Oral Administration Of Drug Research Articles

Systemic Statin Use and Pulp Chamber Calcification: A Pilot Retrospective Case Control Study Using Cone-Beam Computed Tomography.

This pilot retrospective case-control study questioned whether systemic statin use causes pulp calcification using cone-beam computed tomography images from the patients prescribed oral statins and comparing those of healthy individuals. CBCT scans of 54 patients, including 27 age- and sex-matched patients for the study and control groups, were analysed using Mimics Innovation Suite software. The study included patients using statins regularly for at least 1 year. Only intact teeth with opposing teeth were selected for the study group and matched with the control group. Dental crown and pulp chamber volumes were calculated and proportioned. The data were analysed with chi-square and Shapiro-Wilk tests to assess normal distribution, followed by Mann-Whitney U test if necessary. Statistical analysis showed no difference between the study and control groups (p = 0.505). Statin use duration did not cause statistically significant difference in terms of the reduction of pulp chamber volume (p = 0.141). Within the limitations of the study, systemic statin use did not cause dental pulp calcification. The results suggest, oral administration of the statin drugs is not an unfavourable condition for dental practice. Further studies with larger numbers of patients are needed to support this conclusion.

New Drug Delivery Systems for Stable Oral Absorption: Theory, Strategies, and Applications.

The oral dosage route still remains the most common and preferred route for drug administration due to convenient handling, high patient compliance, and cost-effectiveness. However, the oral absorption of drugs can be a complex process depending upon: (i) physicochemical properties of the drug (e.g., pKa, lipophilicity, solubility), (ii) pharmaceutical factors (e.g., dosage form), and (iii) physiological factors (e.g., gastrointestinal pH values, gastric emptying rate, gastric and intestinal pH, metabolism). Oral administration of drugs sometimes leads to poor and/or variable oral bioavailability, possible leading to unstable clinical outcomes. To offer stable and improved pharmacokinetic behavior of drugs, a number of formulation approaches have been developed with a focus on enhancement of the solubility, dissolution rate, and oral bioavailability of drugs. To provide new formulation platforms for better and safe medication, it is considered essential to understand the physicochemical, biochemical, metabolic, and biological barriers which limit overall drug bioavailability in more detail. The review article considers several crucial factors affecting oral absorption of drug substances. This article also describes the recent progress in formulation approaches to achieve stable and improved biopharmaceutical properties of orally-taken drugs.

Oral administration of herbal oligonucleotide drug JGL-sRNA-h7 ameliorates hyperglycemia in db/db mice and beagle dogs.

Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL-sRNA-h7 (B34735529, F1439.L002444.A11), could exhibit potent hypoglycemic effects by targeting glucose-6-phosphatase. Oral administration of sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes ameliorated hyperglycemia and diabetic kidney injury better than metformin in db/db mice. Furthermore, glucose tolerance was also improved in sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes-treated beagle dogs. Our study indicates that JGL-sRNA-h7 could be a promising hypoglycemic oligonucleotide drug.

Various drugs used in oral disintegration tablet formulation

Oral drug administration is more widely accepted because it is used to provide between 50 and 60 percent of medications. The solid dosage forms are commonly utilized since they are simple to administer, precise in their dosage forms, beneficial for self-medication, and preventive of discomfort, and last but not least, the excellent level of patient adherence. The capsules and tablets are the most widely used solid dose form administered orally. Aside from ingesting it does not possess any noteworthy drawbacks. Water plays a crucial function in this swallowing process. Even following this, some people had difficulty swallowing. In order to prevent these issues, mouth dissolving tablets were developed. They have the benefit of not requiring water and don't require swallowing because they dissolve or disintegrate in saliva. In light of the design it began to behave in two ways: first, some tablets disintegrated quickly, taking just a few moments in saliva. Another kind of tablet is known as a "first disintegration tablet" since it contains some substances that slowed down the tablet's rate of breakdown. Review attention was drawn to the concise talk about mouth dissolving tablets and the most recent versions available.

