ¸ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ð¼Ð¸Ð ÐÐ Ð¸ Ð¾Ð¿ÑÐ¸Ð¼Ð¸Ð·Ð°ÑÐ¸Ð¸ Ð´Ð¾ÑÑÐ°Ð²ÐºÐ¸.
description: Small interfering RNA (siRNA) is one of the most powerful tools for gene expression downregulation, and the oral administration of which has long been sought to treat intestinal inflammatory and oncogenic conditions. However, due to the multiples barriers along the gastrointestinal tract (GIT), it is difficult to deliver siRNA into the intestinal epithelium. To this end, calcium carbonate (CaCO3) and polylactic acid (PLA) based micro- and nanoparticles, mCaCO3, nCaCO3, mPLA, nPLA, were comparatively investigated in the context of oral administration and delivery of siRNA into the intestines. The developed carriers were individually characterized by electron microscopy, tested for stability and siRNA retention in simulated gastrointestinal fluids (SGIF) by electrophoresis. Further in vitro and in vivo studies of cellular association and uptake, as well as bio-distribution were carried on Caco-2 cells, and BALB/C mice, using flow cytometry, confocal microscopy, ex-vivo bioimaging, single-photon tomography methods, and histological analyses. The results revealed that the physicochemical properties of the particles, mainly their size, and surface charge, considerably affect their biodistribution profiles. With those being close to neutral, and smaller in size performing best. In conclusion, among the particles, nPLA had been determined as the most effecient oral delivery-carrier for siRNA to the GIT, however, further investigations should be made to evaluate siRNA activity and optimize delivery.