  Citation: Hathout, R.M. Do Polymeric Nanoparticles Really Enhance the Bioavailability of Oral Drugs? A Quantitative Answer Using Meta-Analysis. Gels 2022, 8, 119. https://doi.org/10.3390/ gels8020119 Academic Editor: Alejandro Sosnik Received: 30 January 2022 Accepted: 12 February 2022 Published: 14 February 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). gels Article Do Polymeric Nanoparticles Really Enhance the Bioavailability of Oral Drugs? A Quantitative Answer Using Meta-Analysis Rania M. Hathout Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt; rania.hathout@pharma.asu.edu.eg or r_hathout@yahoo.com Abstract: The oral route remains one of the most popular and important routes of administration for drugs—one that warrants the development of advanced drug delivery systems, such as polymeric nanoparticles capable of enhancing the absorption and bioavailability of the used drugs. In this work, a systematic review of published works on several databases, followed by a meta-analysis, were utilized in order to navigate the published studies and access literature-based evidence about the capability of polymeric nanoparticulate systems to augment the absorption and bioavailability of orally administered drugs. The pharmacokinetic parameter of the area under the curve (AUC) was utilized as the “effect” of this meta-analytical study. The meta-analysis demonstrated a significant increase in AUC compared to conventional formulations. Furthermore, comparing the synthetic polymeric nanoparticles, versus their naturally-based administered counterparts, as subgroups of the meta-analysis, revealed no significant differences. Keywords: oral; drugs; nanoparticles; polymers; systematic; meta-analysis 1. Introduction The oral route remains the most common route of drug administration and one of the most convenient and acceptable to patients, due to its non-invasiveness and ease of administration [1]. It is also preferred by the pharmaceutical industry due to the feasibility of its mass production [2]. Several attempts have been made in order to enhance the bioavailability of orally administered drugs and increase their absorption. Encapsulating the drugs in different lipid and polymeric nanoparticles (NP) is one example of these attempts [3,4]. Moreover, the delivery of drugs in a controlled manner is currently a topic of great importance for both the industry and academia, due to its huge benefits for health- care [5]. Recently, the use of lipid-based nano-carriers has shown proven superiority over the conventional formulations in augmenting the bioavailability of oral drugs, via a study using quantitative meta-analysis [6]. The close affinity of those carriers with the lipidic nature of intestinal cell membranes may have contributed to this outcome. Consequently, a logical question arises whether or not the use of polymeric nanoparticles increases the bioavailability of the aforementioned drugs, bearing in mind their different nature and more rigid matrices. From the pharmaceutical point of view, polymeric nanoparticles are of special interest as they are more stable than other lipidic nanocarriers, such as liposomes, and impart more protective effects to their internal cargo [7–9]. Furthermore, they are distinguished by their facile modulation regarding their size, hydrophobicity, and surface grafting and conjugation [10–13]. Accordingly, the same informatics tools of systematic reviewing and meta-analysis are utilized in this study to answer this question. Systematic reviewing deals with the synthesis of empirical evidence according to pre-specified eligibility criteria, in order to address a specific research question. On the one hand, this method is considered a qualitative informatics tool, while on the other hand, meta-analysis is a quantitative synthesis tool [14]. Meta-analysis is an advanced statistical method that integrates data extracted from multiple studies originating from Gels 2022, 8, 119. https://doi.org/10.3390/gels8020119 https://www.mdpi.com/journal/gels