Costs of Potential Medication Wastage Due to Switching Treatment Among People With Multiple Sclerosis

Background: Unused medications negatively impact healthcare resource utilization and environmental safety, contribute substantially to annual healthcare expenditures, and may ultimately affect patient health outcomes. People with multiple sclerosis (PwMS) commonly switch disease-modifying therapies (DMTs), leading to medication wastage and substantial costs for insurers and patients. Objectives: To estimate the cost associated with potential medication wastage (PMW) in a subcohort of PwMS receiving oral or self-injectable US Food and Drug Administration–approved DMTs who switched DMTs in a calendar year in the United States. Methods: This retrospective cohort study included adults with MS and used PharMetrics® Plus claims data from 2017 to 2021. PwMS were required to have 12 months of continuous eligibility for the entire year and a claim for at least 2 unique DMTs during the same calendar year. The PMW cohort was defined as those who had an aggregate overlap in days’ supply across DMT switches within the year; those in the non-PMW cohort did not. The cost of PMW for insurers and PwMS due to overlap was calculated only at the point of switch to the new DMT and defined as the cost of the remaining days’ supply of the prior DMT. Results: The number of PwMS meeting the inclusion criteria was 1762 in 2017, 1947 in 2018, 1679 in 2019, 1461 in 2020, and 1782 in 2021. Approximately 95% of PwMS switched DMTs once within single calendar years, and 25% (n = 381-464) contributed to PMW. For those who had overlapping DMT supply, it was estimated that 34% to 38% of the DMT being switched from was potentially wasted. The total cost of PMW paid by the insurer and PwMS ranged from $1 200 866 to $1 489 859. While most of the total cost ($1 172 140-$1 450 328) was paid by the insurer, PwMS still owed substantial amounts ($28 726-$74 578). Across all PwMS, the per person per year cost ranged from $716 to $846. The estimated wastage and associated costs were consistent across all study years. Conclusions: DMT switching is common among PwMS, resulting in PMW and high costs to patients and insurers.

The triple combination DBDx alleviates cytokine storm and related lung injury

Cytokine storm is a life-threatening disorder, and therapeutic treatments are urgently needed. Here, we investigated the anti-cytokine storm efficacy of DBDx, a triple drug combination composed of dipyridamole, ubenimex and dexamethasone. Evaluated by lipopolysaccharide (LPS)-induced cytokine storm murine model, DBDx significantly improved survival rate and prolonged survival time of the model mice. Notably, the efficacy of DBDx was higher than that of dipyridamole, ubenimex and dexamethasone. Determined by ELISA, DBDx significantly reduced the LPS-stimulated serum levels of TNF-α, IL-6 and IL-1β in mice. Luminex assay showed that DBDx suppressed the serum levels of a wide variety of inflammatory cytokines and chemokines, which was more potent than dexamethasone alone. Otherwise, DBDx exerted similar inhibitory effects on cytokine profiles in bronchoalveolar lavage fluid. Histopathological observation showed that DBDx significantly reduced the LPS-induced thickening of alveolar septum, indicating its suppression of capillary congestion, edema and neutrophil infiltration in the lung. Ultra-structure analysis showed that DBDx suppressed the LPS-induced morphological changes of microvilli in type II pneumocytes. In vitro experiment showed that DBDx inhibited IL-6 and TNF-α secretion in THP-1 cells, and downregulated TLR4/NF-κB/HIF-1α signaling pathway. All of these results demonstrate that DBDx, a triple combination of clinical orally-administered drugs, can alleviate cytokine storm and related lung injury. DBDx is beneficial for treating cytokine storm disorders.

Coordinating expensive, difficult-to-obtain prophylactic medications before discharge: A quality improvement project in an academic stem cell transplant unit.

