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Development of Ophthalmic Formulations
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Paramita Sarkar, Martin Coffey, Mohannad Shawer
Retinal vessels are supplied by the central retinal vessel. Retinal capillaries are composed of a single layer of endothelial cells surrounded by a basement membrane and pericytes. The endothelial cells are attached to each other by tight junctions forming the inner blood–retina barrier. These narrow tight junctions, similar to those present in the brain vessels, impair the paracellular transport of hydrophilic compounds and necessitate their passage through the intracellular routes [26].
Microplastics and human health: Integrating pharmacokinetics
Published in Critical Reviews in Environmental Science and Technology, 2023
The main routes of exposure to microplastics for humans consist of ingestion, inhalation, and dermal contact. The digestive system is important in the digestion and absorption of nutrients and electrolytes, which occur mainly in the small intestine. The small intestine may also play an important role in the absorption of microplastics (Figure 1). Contact of microplastics with the intestinal mucosa is dependent on their ability to cross the intestinal mucus, facilitated through a formation of a corona of organic matter or intestinal contents (Powell et al., 2007) or due to small particle sizes (Szentkuti, 1997). After crossing the intestinal mucus, particles come in contact with the intestinal epithelium, being internalized by the following mechanisms: (i) transcytosis, the uptake and transport of smaller particles by enterocytes; (ii) internalization by M cells (e.g. micropinocytosis, phagocytosis, and receptor-mediated endocytosis) or other cells in the intestinal mucosa adjacent to Peyer’s patches; (iii) paracellular transport, through gaps between cells dependent on concentration gradients and particle sizes, increasing when tight junction integrity is compromised; (iv) persorption through gaps in the villi during cell turnover (desquamation zones), openings of tight junctions during the migration of macrophages, or damage to the epithelium (e.g. erosion and ulceration), for larger particles (e.g. 7–70 µm); (v) uptake by migratory phagocytes (e.g. intestinal macrophages and dendritic cells) directly from the intestinal lumen (Delon et al., 2022).
Biopolymeric nanocarrier: an auspicious system for oral delivery of insulin
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Suchitra Kumari Panigrahy, Awanish Kumar
The translocation mechanism of nanocarriers in the intestinal epithelium involves either paracellular or transcellular transport.a) Paracellular pathway: It is the preferred route for the transport of hydrophilic drugs. However tight junction between the epithelial cells restricts or blocks the passage of macromolecules or particles larger than 1 nm [5]. Therefore, as is widely recognized, polymeric NPs cannot diffuse through the intestinal barrier via the paracellular route. So to enhance paracellular transport of nanocarriers, tight junctions opened reversibly by using permeation enhancers such as cationic (Chitosan and its derivatives) and anionic (polyacrylic acid and its derivatives) polymers or calcium chelators [82]. The cationic and anionic polymers disassemble tight junctions whereas calcium chelators disrupt adherence and tight junctions by activating protein kinase C [71]. But it still limits the transport of nanoparticles larger than 20 nm into the bloodstream [96].b) Transcellular pathway: Nanocarriers can be taken up by enterocytes or M cells of Peyer’s patches in this pathway by overcoming pre-systemic hepatic metabolism leading to increased drug bioavailability. Due to their larger size nanocarriers cannot diffuse through cells by passive diffusion. So the active transcellular transport begins with an endocytic process that occurs at the apical cell membrane; then the particles are transported through the cells and release at their basolateral pole [13].