First-pass Metabolism Research Articles

Intranasal Route an Alternative Approach for Systemic Drug Delivery: Recent Strategies and Progression

: Intranasal administration has proven to be a viable alternative for local and systemic delivery of varied therapeutic agents. This route has been potentially researched for delivering polar compounds, vaccines, hormones, peptides, proteins, etc. Being non-invasive and painless with a fast onset of action (both local and systemic), intranasal has become an ideal route for medication to children. This route is specifically employed for the delivery of drugs that are unstable in GIT, which gets significantly degraded or metabolized by the first-pass effect. The nasal route's high absorption and permeability profile has led to its exploration as a substitute for parenteral delivery. This paper reviews the feasibility and potentials of intranasal administration, discussing its benefits, drawbacks, market analysis, factors affecting nasal drug delivery system, conventional and novel strategies (polymeric and nano-carrier-based delivery systems) to improve nasal ab-sorption and its clinical management of varied systemic and topical disorders viz. neurodegenerative, pulmonary, microbial, neoplastic, etc.

Transdermal Drug Delivery System of Linagliptin Sustained-release Microparticle Gels: In vitro Characterization and In vivo Evaluation.

Linagliptin (LNG) exhibits poor bioavailability and numerous side effects, significantly limiting its use. Transdermal drug delivery systems (TDDS) offer a potential solution to overcome the first-pass effect and gastrointestinal reactions associated with oral formulations. The aim of this study was to develop LNG microparticle gels to enhance drug bioavailability and mitigate side effects. Linagliptin hyaluronic acid (LNG-HA) microparticles were prepared by spray drying method and their formulation was optimized via a one-factor method. The solubility and release were investigated using the slurry method. LNG-HA microparticle gels were prepared and optimised using in vitro transdermal permeation assay. The hypoglycaemic effect of the LNG-HA microparticle gel was examined on diabetic mice. The results indicated that the LNG-HA microparticle encapsulation rate was 84.46%. Carbomer was selected as the gel matrix for the microparticle gels. Compared to the oral API, the microparticle gel formulation demonstrated a distinct biphasic release pattern. In the first 30 minutes, only 43.56% of the drug was released, followed by a gradual release. This indicates that the formulation achieved a slow-release effect from a dual reservoir system. Furthermore, pharmacodynamic studies revealed a sustained hypoglycemic effect lasting for 48 hours with the LNG microparticle gel formulation. These findings signify that the LNG microparticle gel holds significant clinical value for providing sustained release and justifies its practical application.

Exploring peptide dendrimers for intestinal lymphatic targeting: formulation and evaluation of peptide dendrimer conjugated liposomes for enhancing the oral bioavailability of Asenapine maleate.

Asenapine maleate (ASPM) is a second-generation atypical antipsychotic that is approved for treating acute schizophrenia and bipolar disorder in adults by the US FDA. The major downside of ASPM therapy is rapid, extensive first-pass hepatic metabolism following its oral administration with a very low oral bioavailability of < 2%. In this work, we developed ASPM nanoformulations conjugated with ligands such as arginine-glycine-aspartic acid (RGD) and peptide dendrimers (PDs) with the intention of improving the oral bioavailability of the drug by targeting it to the intestinal lymphatic system (ILS). Peptide dendrimers (PDs), both lipidated and nonlipidated, were synthesized by Fmoc solid phase peptide synthesis (SPPS). Reverse phase high performance chromatography (RP-HPLC) was used to purify the synthesized PDs, and the PDs were characterized by differential scanning calorimetry (DSC) electrospray ionization mass spectroscopy (ESI+-MS), Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy. The thin film hydration method was used to prepare liposomes, and the process variables affecting the liposome parameters were optimized using the Box‒Behnken design (BBD).Liposomes were PEGylated using DSPE-PEG-COOH2000 and further conjugated with ligands (RGD, PD-1 and PD-2) using EDC-NHS chemistry. The formulation was characterized using different spectroscopic techniques. In vitro, cell line studies, such as cytotoxicity, cell uptake, uptake mechanism, and receptor saturation studies, were performed on both Caco2 and Raji-B cells. The pharmacokinetic parameters of the developed liposomal formulation were evaluated using pharmacokinetic studies on Sprague- Dawley (SD) rats. The psychostimulant-induced hyperactivity model was used to evaluate the pharmacodynamic performance of the developed formulations by measuring the reversal of hyperlocomotor activity induced by levodopa-carbidopa.