337 Background: Infections are a significant source of morbidity/mortality in allogeneic stem cell transplant (alloSCT) patients and antimicrobial prophylaxis has reduced deaths. Between July 2022 and July 2023, 21% of new alloSCT recipients were discharged from UVA Medical Center without posaconazole or isavuconazonium +/- letermovir in-hand at the time of hospital discharge necessitating daily oral drug administration at the infusion center until medication could be obtained. This led to excess cost for UVA, burden on clinic staff, missed doses, and patient frustration. We sought to decrease the number of new alloSCT recipients discharged without appropriate prophylaxis in-hand from 21% to 10% by November 2024. Methods: Per the 2023 ASCO Quality Training Program associated with this project, a Model for Improvement and Plan Do Study Act (PDSA) methodology was utilized. The population included alloSCT patients with new prescriptions (Rxs) for posaconazole or isavuconazonium +/- letermovir. The outcome measure was percentage of newly discharged alloSCT patients requiring oral prophylaxis at the infusion center. The process measure was Time to Affordable Medication (TAM) defined as days from Rx prior-authorization (PA) request to paid claim with an affordable copay (defined as a copay the patient was able/willing to pay, including free drug approvals or assistance programs). The counter measure consisted of initiating the Rx PA process 10 days prior to planned admission via a discharge test Rx order set instead of waiting until admission. This standardized process allowed for clearer communication and more time for pharmacy technicians to process the Rx for PA, copays, free drug applications, and pharmacy logistics. Upon admission, the official Rx was released to the discharge pharmacy. If Rx shipment was required, this was set up the week prior to discharge. An I-chart (3-sigma) statistical process control (SPC) chart was used to assess the intervention. Results: The baseline TAM was assessed retrospectively in 22 Rxs over 3 months prior to intervention for a mean of 7.5 days. PDSA cycle 1 was implemented Nov. 2023. TAM for the first 35 Rxs was 4.3 days and the SPC upper control limit decreased from 26.3 days to 13.3 days demonstrating overall markedly decreased variation despite data from early 2024 having greater variability due to new insurance deductibles. Rxs requiring 10 or more days were due to free drug application processes. Importantly, no newly discharged alloSCT patients have required drug administration at the infusion center. Conclusions: PDSA #1 resulted in a decrease in TAM of 3.2 days, decreased variation in the process, and no patients discharged without drug in hand. Since we have already surpassed our aim, next steps include demonstrating sustainability of the process and a survey requesting feedback to identify balance measures.

Formulation of protein-loaded nanoparticles via freeze-drying.

Several nanotechnology-based formulation strategies have been reported for the oral administration of biological drugs. However, a prerequisite often overlooked in developing these formulations is their adaptation to a solid dosage form. This study aimed to incorporate a freeze-drying step, using either mannitol or sucrose laurate (SLAE), into the formulation of new insulin-zinc nanocomplexes to render them resistant to intestinal fluids while maintaining a high protein loading. The resulting freeze-dried insulin-zinc nanocomplexes exhibited physicochemical properties consistent with the target product profile, including a particle size of ∼ 100nm, a zeta potential close to neutrality (∼ -15 mV) and a high association efficiency (> 90%). Importantly, integrating the freeze-drying step in the formulation significantly improved the colloidal stability of the system and preserved the stability of the insulin molecules. Results from in vitro and in vivo studies indicated that the insulin activity remained fully retained throughout the entire formulation and freeze-drying processes. In brief, we present a novel protein formulation strategy that incorporates a critical freeze-drying step, resulting in a dry powder enabling efficient protein complexation with zinc and optimized for oral administration.

The combination of hydrogels and rutin-loaded black phosphorus nanosheets treats rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by inflammation, joint pain, and cartilage degradation. The fluctuating nature of RA often necessitates long-term oral administration of treatment drugs, which can unfortunately lead to adverse effects such as gastrointestinal discomfort and hepatic and renal dysfunction. Therefore, a percutaneous local delivery method for the release of inflammatory modulators in arthritic joints represents a promising therapeutic approach for RA. In this study, we have developed a unique and innovative therapeutic platform (named BP-Rut@Gel). This hydrogel was formulated by incorporating the drug Rutin (Rut) into Black phosphorus nanosheets (BP) and subsequently integrating them within a Hyaluronic Acid (HA) and Polyvinyl Alcohol (PVA) matrix to create a composite hydrogel. Notably, Secondly, photothermal therapy (PTT) under Near-Infrared Irradiation (NIR) and anti-inflammatory drugs synergistically worked together to efficiently quell inflammation and enhance therapeutic effectiveness. Additionally, toxicity experiments have revealed that our synthesized black phosphorus nanosheet composite hydrogel possesses excellent biocompatibility and significantly reduces the inflammatory response in RA joints. Given these remarkable properties, our BP-Rut@Gel hydrogel held significant promise and demonstrated immense clinical potential for the treatment of RA.

Enhancement of oral bioavailability of ibrutinib using a liposil nanohybrid delivery system.

