Drug Deposition Research Articles

IBCS: 3. A Biopharmaceutics Classification System for Orally Inhaled Drug Products.

In this article, we specify for the first time a quantitative biopharmaceutics classification system for orally inhaled drugs. To date, orally inhaled drug product developers have lacked a biopharmaceutics classification system like the one developed to navigate the development of immediate release of oral medicines. Guideposts for respiratory drug discovery chemists and inhalation product formulators have been elusive and difficult to identify due to the complexity of pulmonary physiology, the intricacies of drug deposition and disposition in the lungs, and the influence of the inhalation delivery device used to deliver the drug as a respirable aerosol. The development of an inhalation biopharmaceutics classification system (iBCS) was an initiative supported by the Product Quality Research Institute (PQRI). The goal of the PQRI iBCS working group was to generate a qualitative biopharmaceutics classification system that can be utilized by inhalation scientists as a "rule of thumb" to identify desirable molecular properties and recognize and manage CMC product development risks based on physicochemical properties of the drug and the deposited lung dose. Herein, we define the iBCS classes quantitatively according to the dose number and permeability. The proposed iBCS was evaluated for its ability to categorize marketed inhaled drugs using data from the literature. The appropriateness of the classification of each drug was assessed based on published development, clinical and nonclinical data, and mechanistic physiologically based biopharmaceutics modeling. The inhaled drug product development challenges for each iBCS classification are discussed and illustrated for different classes of marketed inhaled drugs. Finally, it is recognized that discriminatory laboratory methods to characterize regional lung deposition, dissolution, and permeability will be key to fully realizing the benefits of an iBCS to streamline and derisk inhaled drug development.

Exploring the therapeutic potential of sodium deoxycholate tailored deformable-emulsomes of etodolac for effective management of arthritis

The current piece of research intends to evaluate the potential of combining etodolac with deformable-emulsomes, a flexible vesicular system, as a promising strategy for the topical therapy of arthritis. The developed carrier system featured nanometric dimensions (102 nm), an improved zeta potential (− 5.05 mV), sustained drug release (31.33%), and enhanced drug deposition (33.13%) of DE-gel vis-à-vis conventional system (10.34% and 14.71%). The amount of permeation of the developed nano formulation across skin layers was demonstrated through CLSM and dermatokinetics studies. The safety profile of deformable-emulsomes has been investigated through in vitro HaCaT cell culture studies and skin compliance studies. The efficacy of the DE-gel formulation was sevenfold higher in case of Xylene induced ear edema model and 2.2-folds in CFA induced arthritis model than that of group treated with conventional gel (p < 0.01). The main technological rationale lies in the use of phospholipid and sodium deoxycholate-based nanoscale flexible lipoidal vesicles, which effectively encapsulate drug molecules within their interiors. This encapsulation enhances the molecular interactions and facilitates the transportation of the drug molecule effectively to the target-site. Hence, these findings offer robust scientific evidence to support additional investigation into the potential utility of flexible vesicular systems as a promising drug delivery alternative for molecules of this nature.

Inhalation Dosage Forms: A Focus on Dry Powder Inhalers and Their Advancements.

In this review, an extensive analysis of dry powder inhalers (DPIs) is offered, focusing on their characteristics, formulation, stability, and manufacturing. The advantages of pulmonary delivery were investigated, as well as the significance of the particle size in drug deposition. The preparation of DPI formulations was also comprehensively explored, including physico-chemical characterization of powders, powder processing techniques, and formulation considerations. In addition to manufacturing procedures, testing methods were also discussed, providing insights into the development and evaluation of DPI formulations. This review also explores the design basics and critical attributes specific to DPIs, highlighting the significance of their optimization to achieve an effective inhalation therapy. Additionally, the morphology and stability of 3 DPI capsules (Spiriva, Braltus, and Onbrez) were investigated, offering valuable insights into the properties of these formulations. Altogether, these findings contribute to a deeper understanding of DPIs and their development, performance, and optimization of inhalation dosage forms.

Bi-directional nasal drug delivery systems: A scoping review of nasal particle deposition patterns and clinical application.