ENHANCING TRANSDERMAL DELIVERY OF POORLY WATER-SOLUBLE NSAIDS: EFFECTIVE STRATEGIES

Transdermal drug delivery offers significant advantages for administering non-steroidal anti-inflammatory drugs (NSAIDs) and anti-complementary drugs, particularly those with poor water solubility. This delivery route bypasses first-pass metabolism and gastrointestinal degradation, enhancing bioavailability and patient compliance. However, the stratum corneum, the outermost layer of the skin, poses a formidable barrier to drug permeation. To address this challenge, several innovative strategies have been developed to improve the transdermal delivery of these poorly soluble drugs. Chemical enhancers, such as alcohols, fatty acids, and surfactants, can disrupt the lipid structure of the stratum corneum, increasing drug solubility and permeability. Nanoformulations, including liposomes, niosomes, solid lipid nanoparticles, and nanoemulsions, enhance drug solubility, provide protection against degradation, and facilitate controlled release with deeper skin penetration. Prodrugs, designed to convert into the active drug within the skin, can improve solubility and permeability. Physical methods like microneedles, iontophoresis, and phonophoresis create micropores or use electrical and ultrasound waves to enhance permeation without compromising skin integrity. Cyclodextrins form inclusion complexes with drugs, boosting solubility and stability. Hydrogels and polymer-based formulations create a moist environment for sustained drug release and better absorption. Co-solvents and surfactants, such as ethanol and DMSO, further enhance solubility and disrupt the stratum corneum to facilitate drug penetration. Electroporation and thermal ablation transiently disrupt the skin barrier, significantly improving drug permeation. These strategies, individually or in combination, hold promise for optimizing the transdermal delivery of poorly water-soluble NSAIDs and anticomplementary drugs, ensuring effective therapeutic outcomes and improved patient compliance.

Advances in Transdermal Drug Delivery: The Development of Microneedle Technology for Improved Therapeutic Outcomes

Transdermal Drug Delivery Systems (TDDS) represent a significant advancement in therapeutic administration by allowing drugs to bypass the gastrointestinal system and first-pass hepatic metabolism, enhancing patient compliance, and enabling sustained drug release. However, traditional TDDS face limitations, including resistance from the skin's natural barrier and limited efficacy in delivering large or hydrophilic molecules. Microneedle (MN) technology offers a breakthrough solution, using minimally invasive micron-sized needles to bypass the stratum corneum, facilitating efficient drug delivery without significant pain or discomfort. This review explores the evolution and recent advancements in microneedle technology, highlighting its role in overcoming the limitations of conventional TDDS. Microneedles have been shown to enhance drug bioavailability, reduce side effects, and expand the range of deliverable therapeutics, including vaccines, insulin, and genetic materials. The development of bioinspired 4D microneedles further extends their application to diagnostics and cosmetic treatments, positioning MNs as a versatile tool in modern medicine. Key sections of the review focus on the types of microneedles—solid, coated, dissolving, hollow, and hydrogel-forming—and their respective fabrication methods, materials, and drug delivery mechanisms. The review also discusses the challenges related to scaling up production, ensuring consistent quality, and regulatory hurdles in achieving clinical approval. Future directions include the integration of microneedles with nanotechnology, combination therapies, and sustainable design, particularly in developing regions where biodegradable materials may address environmental and disposal concerns. The potential for microneedle technology to revolutionize transdermal drug delivery, diagnostics, and therapeutic monitoring is significant, with ongoing research paving the way for multifunctional applications that can reshape patient care and treatment modalities.

Direct Aspiration Versus Combined Technique for Anterior Distal, Medium Vessel Occlusions Stroke: The JET Distal Vessel Occlusion Study.

