Mechanistic Approaches of Internalization, Subcellular Trafficking, and Cytotoxicity of Nanoparticles for Targeting the
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Review Article Mechanistic Approaches of Internalization, Subcellular Trafficking, and Cytotoxicity of Nanoparticles for Targeting the Small Intestine Asadullah Madni,1,4 Sadia Rehman,1 Humaira Sultan,1 Muhammad Muzamil Khan,1 Faiz Ahmad,2 M. Rafi Raza,3 Nadia Rai,1 and Farzana Parveen1
Received 24 July 2020; accepted 5 November 2020 Abstract. Targeting the small intestine employing nanotechnology has proved to be a more effective way for site-specific drug delivery. The drug targeting to the small intestine can be achieved via nanoparticles for its optimum bioavailability within the systemic circulation. The small intestine is a remarkable candidate for localized drug delivery. The intestine has its unique properties. It has a less harsh environment than the stomach, provides comparatively more retention time, and possesses a greater surface area than other parts of the gastrointestinal tract. This review focuses on elaborating the intestinal barriers and approaches to overcome these barriers for internalizing nanoparticles and adopting different cellular trafficking pathways. We have discussed various factors that contribute to nanocarriers’ cellular uptake, including their surface chemistry, surface morphology, and functionalization of nanoparticles. Furthermore, the fate of nanoparticles after their uptake at cellular and subcellular levels is also briefly explained. Finally, we have delineated the strategies that are adopted to determine the cytotoxicity of nanoparticles. KEY WORDS: targeted drug delivery; nanocarriers; small intestine; intestinal barriers; cellular trafficking; cytotoxicity.
INTRODUCTION The oral route is always considered the appropriate and reliable pathway for delivering therapeutic agents due to increased patient compliance, particularly in chronic illness. It ensures convenience, facilitates self-administration, and offers excellent flexibility in dosage regimen as the highly sterile conditions are not required for oral products, their manufacture leading to a decline in production costs (1). Moreover, the oral route seems to have interesting physiological reasons as the surface area (300–400 m) of the gastrointestinal tract (GIT) is extensive for drug absorption through absorptive epithelial cells (2–6). Despite the numerous advantages of oral delivery, it also possesses some drawbacks such as drug requires crossing manifold compartments of the human body before it reaches the systemic circulation, which is a challenging task (7). Furthermore, after ingestion, the drug faces the harsh acidic pH of the stomach before it arrives at the small intestine via 1
Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan. 2 Departments of Mechanical Engineering, Universiti Teknologi PETRONAS, Seri Iskandar, Malaysia. 3 Department of Mechanical Engineering, COMSATS University Islamabad, Sahiwal Campus, Sahiwal, Pakistan. 4 To whom correspondence should be addressed. (e–mail: [email protected])
the duodenum, which is said to be the central enzymatic digestion machi
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