To compare the deposition patterns within the nasal cavity between the bi-directional and unilateral nasal delivery systems. And to summarize the clinical application of the bi-directional nasal drug delivery devices. PubMed, Cochrane Library, Embase, and Web of Science databases. A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). We included studies exploring patterns and influencing factors of particle depositions within the nasal cavity among patients, healthy controls, and nose cast models using the bi-directional and unilateral nasal delivery system. The clinical application of the bi-directional delivery devices was also summarized. A total of 24 studies were included in this review. Bi-directional nasal delivery systems utilize forced exhalation to power the delivery of drugs to deeper areas of the nasal cavity and paranasal sinuses. Unilateral nasal delivery systems included traditional liquid spray pumps, the aerosol mask system, nebulization, and conventional nasal inhalation. Compared with unilateral delivery systems, the bi-directional nasal delivery system provided a more extensive and efficient nasal deposition in the nasal cavity, especially in the olfactory cleft, without lung deposition. Several parameters, including particle size, pulsatile flow, and nasal geometry, could significantly influence nasal deposition. The bi-directional nasal delivery system enables better delivery of steroids or sumatriptan to the sinonasal cavity's high and deep target sites. This bi-directional delivery device demonstrated an effective and well-tolerated treatment that produced high drug utilization, rapid absorption, and sustained symptom improvement among patients with chronic rhinosinusitis (CRS) or migraine. The bi-directional nasal drug delivery systems demonstrated significantly higher drug deposition in superior and posterior regions of the nasal cavity than unilateral nasal delivery systems. Further studies should explore its potential role in delivering drugs to the olfactory cleft among patients with olfactory disorders and central nervous system diseases. N/A.

In Situ Deposition of Drug and Gene Nanoparticles on a Patterned Supramolecular Hydrogel to Construct a Directionally Osteochondral Plug

HighlightsA multifactorial and oriented scaffolds was constructed to stimulate osteochondral regeneration.This is the first demonstration that both drug and gene nanoparticles were spatially deposited on a patterned film through metal-ligand interactions.For the first time, film-rolling approach was employed to construct osteochondral plug to mimick the Haversian canal structure of natural bone.

The effects of aerosol concentration on the evolution, transport, and deposition of hygroscopic droplets in the highly idealized MT model: A numerical study

Inhalation therapy is widely used to treat various respiratory diseases. Nebulizers have been widely adopted due to their ease of operation, high drug delivery efficiency, and low residual volume. Traditional studies on drug delivery in the respiratory tract typically use a one-way coupled method to track drug transport and deposition for non-hygroscopic drug particles. However, neglecting the concentration of nebulized hygroscopic droplet aerosols can lead to significant discrepancies in the deposition efficiency (DE) of nebulized drugs in the airways. To investigate the effect of different nebulization rates on the evolution, transport, and deposition of droplets, a highly idealized mouth-throat (MT) model was selected as a testbed for the in silico trials of drug delivery to the respiratory tract. The interaction between continuous and discrete phases was modeled using a two-way coupled model of highly concentrated droplet aerosol-water vapor interaction, innovated by the particle parcel method. The effects of different coupling methods and boundary conditions on the average droplet diameter and droplet deposition distribution pattern at the outlet of the MT model were compared using a computational fluid dynamics (CFD) method. Simulation results indicate that neglecting the effect of water vapor evaporated from the droplets on the relative humidity (RH) in the oral cavity could lead to a 2.2-fold prediction error of the average droplet diameter at the outlet of the MT model for a conventional nebulization rate of 0.386 g/min. As the nebulization rate increases, the difference in the predicted average droplet diameter at the outlet of the MT model between the one-way coupled method and the two-way coupled method also increases. Increasing the nebulization rate during inhalation therapy could lead to incomplete evaporation of drug droplets, resulting in deposition of larger diameter drug droplets in the oral cavity. In contrast, a lower nebulization rate can reduce the droplet diameter at the outlet of the MT model, allowing it to enter deeper airways.

Comparative investigation of transport and deposition of nebulized particles in nasal airways following various middle turbinectomy.

Topical intranasal medication is required following functional endoscopic sinus surgery (FESS). The optimal particle size of transnasal nebulization aimed at the sinonasal cavities is not conclusive. The current study aims to evaluate the effect of particle size and various surgery scope of middle turbinectomy (MT) on post-full FESS drug delivery to the sinonasal cavities. Sinonasal reconstructions were performed from post-full FESS CT scans in 6 chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Four additional models representing alternative surgery scopes of MT were established from each post-FESS reconstruction for simulation data comparison. Airflow and particle deposition of nebulized delivery were simulated via computational fluid dynamics (CFD) and validated through in vitro experiments. The optimal particle sizes reaching a deposition of at least 75% of the maximum in the targeted regions were identified. The drug deposition rate onto the targeted regions increased following MT, with the greatest deposition following posterior MT (P-MT). Droplets in the range of 18-26 μm reached a deposition of larger than 75% of the maximum onto the targeted regions. Drug delivery rate in the sinonasal cavities varied significantly among individuals and across different types of MT with varying surgical scopes. This study is the first to investigate the effect of various surgery scope on drug delivery by transnasal nebulization to the sinonasal cavities. The findings strongly affirm the vast potential of transnasal nebulization as an effective post-FESS treatment option. Moreover, it emphasizes that the drug delivery process via atomizers to the nasal cavity and paranasal sinuses is highly sensitive to the particle size.