The optimal mechanical thrombectomy technique for distal, medium vessel occlusion (DMVO) stroke remains unknown. We aimed to compare the safety and efficacy of 2 thrombectomy first-line approaches, direct aspiration (DA), and combined technique (CT) in patients with DMVOs. We conducted a retrospective review of a prospectively collected multicenter database of patients with DMVOs (at or distal to M2 and A1), who underwent mechanical thrombectomy with JET D reperfusion catheters between January 2020 and December 2021. The primary end point was the rate of first-pass complete recanalization, defined as modified treatment in cerebral infarction (mTICI) 3. The hemorrhagic complications, the 90 days functional independence rate (modified Rankin Scale 0-2), and mortality were also evaluated. A total of 171 consecutive patients were enrolled (95 in DA and 76 in CT cohort). The 2 groups had comparable demographics and baseline characteristics. The DA group had a higher rate of first-pass effect (40.0% vs 10.5%, P < .001), final mTICI 2b-3 (89.5% vs 71.1%, P = .003) and final mTICI 3 (58.9% vs 28.9%, P < .001), shorter groin to reperfusion time (65 ± 43 min vs 101 ± 60 min, P < .001), and higher rate of 90-day functional independence (63.7% vs 36.1%; P = .001) compared with the CT group. There were no significant differences in hemorrhagic complications between the 2 groups. The DA group showed a lower rate of 90-day mortality (9.9% vs 27.8%; P = .004). In patients with DMVOs, DA with a distal dedicated reperfusion catheter appears to demonstrate better safety and efficacy when compared with the CT using the same catheter.

Association of Reperfusion and Procedural Characteristics with Endovascular Thrombectomy Outcomes in Large Core Stroke: Sub-Analysis from the SELECT2 Trial.

From the SELECT2 trial, we evaluated the association between reperfusion status, first-pass effect (near-complete or complete reperfusion [extended thrombolysis in cerebral infarction (eTICI) 2c-3] in 1 pass), procedure time and primary technique (aspiration vs stent-retriever) with functional outcomes in patients receiving EVT across ASPECTS (3 vs 4 vs 5) and core estimate strata (<70 vs ≥70ml, <100 vs ≥100ml, and <150 vs ≥150ml). Of 180 patients who received thrombectomy, 144 (80%) achieved successful reperfusion (eTICI 2b-3) and demonstrated better clinical outcomes (adjusted generalized odds ratios [aGenOR]: 1.48, 95% confidence interval [CI]: 1.01-2.15), compared with unsuccessful reperfusion. Results were consistent across ASPECTS and core estimate strata. Additionally, complete or near-complete reperfusion (eTICI 2c-3) was associated with better functional outcome (aGenOR: 1.99, 95% CI: 1.33-2.97) in patients achieving successful reperfusion. Functional outcome point estimates favored those with first-pass-effect (42 of 167 (25%), aGenOR: 1.46, 95% CI: 0.96-2.24). Longer procedure time was associated with worse modified Rankin scale (mRS) distribution (aGenOR: 0.92, 95% CI: 0.87-0.96, p-value = 0.001 for 10 minutes increment). Aspiration-first technique was used in 43 of 154 (25%) patients and was not associated with higher reperfusion (88% vs 78%, p = 0.18) or better functional outcome (aGenOR: 0.74, 95% CI: 0.50-1.10) as compared with stent-retriever first. Successful reperfusion resulted in improved clinical outcomes in large core patients across baseline ischemic core strata. Near complete or complete reperfusion was further associated with better outcomes, whereas prolonged procedures were associated with worse outcomes. Results were consistent regardless of the technique used. ANN NEUROL 2024.

Transport functions of intestinal lymphatic vessels.