Liposils, synthesized via the liposome templating method, offer a promising strategy for enhancing liposome stability by employing a silica coating. This study focuses on the development of nanocarriers utilizing silica-coated nanoliposomes for encapsulating the poorly water-soluble drug, ibrutinib. Ibrutinib-loaded nanoliposomes were meticulously formulated using the reverse-phase evaporation technique, serving as templates for silica coating, resulting in spherical liposils with an average size of approximately 240 nanometers. Comprehensive characterization of the liposil's physical and chemical properties was conducted using various analytical methods, including dynamic light scattering, transmission electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction analysis. Liposils demonstrated superior performance compared to ibrutinib-loaded nanoliposomes, showing sustained drug release profiles in simulated intestinal fluids and resistance to simulated gastric fluid, as confirmed by dissolution studies. Moreover, ibrutinib liposils exhibited a significant increase in half-life (4.08-fold) and notable improvement in bioavailability (3.12-fold) compared to ibrutinib suspensions, as determined by pharmacokinetic studies in rats. These findings underscore the potential of liposils as nanocarriers for orally delivering poorly water-soluble drugs, offering enhanced stability and controlled release profiles, thereby improving bioavailability prospects and therapeutic efficacy. This approach holds promise for addressing challenges associated with the oral administration of drugs with limited solubility, thereby advancing drug delivery technologies and clinical outcomes in pharmaceutical research and development.

Prediction of the drug intestinal absorption and drug-induced intestinal toxicity with the use of cultured human/animal crypt-derived intestinal stem cells

Prediction of intestinal drug absorption and drug-induced intestinal toxicity is critical for the development of orally-administered drugs. However, it is difficult to accurately predict these events because of large species differences and a lack of appropriate in vitro assay. Then, we proposed the use of human crypt-derived intestinal cells for the prediction of intestinal absorption and the risk of intestinal toxicity. 3D human intestinal spheroids were established from fresh surgical specimens of proximal jejunum and terminal ileum using the conditioned media containing Wnt3a, R-spondin 3, and noggin. To generate 2D monolayer, spheroids were enzymatically dissociated into single cells and plated onto Matrigel-precoated culture plates/inserts. We have confirmed the activities of typical drug-metabolizing enzymes and uptake/efflux transporters in human jejunal spheroid-derived differentiated cells. Intestinal availability (Fg) estimated from the apical-to-basal permeation clearance across the jejunal monolayer showed a good correlation with in vivo human Fg values for five CYP3A substrate drugs. As for the prediction of intestinal toxicity, we found that the degree of ATP decreases in intestinal spheroids incubated with different EGFR-TKIs varied greatly depending on the drugs and the rank order of the extent of ATP decrease corresponded with that of frequency of clinically-observed diarrhea. We also constructed enterochromaffin (EC) cell-rich spheroids and quantified serotonin release from EC cells upon exposure to drugs for the prediction of drug-induced nausea and vomiting. As a result, we found that the serotonin release was related to the high/low risk of nausea and vomiting of each ALK/ROS1 kinase inhibitors.

Cyclodextrin-Polymethylsilsesquioxane Combined System as a Perspective Iron Delivery System for Oral Administration.

Anemia is a global health problem that affects both adults and children, but treatment is hampered by serious side effects, primarily associated with the gastrointestinal tract with oral administration of drugs. In this study, we aimed to develop an oral form of iron compounds using polymethylsilsesquioxane hydrogels. To boost loading efficiency and prolong release, the iron compounds (FeCl3 and ferrous D-Gluconate) are incorporated into a guest-host complex with 2-hydroxypropyl-beta-cyclodextrin. We used PRXD, SEM, EDX mapping, and FTIR to investigate the complex formation, as well as the incorporation of such complexes into hydrogels. The optimal system underlines a combination of ferrous D-Gluconate and HPCD in a 1:1 molar ratio, embedded into a hydrogel with a modest quantity of silicate crosslinks. We demonstrated the slowing of iron release in a gastric media. Mathematical investigation revealed that the Higuchi mechanism releases iron from the hydrogel.

Novel Drp1 GTPase Inhibitor, Drpitor1a: Efficacy in Pulmonary Hypertension.

