OBJECTIVE: To evaluate the impact of the surface decoration of cannabidiol (CBD) loaded self-emulsifying drug delivery systems (SEDDS) on the efficacy of the formulations to cross the various barriers faced by orally administered drugs.
METHODS: Polyethylene glycol (PEG)-free polyglycerol (PG)-based SEDDS, mixed zwitterionic phosphatidyl choline (PC)/PEG-containing SEDDS and PEG-based SEDDS were compared regarding stability against lipid degrading enzymes, surface properties, permeation across porcine mucus, cellular uptake and cytocompatibility.
RESULTS: SEDDS with a size of about 200 nm with narrow size distributions were developed and loaded with 20-21 % of CBD. For PG containing PEG-free SEDDS increased degradation by lipid degrading enzymes was observed compared to PEG-containing formulations. The surface hydrophobicity of placebo SEDDS increased in the order of PG-based to mixed PC/PEG-based to PEG-based SEDDS. The influence of this surface hydrophobicity was also observed on the ability of the SEDDS to cross the mucus gel layer where highest mucus permeation was achieved for most hydrophobic PEG-based SEDDS. Highest cellular internalization was observed for PEG-based Lumogen Yellow (LY) loaded SEDDS with 92 % in Caco-2 cells compared to only 30 % for mixed PC/PEG-based SEDDS and 1 % for PG-based SEDDS, leading to a 100-fold improvement in cellular uptake for SEDDS having highest surface hydrophobicity. For cytocompatibility all developed placebo SEDDS showed similar results with a cell survival of above 75 % for concentrations below 0.05 % on Caco-2 cells.
CONCLUSIONS: Higher surface hydrophobicity of SEDDS to orally deliver lipophilic drugs as CBD seems to be a promising approach to increase the intracellular drug concentration by an enhanced permeation through the mucus layer and cellular internalization.

UNASSIGNED: Oral delivery of small interfering RNAs (siRNAs) draws significant attention, but the gastrointestinal tract (GIT) has many biological barriers that limit the drugs\' bioavailability. The aim of this work was to investigate the potential of nano- and micron-sized CaCO3 and PLA carriers for oral delivery of siRNA and reveal a relationship between the physicochemical features of these carriers and their biodistribution.
UNASSIGNED: In vitro stability of carriers was investigated in simulated gastric and intestinal fluids. Toxicity and cellular uptake were investigated on Caco-2 cells. The biodistribution profiles of the developed CaCO3 and PLA carriers were examined using different visualization methods, including SPECT, fluorescence imaging, radiometry, and histological analysis. The delivery efficiency of siRNA loaded carriers was investigated both in vitro and in vivo.
UNASSIGNED: Micro-sized carriers were accumulated in the stomach and later localized in the colon tissues. The nanoscale particles (100-250 nm) were distributed in the colon tissues. nPLA was also detected in small intestine. The developed carriers can prevent siRNA from premature degradation in GIT media.
UNASSIGNED: Our results reveal how the physicochemical properties of the particles, including their size and material type can affect their biodistribution profile and oral delivery of siRNA.

The convergence of polymer and pharmaceutical sciences has advanced drug delivery systems significantly. Carbohydrate polymers, especially carboxymethylated ones, offer versatile benefits for pharmaceuticals. Interpenetrating polymer networks (IPNs) combine synthetic and natural polymers to enhance drug delivery. The study aims to develop IPN beads using sodium carboxymethyl cellulose (SCMC) and carboxymethyl konjac glucomannan (CMKGM) for controlled release of ibuprofen (IB) after oral administration. Objectives include formulation optimization, characterization of physicochemical properties, evaluation of pH-dependent swelling and drug release behaviors to advance biocompatible and efficient oral drug delivery systems. The beads were analyzed using SEM, FTIR, DSC, and XRD techniques. Different ratio of polymers (CMKGM:SCMS) and crosslinker concentrations (2&4 %w/v) were used, significantly impacting bead size, swelling, drug encapsulation, and release characteristics. DSC results indicated higher thermal stability in IPN beads compared to native polymers. XRD revealed IB dispersion within the polymer matrix. IPN beads size ranged from 580 ± 0.56 to 324 ± 0.27 μm, with a nearly spherical shape. IPN beads exhibited continuous release in alkaline conditions (pH 7.4) and minimal release in acidic media (pH 1.2). These findings suggest that the formulated IPN beads can modulate drug release in both acidic and alkaline environments, potentially mitigating the gastric adverse effects often associated with oral administration of IB.