Lymphatic vessels are crucial for fluid absorption and the transport of peripheral immune cells to lymph nodes. However, in the small intestine, the lymphatic fluid is rich in diet-derived lipids incorporated into chylomicrons and gut-specific immune cells. Thus, intestinal lymphatic vessels have evolved to handle these unique cargoes and are critical for systemic dietary lipid delivery and metabolism. This Review covers mechanisms of lipid absorption from epithelial cells to the lymphatics as well as unique features of the gut microenvironment that affect these functions. Moreover, we discuss details of the intestinal lymphatics in gut immune cell trafficking and insights into the role of inter-organ communication. Lastly, we highlight the particularities of fat absorption that can be harnessed for efficient lipid-soluble drug distribution for novel therapies, including the ability of chylomicron-associated drugs to bypass first-pass liver metabolism for systemic delivery. In all, this Review will help to promote an understanding of intestinal lymphatic-systemicinteractionsto guide future research directions.

Synthesis and characterization of 2-(3,4-dihydroxyphenyl)-4-((4-hydroxyphenyl)imino)-4h-chromene-3,5,7-triol: In vitro biological evaluation and computational analysis

Secondary phenolic metabolites like flavonoids, that are found in numerous plant sections and have a range of uses. Quercetin falls under the category of flavonols, belonging to the flavonoids found in various medicinal plants, some common fruits, and vegetables with various applications. However, quercetin, with its various applications, is not well established in the pharmaceutical industry since it is associated with a lot of drawbacks, like instability in the gastrointestinal tract, the first-pass effect, solubility issues, etc. Quercetin-Schiff base derivatives are essential for targeting cancer cells and enhancing biological activities due to the formation of the C=N (imine group), which plays a major role in enhancing biological activities. In this research article, quercetin Schiff base (Q1sb) was synthesised and analysed using spectroscopic techniques like 1H NMR, 13C NMR, HRMS, etc. Biological activities like anti-bacterial, antioxidant, anti-inflammatory, and cytotoxicity analyses were done on four cancer cell lines, namely A549, HeLa, HepG2, and MCF-7, and molecular docking were done on some of the common targets. The first section explains the characteristics of flavonoid, the therapeutic action and drawbacks of quercetin, and the importance of Schiff base derivatives; the second section explains the synthesis method and characterization; and the third section explains the biological applications and molecular docking studies.

Single-Center Experience With Endovascular Therapy in Acute Occlusion of ICAS: Preferred Stent Thrombectomy Versus Preferred Angioplasty.

The preferred endovascular therapy (EVT) for large-vessel occlusion in intracranial atherosclerosis (ICAS) is unknown. We compared the efficacy of preferred stent thrombectomy and preferred angioplasty in patients with acute large-vessel occlusion in ICAS. Data from consecutive EVT patients (May 2020 to September 2023) with acute middle cerebral artery occlusion in ICAS were retrospectively analyzed. Preferred angioplasty was performed if there was a preoperative "microcatheter first-pass effect;" otherwise, preferred stent thrombectomy was performed. Analyses were grouped according to the two EVT treatments. Clinical data of all patients, including the time from puncture to recanalization, rate of successful reperfusion, early neurological improvement, intracranial hemorrhage, and modified Rankin Scale score at 90 days, were recorded and analyzed. Six-two patients were enrolled in this study (mean age was 60.66±13.21y, 22.6% female). The preferred angioplasty group had a higher first-pass recanalization rate than the preferred stent thrombectomy group (61.3% vs. 21.9%, P <0.001) and a higher proportion of patients who were functionally independent (defined as a modified Rankin Scale score of 0 to 3) at 90 days [odds ratio,3.681; 95% confidence interval (CI):1.009 to 13.428; P =0.048]. There was no significant difference between the groups in the time from puncture to recanalization, the frequency of successful reperfusion, and early neurological improvement, or intracranial hemorrhage ( P >0.05). This study suggests that for acute middle cerebral artery occlusion in ICAS, preferred angioplasty may be a safe and effective procedure.

Fabrication of Self-powered Silicon Microneedles for Transdermal Drug Delivery

Abstract Transdermal drug delivery has been widely studied in recent years. Compared with other methods of drug delivery, this method has many advantages, such as convenient, improving patient compliance and avoiding first-pass effect. However, the low efficiency of this method needs to be overcome. In this paper, a micro-invasive transdermal drug delivery mechanism with synergic coupling of microneedle force field and triboelectric field is proposed, which can enhance the efficiency of transdermal drug delivery and is easy to operate and use. First, a silicon solid microneedle array was fabricated by micromachining technology, and its size parameters could be flexibly adjusted. Second, a metal layer with microstructure was fabricated on the back of the microneedle by sputtering technology as the positive friction layer of the triboelectric structure. Last, the microneedle and the triboelectric structure were combined into a single composite structure by using FPC wires. The experimental results showed that the transdermal amount increased with the increase of external excitation force, frequency and the number of microneedle arrays. Under the same conditions, the skin penetration of the two mechanisms combined was 3-8 times higher than that of the single use.