Tailoring Dry Microparticles for Pulmonary Drug Delivery: Ultrasonic Spray Freeze-Drying with Mannitol and Salbutamol Sulphate

Spray freeze-drying has emerged as a valid alternative to traditional spray drying to produce therapeutic dry microparticles. In particular, the spherical shape and high porosity of spray freeze-dried microparticles make them suitable for pulmonary drug delivery through dry powder inhalers. However, an appropriate particle size and fine particle fraction are required to guarantee lung deposition. This study used ultrasonic spray freeze-drying to generate dry microparticles composed of mannitol either alone or added with the bronchodilator salbutamol sulphate. The influence of the solid concentration and the feed flow rate on the particle size, morphology, surface area, porosity, and crystallinity was investigated. Growing particle size was observed, increasing the concentration and feed flow rate. Similarly, the addition of the drug led to a larger particle size and surface area. The in vitro simulation of drug deposition highlighted the dependence of the aerodynamic properties on the solid concentration and feed flow rate. Due to the lower density and particle geometric size, the highest fine particle fraction (26%) and smallest mass median aerodynamic diameter (4.4 μm) were reached at the lowest solid concentration and feed flow rate.

Pioglitazone Nanoparticle Deposited Biologically Active Substrate to Potentiate Antidiabetic Activity

Background:: Diabetes is one of the most escalating endocrine disorders around the global countries. Researchers are paying more attention towards herbal drugs for treating these chronic ailments. As per the statistics, the incidence of diabetes is increasing not only in adults but also in neonates. Herbal plants like Okra and Neem have been used in India since the ages to treat various kinds of ailments. Methods:: The methodology includes the preparation of granules from the okra gum and neem extract, which is compressed into tablets. The nanoparticle dispersion of Pioglitazone is prepared by using the 2% w/v polyvinyl pyrrolidone (PVP) and 1% sodium lauryl sulphate (SLS), which are then sprayed on the drug-free tablet substrate. This process enhances the area of the Pioglitazone particles and thereby increases the bioavailability of the drug. The spraying of the nanoparticles on the surface of the substrate reduces the aggregation of the particles, which is a drawback of nanoparticles. Results:: The results show that the release rate is increased 2.14 times compared with the pure drug by depositing Pioglitazone nanoparticles on a tablet substrate composed of the okra mucilage and alcoholic extract of Neem. It also shows that there is a remarkable reduction in the glucose levels in vivo when compared with the product formulated by employing the traditional wet granulation technique. Conclusion:: This study concluded that the addition of herbal antidiabetic molecules as excipients can improve the therapeutic effect significantly. Better antidiabetic activity may be obtained with the deposition of hydrophobic antidiabetic drugs on herbal antidiabetic components.

The impact of actuator nozzle and surroundings condition on drug delivery using pressurized-metered dose inhalers.

The most commonly used method to deliver aerosolized drugs to the lung is with pressurized metered-dose inhalers (pMDIs). The spray actuator is a critical component of pMDI, since it controls the atomization process by forming aerosol plumes and determining droplet size distribution. Through computational fluid dynamics (CFD) simulations, this study investigated the effect of two different nozzle types (single conventional and twin nozzles) on drug deposition in the mouth-throat (MT) region. We also studied the behavior of aerosol plumes in both an open-air environment and the MT geometry. Our study revealed that spray aerosol generated in an unconfined, open-air environment with no airflow behaves distinctly from spray introduced into the MT geometry in the presence of airflow. In addition, the actuator structure significantly impacts the device's efficacy. In the real MTmodel, we found that the twin nozzle increases drug deposition in the MT region, and its higher aerosol velocity negatively affects its efficiency.

The Pharmacokinetics of Inhaled Drugs.

