Injectable peptides such as insulin, glucagon-like peptide 1 (GLP-1), and their agonists are being increasingly used for the treatment of diabetes. Currently, the most common route of administration is injection, which is linked to patient discomfort as well as being subjected to refrigerated storage and the requirement for efficient supply chain logistics. Buccal and sublingual routes are recognized as valid alternatives due to their high accessibility and easy administration. However, there can be several challenges, such as peptide selection, drug encapsulation, and delivery system design, which are linked to the enhancement of drug efficacy and efficiency. By using hydrophobic polymers that do not dissolve in saliva, and by using neutral or positively charged nanoparticles that show better adhesion to the negative charges generated by the sialic acid in the mucus, researchers have attempted to improve drug efficiency and efficacy in buccal delivery. Furthermore, unidirectional films and tablets seem to show the highest bioavailability as compared to sprays and other buccal delivery vehicles. This advantageous attribute can be attributed to their capability to mitigate the impact of saliva and inadvertent gastrointestinal enzymatic digestion, thereby minimizing drug loss. This is especially pertinent as these formulations ensure a more directed drug delivery trajectory, leading to heightened therapeutic outcomes. This communication describes the current state of the art with respect to the creation of nanoparticles containing peptides such as insulin, glucagon-like peptide 1 (GLP-1), and their agonists, and theorizes the production of mucoadhesive unidirectional release buccal tablets or films. Such an approach is more patient-friendly and can improve the lives of millions of diabetics around the world; in addition, these shelf-stable formulations ena a more environmentally friendly and sustainable supply chain network.

Curcumin is a major bioactive component present in turmeric, attributed with a bright yellow color; however, with low solubility and susceptibility to photooxidation, many of the purported health benefits are actually limited. We developed an encapsulation delivery system to produce curcumin nanoparticles using α-cyclodextrin as a carrier and Tween 80 as a surfactant for the purpose of increasing photostability and bioavailability. We used RSM to determine an optimal curcumin nanoparticle (NP) size of 386.4 ± 21.3 nm and entrapment efficiency of 97.4 ± 2.9% for use in functional tests conducted in differentiated Caco-2 cells. Curcumin-NP showed greater (p = 0.001) (74.32 ± 4.20%) stability compared to free curcumin (36.74 ± 3.03%), after treatment with pulsed light, at the highest 20 J/cm² energy input. The release behavior of curcumin-NPs was pH-dependent and showed a 5 times higher intestinal epithelial cellular uptake and 21.3% decrease of TEER-value, compared to free curcumin (p = 0.017). Compared with free curcumin, the curcumin-NPs had higher antioxidant capacity in all tests while exhibited lower antioxidant capacity loss after pulsed light treatment. Moreover, pre-exposure of curcumin-NPs to pulsed light treatment showed no apparent cytotoxicity effects in Caco-2 cells. In conclusion, using α-cyclodextrin for curcumin-NP encapsulation enhanced both bioavailability and photostability, leading to greater intestinal intracellular antioxidant capacity and no loss in cell viability.

COVID-19 infection continues globally with frequent emergence of unfamiliar SARS-CoV-2 variants acting to impair immunity conferred by vaccines. The competitive binding of SARS-CoV-2 spike proteins by angiotensin-converting enzyme 2 (ACE-2) to mimetic and act as a de-coy over that by native ACE-2 receptors on healthy human cells re-mains a practical approach to lessen viral spread. In this study, a therapeutic strategy was developed that targeted gastrointestinal SARS-CoV-2 infection using ACE-2 encapsulated in chi-tosan/tripolyphosphate cross-linked nanoparticles (NPs). Optimization conditions were determined by varying pH (4.0-6.5) and chitosan: ACE-2 mixing ratios (1:1, 1.5:1, 2:1, 2.5:1, 3:1), followed by choice of spray-drying (SD), freeze-drying (FD), or spray-freeze drying (SFD) with varying mannitol concentrations (0, 1:1, and 5:1 of total weight). The optimal formulation was achieved using a pH 5.5 with a mixing chitosan-ACE-2 ratio of 2:1; where ACE-2 loaded NPs had an average particle size of 303.7 nm, polydispersity index (PDI) of 0.21, encapsula-tion efficiency (EE) of 98.4%, zeta potential of 6.8 mV, and ACE-2 loading content (LC) of 28.4%. In general, all drying methods main-tained the spherical shape of the NPs with varying mannitol concen-tration having a significant (P<0.05) effect. After reconstitution, all SD samples had a relatively low yield rate, but the ACE-2 NPs dehydrated specifically by SFD required a lower amount of added mannitol (1:1 of its total weight) and produced a higher yield rate (P<0.05) and similar PDI and EE values, along with relatively good particle size and LC. This formulation also produced a high ACE-2 release and uptake in differentiated Caco-2 cells; thus, representing an effective ACE-2 en-capsulation procedure for use with dry powders.

Background/Objectives: COVID-19 infection continues globally, with frequent emergence of unfamiliar SARS-CoV-2 variants acting to impair immunity. The competitive binding of SARS-CoV-2 spike proteins and angiotensin-converting enzyme 2 (ACE-2) can decrease the binding of the virus on native ACE-2 receptors on healthy human cells. It remains a practical approach to lessen viral spread. In this study, a method to encapsulate ACE-2 in the form of chitosan/tripolyphosphate cross-linked nanoparticles (NPs) was developed with emphasis placed on the best dehydration method to secure functional ACE-2 nanoparticles. Methods: Methods: Preparation conditions were assessed by varying pH (4.0–6.5) and the ratio between chitosan and ACE-2 mixing ratios (1:1, 1.5:1, 2:1, 2.5:1, and 3:1). The formulated NPs were then dehydrated using different approaches that included spray-drying (SD), freeze-drying (FD), and spray-freeze drying (SFD) and used varying mannitol concentrations (0, 1:1, and 5:1 of total weight). The mannitol was served as a cryoprotectant in this study. Results: The best formulation achieved used a pH 5.5 with a mixing chitosan–ACE-2 ratio of 2:1, where ACE-2-loaded NPs had an average particle size of 303.7 nm, polydispersity index (PDI) of 0.21, encapsulation efficiency (EE) of 98.4%, and ACE-2 loading content (LC) of 28.4%. After reconstitution, all SD samples had a relatively low yield rate, but the ACE-2 NPs dehydrated specifically using SFD required a lower amount of added mannitol (1:1 of its total weight) and produced a higher yield rate (p < 0.05) and similar PDI and EE values, along with relatively good particle size and LC. This formulation also produced a high ACE-2 release and uptake in differentiated Caco-2 cells, thus representing an effective ACE-2 encapsulation procedure for use with dry powders. Conclusions: This work showed that spray-freeze drying was the best method to dehydrate ACE-2 NPs, using less cryoprotectant to create a significant advantage in terms of greater loading capacity with lower additive requirements.