Advanced Technologies in Rectal Drug Delivery Systems: A Comprehensive Review of Recent Innovations and Future Prospects

Abstract: Rectal Drug Delivery System (RDDS) emerges as an alternative administration route due to the rectum's small surface area and limited enzyme activity, which contribute to efficient drug absorption. RDDS offers various advantages, such as reduced first-pass metabolism, rapid absorption of low molecular weight drugs, and the ability to accommodate large retention volumes and facilitate absorption via the lymphatic system. Moreover, RDDS is preferable for drugs with low stability, solubility, and permeability via oral administration, as well as effectively addressing concerns related to gastric irritation or degradation. This review delves into the factors influencing drug absorption in RDDS, including drug properties, formulation types, and physiological and pathology-associated considerations. It further explores conventional RDDS, including enemas, suppositories, tablets, gels, sprays, ointments, and creams, as well as novel approaches involving nanoparticles, liposomes, microspheres, and solid lipid nanoparticles (SLNs) in rectal dosage forms. Furthermore, the challenges and prospects of RDDS in treating rectal diseases are discussed. This review provides valuable insights into the potential of RDDS, highlighting the importance of continuous research and development in enhancing patient outcomes and advancing healthcare practices.

Development and evaluation of mucoadhesive buccal films for the sustained release of diclofenac sodium: An innovative approach for pain management

The research explores the development and evaluation of mucoadhesive buccal films for the sustained release of diclofenac sodium, a widely used non-steroidal anti-inflammatory drug (NSAID) for pain relief. Mucoadhesive buccal films are an innovative drug delivery system designed to adhere to the mucous membrane in the oral cavity, enabling the controlled release of drugs directly into the bloodstream, bypassing first-pass metabolism and improving therapeutic outcomes. These films provide sustained release, localized action, and improved compliance, making them more convenient for patients. Mucus membranes, which are moist surfaces lining body cavities, are the main components of mucus gels. The wetting theory applies to mucoadhesion, which involves the release of mucus from the mucosal surface into the bloodstream. The study aims to develop a more efficient and effective method for the controlled release of diclofenac sodium, a potent anti-inflammatory and analgesic drug.

Oral mucoadhesive drug delivery system: Formulation strategies and evaluation techniques

Mucoadhesive drug delivery systems (MDDS) represent an innovative method for administering drugs through oral routes such as the buccal, sublingual, and gingival areas. These systems leverage natural or synthetic polymers to ensure prolonged adherence to mucosal surfaces, enabling extended and controlled release of medication. Several factors influence the effectiveness of mucoadhesion, including the hydrophilicity of polymers, molecular weight, and environmental factors like pH and moisture levels. MDDS can take various forms, including tablets, films, patches, lozenges, and gels, each offering different drug release profiles such as immediate, sustained, or controlled. These systems enhance drug bioavailability by avoiding first-pass metabolism, making them particularly beneficial for medications with low oral bioavailability or those requiring targeted delivery. Although MDDS offer improved patient compliance and therapeutic effectiveness, they still face challenges like irritation, taste concerns, and the diluting effect of saliva, which can impact drug stability. Despite these challenges, MDDS hold significant promise for advancing drug delivery technologies across various medical applications. This review thoroughly examines the mechanisms, advantages, limitations, and future prospects of mucoadhesive drug delivery systems.

Circulating metabolites of Borneolum syntheticum (Bingpian) ameliorate atherosclerosis in ApoE-/- mice via inhibiting macrophage foam-cell formation.