Drp1 (dynamin-related protein 1), a large GTPase, mediates the increased mitochondrial fission, which contributes to hyperproliferation of pulmonary artery smooth muscle cells in pulmonary arterial hypertension (PAH). We developed a potent Drp1 GTPase inhibitor, Drpitor1a, but its specificity, pharmacokinetics, and efficacy in PAH are unknown. Drpitor1a's ability to inhibit recombinant and endogenous Drp1 GTPase was assessed. Drpitor1a's effects on fission were studied in control and PAH human pulmonary artery smooth muscle cells (hPASMC) and blood outgrowth endothelial cells (BOEC). Cell proliferation and apoptosis were studied in hPASMC. Pharmacokinetics and tissue concentrations were measured following intravenous and oral drug administration. Drpitor1a's efficacy in regressing monocrotaline-PAH was assessed in rats. In a pilot study, Drpitor1a reduced PA remodeling only in females. Subsequently, we compared Drpitor1a to vehicles in control and monocrotaline-PAH females. Drp1 GTPase activity was increased in PAH hPASMC. Drpitor1a inhibited the GTPase activity of recombinant and endogenous Drp1 and reversed the increased fission, seen in PAH hPASMC and PAH BOEC. Drpitor1a inhibited proliferation and induced apoptosis in PAH hPASMC without affecting electron transport chain activity, respiration, fission/fusion mediator expression, or mitochondrial Drp1 translocation. Drpitor1a did not inhibit proliferation or alter mitochondrial dynamics in normal hPASMC. Drpitor1a regressed monocrotaline-PAH without systemic vascular effects or toxicity. Drpitor1a is a specific Drp1 GTPase inhibitor that reduces mitochondrial fission in PAH hPASMC and PAH BOEC. Drpitor1a reduces proliferation and induces apoptosis in PAH hPASMC and regresses monocrotaline-PAH. Drp1 is a therapeutic target in PAH, and Drpitor1a is a potential therapy with an interesting therapeutic sexual dimorphism.

Lipid polymer hybrid nanoparticles against lung cancer and their application as inhalable formulation.

Lung cancer is a leading cause of global cancer mortality, often treated with chemotherapeutic agents. However, conventional approaches such as oral or intravenous administration of drugs yield low bioavailability and adverse effects. Nanotechnology has unlocked new gateways for delivering medicine to their target sites. Lipid-polymer hybrid nanoparticles (LPHNPs) are one of the nano-scaled delivery platforms that have been studied to exploit advantages of liposomes and polymers, enhancing stability, drug loading, biocompatibility and controlled release. Pulmonary administration of drug-loaded LPHNPs enables direct lung deposition, rapid onset of action and heightened efficacy at low doses of drugs. In this manuscript, we will review the potential of LPHNPs in management of lung cancer through pulmonary administration.

Inhibition of Giardia duodenalis by isocryptolepine -triazole adducts and derivatives

Giardia duodenalis, a widespread parasitic flagellate protozoan causing giardiasis, affects millions annually, particularly impacting children and travellers. With no effective vaccine available, treatment primarily relies on the oral administration of drugs targeting trophozoites in the small intestine. However, existing medications pose challenges due to side effects and drug resistance, necessitating the exploration of novel therapeutic options. Isocryptolepine, derived from Cryptolepis sanguinolenta, has demonstrated promising antimicrobial and anticancer properties. This study evaluated eighteen isocryptolepine-triazole adducts for their antigiardial activities and cytotoxicity, with ISO2 demonstrating potent antigiardial activity and minimal cytotoxicity on human intestinal cells. Metabolomics analysis revealed significant alterations in G. duodenalis metabolism upon ISO2 treatment, particularly affecting phospholipid metabolism. Notably, the upregulation of phytosphingosine and triglycerides, and downregulation of certain fatty acids, suggest a profound impact on membrane composition and integrity, potentially contributing to the parasite's demise. Pathway analysis highlighted glycerophospholipid metabolism, cytochrome b5 family heme/steroid binding domain, and P-type ATPase mechanisms as critical pathways affected by ISO2 treatment, underscoring its importance as a potential target for antigiardial therapy. These findings shed light on the mode of action of ISO2 against G. duodenalis and provide valuable insights for further drug development. Moreover, the study also offers a promising avenue for the exploration of isocryptolepine derivatives as novel therapeutic agents for giardiasis, addressing the urgent need for more effective and safer treatment options.

Novel Approaches for the Enhancement of Bioavailability of Drugs: An Updated Review.

