The oral route is the most common route for drug administration. It is the most preferred route, due to its advantages, such as non-invasiveness, patient compliance and convenience of drug administration. Various factors govern oral drug absorption including drug solubility, mucosal permeability, and stability in the gastrointestinal tract environment. Attempts to overcome these factors have focused on understanding the physicochemical, biochemical, metabolic and biological barriers which limit the overall drug bioavailability. Different pharmaceutical technologies and drug delivery systems including nanocarriers, micelles, cyclodextrins and lipid-based carriers have been explored to enhance oral drug absorption. To this end, this review will discuss the physiological, and pharmaceutical barriers influencing drug bioavailability for the oral route of administration, as well as the conventional and novel drug delivery strategies. The challenges and development aspects of pediatric formulations will also be addressed.

Nuxia oppositifolia is traditionally used in diabetes treatment in many Arabian countries; however, scientific evidence is lacking. Hence, the present study explored the antidiabetic and antioxidant activities of the plant extracts and their purified compounds. The methanolic crude extract of N. oppositifolia was partitioned using a two-solvent system. The n-hexane fraction was purified by silica gel column chromatography to yield several compounds including katononic acid and 3-oxolupenal. Antidiabetic activities were assessed by α-amylase and α-glucosidase enzyme inhibition. Antioxidant capacities were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) scavenging assays. Further, the interaction between enzymes (α-amylase and α-glucosidase) and ligands (3-oxolupenal and katononic acid) was followed by fluorescence quenching and molecular docking studies. 3-oxolupenal and katononic acid showed IC₅₀ values of 46.2 μg/mL (101.6 µM) and 52.4 μg/mL (119.3 µM), respectively against the amylase inhibition. 3-oxolupenal (62.3 µg/mL or 141.9 μM) exhibited more potent inhibition against α-glucosidases compared to katononic acid (88.6 µg/mL or 194.8 μM). In terms of antioxidant activity, the relatively polar crude extract and n-butanol fraction showed the greatest DPPH and ABTS scavenging activity. However, the antioxidant activities of the purified compounds were in the low to moderate range. Molecular docking studies confirmed that 3-oxolupenal and katononic acid interacted strongly with the active site residues of both α-amylase and α-glucosidase. Fluorescence quenching results also suggest that 3-oxolupenal and katononic acid have a good affinity towards both α-amylase and α-glucosidase enzymes. This study provides preliminary data for the plant’s use in the treatment of type 2 diabetes mellitus.

Lignin nanoparticles (LNPs) were prepared with the objective of evaluating their application as a novel oral drug delivery system. Curcumin, a polyphenolic natural compound, was used as a lipophilic drug model, as its poor solubility and low oral bioavailability limit its therapeutic efficacy. Optimized nanoparticles were prepared using phase separation and stabilized by citric acid crosslinking. Physicochemical properties of the prepared curcumin-loaded nanoparticles, including particle size, size distribution, morphology, and encapsulation efficiency were characterized. The average particle diameter of curcumin-loaded LNPs was 104 nm, whereas the encapsulation efficiency of curcumin in the nanoparticles was 92%. Stability analyses of curcumin-loaded nanoparticles demonstrated enhanced protection of the entrapped curcumin under storage conditions. Furthermore, in vitro release assays revealed that curcumin-loaded LNPs have high stability in simulated gastric fluid and slow release under intestinal conditions as desirable. To evaluate absorption and bioavailability, we also investigated cellular uptake and transepithelial permeability of curcumin-loaded LNPs using Caco-2 cell monolayers. Cell viability studies revealed that curcumin-loaded LNPs did not induce toxicity in Caco-2 cells. The nanoparticle formulation enhanced curcumin cellular uptake and intestinal permeation compared to free curcumin. Incubation of LNPs on a Caco-2 cell monolayer led to a fivefold increase in apparent permeability compared to free curcumin. Furthermore, in vivo pharmacokinetics experiments showed that the LNP system increased the bioavailability of curcumin by ten-fold compared with the administration of unformulated curcumin. Overall, our findings indicate that the novel LNPs have great potential to be applied as an effective oral drug delivery system, especially for drug molecules with low solubility and limited bioavailability.

Due to their inexpensive and eco-friendly nature, and existence of manganese in various oxidation states and their natural abundance have attained significant attention for the formation of Mn3O4 nanoparticles (Mn3O4 NPs). Herein, we report the preparation of Mn3O4 nanoparticles using manganese nitrate as a precursor material by utilization of a precipitation technique. The as-prepared Mn3O4 nanoparticles (Mn3O4 NPs) were characterized by using X-ray powder diffraction (XRD), UV–Visible spectroscopy (UV–Vis), High-Resolution Transmission electron microscopy (HRTEM), Field emission scanning electron microscopy (FESEM), Thermal gravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FT-IR). The antimicrobial properties of the as-synthesized Mn3O4 nanoparticles were investigated against numerous bacterial and fungal strains including S. aureus, E. coli, B. subtilis, P. aeruginosa, A. flavus and C. albicans. The Mn3O4 NPs inhibited the growth of S. aureus with a minimum inhibitory concentration (MIC) of 40 μg/ml and C. albicans with a MIC of 15 μg/ml. Furthermore, the Mn3O4 NPs anti-cancer activity was examined using MTT essay against A549 lung and MCF-7 breast cancer cell lines. The Mn3O4 NPs revealed significant activity against the examined cancer cell lines A549 and MCF-7. The IC50 values of Mn3O4 NPs with A549 cell line was found at concentration of 98 µg/mL and MCF-7 cell line was found at concentration of 25 µg/mL.