Translational pharmacological research on traditional medicines lays the foundation for precisely understanding how the medicines function in the body to deliver therapeutic benefits. Borneolum syntheticum (Bingpian) is commonly used in Chinese herbal medicines for coronary heart disease, but its specific cardiovascular impact remains poorly understood. Isoborneol, a constituent of Bingpian, has been found to reduce lipid accumulation in macrophages in vitro, but its oral bioavailability is limited. This investigation aimed to evaluate anti-atherosclerotic effects of Bingpian, based on understanding its first-pass metabolism. Human subjects orally received an herbal medicine containing Bingpian and their plasma samples were analyzed to identify the major circulating compounds of Bingpian, with the metabolism that was also characterized in vitro and in mice. The identified compounds were evaluated for their ability to inhibit macrophage foam-cell formation induced by oxidized low-density lipoprotein. Furthermore, the anti-atherosclerotic effect of repeatedly dosed Bingpian was assessed in ApoE-/- mice fed a high-fat diet. In human subjects, the major circulating compounds of Bingpian were metabolites, rather than their precursor constituents borneol and isoborneol. These constituents were efficiently absorbed in the intestinal tract but underwent significant first-pass metabolism, involving UGT2B7-mediated glucuronidation into borneol-2-O-glucuronide and isoborneol-2-O-glucuronide, respectively, and CYP2A6/2B6/3A-mediated oxidation both into camphor. Despite their poor membrane permeability, hepatic efflux of borneol-2-O-glucuronide and isoborneol-2-O-glucuronide into the systemic circulation was enhanced by MRP3/4. The circulating metabolites, particularly their combinations, markedly inhibited macrophage foam-cell formation induced by oxidized low-density lipoprotein in vitro. Sub-chronic administration of Bingpian (30 mg·kg-1·d-1, i.g.) for 12 weeks significantly decreased atherosclerotic lesion size and enhanced plaque stability in ApoE-/- mice. Systemic exposure to Bingpian metabolites in mice closely resembles that in humans, suggesting that the pharmacodynamic effects of Bingpian in mice are likely applicable to humans. Overall, the cardiovascular benefits of Bingpian involve reducing atherosclerosis by inhibiting foam-cell formation through its metabolites. This investigation supports that oral Bingpian could be a druggable agent for reducing atherosclerosis.

Population pharmacokinetic and pharmacodynamic model of evogliptin: Severe uremia increases the bioavailability ofevogliptin.

Uremia, a condition characterized by the retention of uremic toxins due to impaired renal function, may affect drug metabolism mediated by CYP3A4 enzymes. Evogliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor diabetic drug that is primarily metabolized by CYP3A4. This study aimed to construct a population pharmacokinetic (PK) and pharmacodynamic (PD) model for evogliptin in patients with varying degrees of renal disease, including end-stage renal disease on hemodialysis. A total of 688 evogliptin concentration and 598 DPP-4 activity data were available from 46 subjects. PK and PD data analyses were performed using a nonlinear mixed-effects model. The PK of evogliptin was optimally described by a two-compartment model with first-order absorption. The significant covariates in the final model included blood amylase and triglyceride on F1 (relative bioavailability). The simulation findings, together with previously reported PK data, provided evidence of a significant inhibition of the first-pass effect of evogliptin in patients with renal impairment. A direct link sigmoidal Emax model was developed to describe the relationship between evogliptin concentration and DPP-4 inhibition. The PD model predicted significant inhibition of DPP-4 at maximum effect (Emax: 88.9%) and a low EC50 value (1.08 μg/L), indicating the high potency and efficacy of evogliptin. The developed PK/PD model accurately predicted exposure and the resulting DPP-4 activity of evogliptin in renal impairment. The findings of this study suggest that renal impairment and associated biochemical changes may impact the bioavailability of CYP3A4-metabolized drugs.