In medicine, bioavailability is the percentage of a drug that enters the bloodstream and can be used to treat a patient. It has proven challenging throughout time to develop techniques that allow oral administration of most drugs, regardless of their properties, to achieve therapeutic systemic availability. This will be an impressive feat, considering that over 90% of pharmaceuticals are known to have limitations on their oral bioavailability. Improving bioavailability is crucial for optimizing the efficacy and safety of drugs. This review covers a wide range of techniques, including physical, chemical, and formulation approaches, highlighting their mechanisms, advantages, and limitations. Inhibitions of efflux pumps, inhibition of presystemic metabolism, and innovative drug delivery systems that capitalize on the gastrointestinal regionality of medicines are some of the new techniques that have drawn increased interest. Nanotechnology in pharmaceuticals is also being used in this field. We have collected the literature data from 2009 to 2024 using Science Direct, PubMed/Medline, Scopus, and Google Scholar.

Milk Exosome-Liposome Hybrid Vesicles with Self-Adapting Surface Properties Overcome the Sequential Absorption Barriers for Oral Delivery of Peptides.

Milk exosomes (mExos) have demonstrated significant promise as vehicles for the oral administration of protein and peptide drugs owing to their superior capacity to traverse epithelial barriers. Nevertheless, certain challenges persist due to their intrinsic characteristics, including suboptimal drug loading efficiency, inadequate mucus penetration capability, and susceptibility to membrane protein loss. Herein, a hybrid vesicle with self-adaptive surface properties (mExos@DSPE-Hyd-PMPC) was designed by fusing functionalized liposomes with natural mExos, aiming to overcome the limitations associated with mExos and unlock their full potential in oral peptide delivery. The surface property transformation of mExos@DSPE-Hyd-PMPC was achieved by introducing a pH-sensitive hydrazone bond between the highly hydrophilic zwitterionic polymer and the phospholipids, utilizing the pH microenvironment on the jejunum surface. In comparison to natural mExos, hybrid vesicles exhibited a 2.4-fold enhancement in the encapsulation efficiency of the semaglutide (SET). The hydrophilic and neutrally charged surfaces of mExos@DSPE-Hyd-PMPC in the jejunal lumen exhibited improved preservation of membrane proteins and efficient traversal of the mucus barrier. Upon reaching the surface of jejunal epithelial cells, the highly retained membrane proteins and positively charged surfaces of the hybrid vesicle efficiently overcame the apical barrier, the intracellular transport barrier, and the basolateral exocytosis barrier. The self-adaptive surface properties of the hybrid vesicle resulted in an oral bioavailability of 8.7% and notably enhanced the pharmacological therapeutic effects. This study successfully addresses some limitations of natural mExos and holds promise for overcoming the sequential absorption barriers associated with the oral delivery of peptides.

Enzyme/ROS dual-sensitive nanoplatform with on-demand Celastrol release capacity for enhanced ulcerative colitis therapy by ROS scavenging, microbiota rebalancing, inflammation alleviating

BackgroundThe oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release.MethodsA multiple sensitive nano-delivery system comprising β-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC.ResultsOwing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome.ConclusionsWe provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand.Graphical

Unlocking the potential of microfold cells for enhanced permeation of nanocarriers in oral drug delivery

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.

Nanocellulose-alginate composite beads for improving Ciprofloxacin bioavailability

Nanocellulose is a potential material utilized in numerous biomedical applications. However, its hydrophilic characteristic and uncontrolled encapsulated drug release hinders nanocellulose uses in oral drug administration. Thus, this work developed novel nanocellulose/alginate composite (CNC/Alg) beads for oral delivery and bioavailability enhancement of a model drug, Ciprofloxacin (CIP). CNC was green synthesized employing electrolysis process from sugarcane bagasse. CNC/Alg beads were formulated by dropwise adding CNC-Alg mixture in CaCl2 solution at room temperature. CIP was incorporated into CNC/Alg beads by adsorption technique. X-ray diffractometry and Fourier-transform infrared spectra images showed that the beads were effectively produced with high crystallinity of 75.5 %, and the typical bond of cellulose and alginate. Within 4 h of adsorption, CIP loading efficiency reached 45.27 %, with 87.2 % molecules in the zwitterionic state. The adsorption followed Elovich and pseudo-second-order models, indicating a multi-mechanism including both physical and chemical adsorptions. Importantly, in gastrointestinal tract, the beads could protect CIP from acidic stomach environment while releasing it sustainably in simulated intestinal condition (75.05 %). The beads also showed strong antibacterial activity against both Gram(−) and Gram(+) bacteria, as evidenced by low IC50 and minimum inhibitory concentration values. Finally, CNC/Alg beads could improve CIP bioavailability for effective oral drug delivery route.