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Drug Targeting to the Lung: Chemical and Biochemical Considerations
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Peter A. Crooks, Narsimha R. Penthala, Abeer M. Al-Ghananeem
Enhancement of drug uptake by altered junctional (paracellular) or vesicular (transcellular) transport (Figure 3.2) is an active area of research. The paracellular transport mechanism provides an explanation for the pulmonary absorption of peptides and proteins ≤ 40 kDa.
Gastrointestinal Tract as a Major Route of Pharmaceutical Administration
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
Substances entering the cellular membrane via the transcellular route do so either passively or are actively transported. There are several types of transcellular transport processes including those that are completely passive, those that are active and those that do not fit into either category.
Evaluation Methods for Conditioned Hair
Published in E. Desmond Goddard, James V. Gruber, Principles of Polymer Science and Technology in Cosmetics and Personal Care, 1999
E. Desmond Goddard, James V. Gruber
Intercellular, as opposed to transcellular, transport is especially important for the incorporation of larger molecules such as polymeric materials into the cuticle, or even more so for diffusion into the cortex. The intercellular cement is thought to contain nonkeratinous, low-sulfur proteins, which are high in polar amino acids and are assumed to swell
Evaluating the safety profile of focused ultrasound and microbubble-mediated treatments to increase blood-brain barrier permeability
Published in Expert Opinion on Drug Delivery, 2019
Dallan McMahon, Charissa Poon, Kullervo Hynynen
Currently, strategies to circumvent the BBB for the delivery of therapeutics rely on altering paracellular transport (e.g. hyperosmotic solutions [8]), transcellular transport (e.g. carrier protein-mediated transport [9]), or on utilizing delivery routes outside of the circulatory system (e.g. intracranial injections [10], intranasal delivery [11], hydrogels [12]). Although hyperosmotic solutions may be helpful for neurological diseases that require treating large volumes of brain tissue, the use of such reagents can lead to structural alterations to neurons, lesions, macrophage accumulation, and glial activation [13]. Other strategies for bypassing the BBB suffer from their invasive nature, non-targeted delivery, or non-therapeutically relevant concentrations of drug delivery.
Overview of intranasally delivered peptides: key considerations for pharmaceutical development
Published in Expert Opinion on Drug Delivery, 2018
Wisam Al Bakri, Maureen D. Donovan, Maria Cueto, Yunhui Wu, Chinedu Orekie, Zhen Yang
Along with MW, the size and shape of peptide molecules also affect the uptake of peptides across the nasal mucosa. McMartin et al. reported that cyclic molecules with smaller molecular radii have an improved absorption compared with linear molecules. The same investigators suggested that the transport of polar molecules could occur in three possible ways: 1) transcytosis, which involves uptake into vesicles formed along the cell membrane; 2) transcellular transport, which includes passive partitioning and carrier-mediated transport across the cell membrane; and 3) paracellular transport through the tight junctions [13,42]. Endocytotic vesicles range in size from about 60 nm (600 Å) to a few microns [43,44], and therefore can participate in the uptake of large molecules such as peptides. Richard et al. reported that wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) (MW 38,000 Da) delivered intranasally is endocytosed by the olfactory neurons [45]. Balin et al. observed that WGA-HRP administered intranasally passes freely through the paracellular spaces within 45–90 min [46]. McMartin suggested that paracellular transport through the tight junctions is one of the most important uptake pathways through which peptides are absorbed across the nasal epithelium [13].
Low colonic absorption drugs: risks and opportunities in the development of oral extended release products
Published in Expert Opinion on Drug Delivery, 2018
Jin Xu, Yiqing Lin, Pierre Boulas, Matthew L. Peterson
Generally, transcellular transport is considered the main absorption route for orally administered drugs with lipophilicity of Log P > 0 and MW > 300 g/mole [27,28]. The optimal partition coefficient (log P) for compounds to diffuse through lipophilic membrane falls within the range of 2–7 [29]. For drugs absorbed by both paracellular and transcellular routes, typically transcellular transport is more important since the tight junction is less than 1% of the entire surface area of the mucosa [3]. Even if the compound is the substrate of intestinal transporter, transcellular diffusion might still be the main absorption route for the compounds with suitable physicochemical properties [30].