Deep eutectic solvent combined with permeation enhancer strategy to convert tandospirone from oral to transdermal formulations improving drug bioavailability

Tandospirone(Tan) is a commonly used drug for anxiety treatment. However, it has a significant first-pass effect and needs to be taken three times a day. To increase the bioavailability of the drug and reduce the number of administrations, this work amid to prepare a Tan patch that can be administered once a day by using the strategy of therapeutic deep eutectic solvent(THEDES) in cooperation with chemical permeation enhancer(CPE). In this study, four organic acids and five permeation enhancers were selected, and the optimized formulation was obtained by single-factor investigation and Box-Behnken design. The optimized formulation could significantly enhance drug loading by 2.5-fold and skin permeation up to 586.6 ± 17 μg/cm2 in rats. Based on pharmacokinetic results, compared to oral administration, the drug exhibited a substantially elevated bioavailability, registering a 17-fold increase(from 3.01 % to 52.17 %), alongside a 10-fold rise in the mean residence time(MRT). Meanwhile, the patch was not irritating. The results of the mechanistic study showed that levulinic acid(LeA) acted as a bridge to increase the interaction between the Tan and the matrix and inhibited the crystallization of the drug in the patch, and THEDES together with CPE improved the matrix fluidity and skin permeability. This study provides a reference for the joint application of THEDES and CPEs in patch development.

Sublingual β-Glucan/Vitamin C-loaded nanoparticle-embedded polyethylene oxide nanofibrous mats

Nutritional supplements available in various forms provide the consumer with essential molecules demanded for well-being retention. Despite the conveniences provided by oral administration, significant disadvantages such as hepatic first-pass effect, limited absorption, and age-related swallowing problems have been recognized which should be addressed appropriately. Nano-sized biomaterials, which have recently gained popularity in numerous medical fields, have the potential to resolve these problems. In this study, a drug delivery system was designed for sublingual administration and fabricated as β-glucan/vitamin C-loaded chitosan/tripolyphosphate/polyvinylpyrrolidone (CS/TPP/PVP) nanoparticles (DNPs) embedded in polyethylene oxide (PEO) nanofibrous mats (DNFs). The optimum PNP size and DNP size for sublingual administration were obtained as 236 ± 1 nm and 257 ± 1 nm, respectively. The homogenous appearance of DNFs was demonstrated and measured as 783 ± 290 nm using scanning electron microscopy. The synthesized biomaterials were analyzed chemically, 3D-wisely, and thermally. The in vitro drug release kinetics investigation concluded that the sustained drug release of DNP over 15 days proceeded based on the first-order model, and 99.30 % of vitamin C and 99.70 % of β-glucan were released. Neither pure nor drug-loaded samples showed notable cytotoxicity in the 24-h 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay in the L929 cell line. Herein, it has been comprehended that DNF nutritional supplement can be a promising novel supplement dosage form with ease of use, high efficiency, and bioavailability than the conventional methods.

Intraoperative contrast-enhanced cone beam CT allows visualization of the ‘dark side’ of the clot and improves mechanical thrombectomy performance

BackgroundVisualization of the clot is key to the endovascular treatment of ischemic stroke, but identification of the distal part of the clot and distal arteries during mechanical thrombectomy (MT) remains...

Enabling oral novel Taxanes-based Chemotherapy with Lipophilic prodrug Self-nanoemulsifying drug delivery system

Larotaxel (LTX) and SB-T-1214 (SBT), two new synthetic experimental toxoids, have shown broad-spectrum antitumor activity, especially against tumors that are resistant to other drugs. However, their poor solubility, membrane permeability, and first-pass effect limits their use in oral administration. We designed and synthesized two long-chain triglyceride-mimic prodrugs of LTX (LTXSSTG) and SBT (SBTSSTG), which are bridged by disulfide bonds and efficiently incorporated them into Self-nanoemulsifying drug delivery system (SNEDDS). These prodrugs can bypass hepatic metabolism by entering the blood through intestinal lymphatic transport, following a similar oral absorption pathway to dietary lipids. It was found that LTXSSTG and SBTSSTG significantly improved oral bioavailability (about 4.5-fold for LTX and 3.4-fold for SBT) compared to their solution forms. Moreover, with LTXSSTG and SBTSSTG incorporating reduction stimulus-responsive spacer were much more effective in suppressing tumor growth in vivo with eliminated adverse effects than solution form. To sum up, this strategy provides a new avenue to enhance oral delivery of new toxoids.