UNASSIGNED: Rani Therapeutics is developing a robotic pill (RP), an oral drug delivery platform called RaniPill™ that can deliver a number of biotherapeutics with high bioavailability; eliminating the need for injections. While patients in general prefer oral to injectable therapies, preference for a more frequent oral regimen compared to a less frequent injectable regimen is unknown. Two marketing surveys were conducted to gather data on preference for oral versus injectable therapies. A clinical study gathered data on participant preference for oral pills vs injections before and after swallowing a Mock-RP capsule.
UNASSIGNED: A total of 1689 adults taking injections (mean duration 3-7 years) to treat endocrine or inflammatory conditions were anonymously surveyed online for their preference to administer/prescribe medications orally via the RP. In the clinical study, 150 participants currently taking injections for chronic conditions evaluated the swallowability of a Mock-RP and completed a questionnaire regarding their preferences.
UNASSIGNED: Majority of respondents surveyed stated they would be willing to convert to an oral alternative over their current parenteral therapy regardless of drug or disease. In the clinical study, all participants were able to swallow the Mock-RP and 91% indicated their preference for the oral route versus their current parenteral route of drug administration. Survey respondents and those in the clinical study using frequent injections were more willing to select a once-daily capsule compared to those injecting infrequently. Even study participants who inject infrequently (≥monthly: 80%) would prefer a once-daily pill over their injection regimen.
UNASSIGNED: Patients taking injections and prescribing physicians strongly prefer oral dosing to parenteral administration of biologics even if dosing frequency with the oral option, such as the RP, is increased.

The aim of this study was to assess the effectiveness of neroli-flavored chewing gum in reducing anxiety. A single-blind, two-group study was conducted on 72 university students. Participants were randomly assigned to either the commercial neroli-flavored chewing gum (CNC) group or the natural hydro-distilled neroli-flavored chewing gum (NNC) group. The research instrument used was Spielberger\'s State-Anxiety questionnaire. While there was no significant difference in anxiety scores between the CNC and NNC groups before the intervention, a significant difference was observed in anxiety scores 20 min after the intervention. Within-group comparisons indicated statistically significant differences between pre-test and post-test values of anxiety in the NNC group. The results of this study suggest that natural hydro-distilled neroli-flavored chewing gum can reduce anxiety in university students.

The therapeutic effects of orally administered nanocarriers depend on their ability to effectively permeate the intestinal mucosa, which is one of the major challenges in oral drug delivery. Microfold cells are specialized enterocytes in the intestinal epithelium known for their high transcytosis abilities. This study aimed to compare and evaluate two targeting approaches using surface modifications of polymer-based nanocarriers, whereas one generally addresses enterocytes, and one is directed explicitly to microfold cells via targeting the sialyl LewisA motif on their surface. We characterized the resulting carriers in terms of size and charge, supplemented by scanning electron microscopy to confirm their structural properties. For predictive biological testing and to assess the intended targeting effect, we implemented two human intestinal in vitro models containing microfold-like cells. Both models were thoroughly characterized prior to permeation studies with the different nanocarriers. Our results demonstrated improved transport for both targeted formulations compared to undecorated carriers in the in vitro models. Notably, there was an enhanced uptake in the presence of microfold-like cells, particularly for the nanocarriers directed by the anti-sialyl LewisA antibody. These findings highlight the potential of microfold cell targeting to improve oral administration of drugs and emphasize the importance of using suitable and well-characterized in vitro models for testing novel drug delivery strategies.

Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids extracted from Sulfolobus acidocaldarius. The primary aim of this study was to investigate the exceptional stability of archaeosomes as potential carriers for oral drug delivery, with a focus on powdered formulations. The archaeosomes were negatively charged with a size of approximately 100 nm and a low polydispersity index. To assess their suitability for oral delivery, the archaeosomes were loaded with two model drugs: calcein, a fluorescent compound, and insulin, a peptide hormone. The archaeosomes demonstrated high stability in simulated intestinal fluids, with only 5% of the encapsulated compounds being released after 24 h, regardless of the presence of degrading enzymes or extremely acidic pH values such as those found in the stomach. In a co-culture cell model system mimicking the intestinal barrier, the archaeosomes showed strong adhesion to the cell membranes, facilitating a slow release of contents. The archaeosomes were loaded with insulin in a single-step procedure achieving an encapsulation efficiency of approximately 35%. These particles have been exposed to extreme manufacturing temperatures during freeze-drying and spray-drying processes, demonstrating remarkable resilience under these harsh conditions. The fabrication of stable dry powder formulations of archaeosomes represents a promising advancement toward the development of solid dosage forms for oral delivery of biological drugs.

Amorphous solid dispersion (ASD) has been widely used to enhance the oral bioavailability of water-insoluble drugs for oral delivery because of its advantages of enhancing solubility and dissolution rate. However, the problems related to drug recrystallization after drug dissolution in media or body fluid have constrained its application. Recently, a self-nanomicellizing solid dispersion (SNMSD) has been developed by incorporating self-micellizing polymers as carriers to settle the problems, markedly improving the ability of supersaturation maintenance and enhancing the oral bioavailability of drug. Spontaneous formation and stability of the self-nanomicelle (SNM) have been proved to be the key to supersaturation maintenance of SNMSD system. This offers a novel research direction for maintaining supersaturation and enhancing the bioavailability of ASDs. To delve into the advantages of SNMSDs, we provide a concise review introducing the formation mechanism, characterization methods and stability of SNMs, emphasizing the advantages of SNMSDs for oral drug delivery facilitated by SNM formation, and discussing relevant research prospects.

The self-assembling aggregated structures of natural products have gained significant interest due to their simple synthesis, lack of carrier-related toxicity, and excellent biological efficacy. However, the mechanisms of their assembly and their ability to traverse the gastrointestinal (GI) barrier remain unclear. This review summarizes various intermolecular non-covalent interactions and aggregated structures, drawing on research indexed in Web of Science from 2010 to 2024. Cheminformatics analysis of the self-assembly behaviors of natural small molecules and their supramolecular aggregates reveals assembly-favorable conditions, aiding drug formulation. Additionally, the review explores the self-assembly properties of macromolecules like polysaccharides, proteins, and exosomes, highlighting their role in drug delivery. Strategies to overcome gastrointestinal barriers and enhance drug bioavailability are also discussed. This work underscores the potential of natural products in oral drug delivery and offers insights for designing more effective drug delivery systems.

BACKGROUND: Type I interferons (IFN-I)-a group of cytokines with immunomodulatory, antiproliferative, and antiviral properties-are widely used as therapeutics for various cancers and viral diseases. Since IFNs are proteins, they are highly susceptible to degradation by proteases and by hydrolysis in the strong acid environment of the stomach, and they are therefore administered parenterally. In this study, we examined whether the intestinal bacterium, enteropathogenic Escherichia coli (EPEC), can be exploited for oral delivery of IFN-Is. EPEC survives the harsh conditions of the stomach and, upon reaching the small intestine, expresses a type III secretion system (T3SS) that is used to translocate effector proteins across the bacterial envelope into the eukaryotic host cells.
RESULTS: In this study, we developed an attenuated EPEC strain that cannot colonize the host but can secrete functional human IFNα2 variant through the T3SS. We found that this bacteria-secreted IFN exhibited antiproliferative and antiviral activities similar to commercially available IFN.
CONCLUSIONS: These findings present a potential novel approach for the oral delivery of IFN via secreting bacteria.