The pharmacokinetic (PK) profile of a drug after inhalation may differ quite markedly from that seen after dosing by other routes of administration. Drugs may be administered to the lung to elicit a local action or as a portal for systemic delivery of the drug to its site of action elsewhere in the body. Some knowledge of PK is important for both locally- and systemically-acting drugs. For a systemically-acting drug, the plasma concentration-time profile shares some similarities with drug given by the oral or intravenous routes, since the plasma concentrations (after the distribution phase) will be in equilibrium with concentrations at the site of action. For a locally-acting drug, however, the plasma concentrations reflect its fate after it has been absorbed and removed from the airways, and not what is available to its site of action in the lung. Consequently, those typical PK parameters which are determined from plasma concentration measurements, e.g., area under the curve (AUC), Cmax, tmax and post-peak t1/2 may provide information on the deposition and absorption of drugs from the lung; however, the information from these parameters becomes more complicated to decipher for those drugs which are locally-acting in the lung. Additionally, the plasma concentration profile for both locally- and systemically-acting drugs will not only reflect drug absorbed from the lung but also that absorbed from the gastrointestinal (GI) tract from the portion of the dose which is swallowed. This absorption from the GI tract adds a further complication to the interpretation of plasma concentrations, particularly for locally-acting drugs. The influence of physiological and pathological factors needs to be considered in the absorption of some inhaled drugs. The absorption of some hydrophilic drugs is influenced by the inspiratory maneuver used during initial inhalation of the drug, and at later times after deposition. Similarly, the effects of smoking have been shown to increase lung permeability and increase the absorption of certain hydrophilic drugs. The effects of different disease states of the lung have less defined influences on absorption into the systemic circulation.

Effects of vocal fold adduction on the particle deposition in the glottis: A numerical analysis and in vitro assessment

BackgroundThe efficacy of inhalation therapy depends on the drug deposition in the human respiratory tract. This study investigates the effects of vocal fold adduction on the particle deposition in the glottis. MethodsA realistic mouth-throat (MT) geometry was built based on CT images of a healthy adult (MT-A). Mild (MT-B) and great (MT-C) vocal fold (VF) adduction were incorporated in the original model. Monodisperse particles range in size from 3 to 12 μm were simulated at inspiration flow rates of 15, 30 and 45 L per minute (LPM). The regional deposition of drug aerosols was performed in 3D-printed models and quantified using high-performance liquid chromatography. ResultsBoth the numerical analysis and in vitro experiments show that most particles are deposited in the mouth, pharynx and supraglottis, while few are deposited in the glottis and subglottis. For most cases in MT-A, the particle quantity in glottis is lower than 0.02 N/mm2 at 15 and 30 LPM while they increase dramatically at 45 LPM. It peaked at 0.347 N/mm2 for 5-μm particles at 45 LPM in MT-B and 2.324 N/mm2 for 6-μm particles at 30 LPM in MT-C. The lowest drug mass faction in the glottis in vitro were found at 15 LPM for MT-A and MT-C, and at 30 LPM for MT-B, whereas it peaked at 45 LPM for all MT models, 0.71% in MT-A, 1.16% in MT-B, and 2.53% in MT-C, respectively. ConclusionBased on the results of this study, larger particles are more likely to be deposited in the oral cavity, oropharynx, and supraglottis than in the glottis. However, particle deposition in the glottis generally increases with VF adduction and greater inspiratory flow rates.

Deep learning‐based surrogate modeling of coronary in‐stent restenosis

AbstractCoronary artery disease (CAD) is one of the largest causes of death worldwide. Percutaneous coronary intervention (PCI) is a minimally invasive procedure to restore blood flow in blocked coronary arteries. However, PCI carries risks such as in‐stent restenosis and thrombosis. Drug‐eluting stents were developed to counteract the restenosis observed after stent implantation. An effective in silico model that can accurately predict the restenosis procedure is of great importance for the cardiology. This study aims to develop a deep learning‐based surrogate model for in‐stent restenosis incorporating anti‐inflammatory drugs embedded in the drug‐eluting stents. The model includes a detailed multiphysics approach based on partial differential equations (PDEs) to capture platelet aggregation, growth‐factor release, cellular motility and drug deposition.

Conversion of liquid chitosan-based nanoemulsions into inhalable solid microparticles: Process challenges with polysaccharide

Solid particles ≤5 μm are essential to allow lower lung deposition and macrophage phagocytosis of anti-tubercular drugs. Decorating liquid nanoemulsion of anti-tubercular drug with macrophage-specific chitosan and chitosan-folate conjugate and spray drying the nanoemulsion with lactose produced oversized solid particles due to polysaccharide binding effects. This study designed solid nanoemulsion using lactose as the primary solid carrier and explored additives and spray-drying variables to reduce the binding and particle growth effects of chitosan. Deposition of magnesium stearate on lactose negated chitosan-inducible excessive lactose-liquid nanoemulsion binding and solid particle growth. Moderating the adhesion of chitosan-decorated liquid nanoemulsion onto lactose produced smooth-surface solid microparticles (size: 5.45 ± 0.26 μm; roughness: ∼80 nm) with heterogeneous size (span: 1.87 ± 1.21) through plasticization of constituent materials of nanoemulsion and lactose involving OH/N-H, C-H, CONH and/or COO moieties. Smaller solid particles could attach onto the larger particles with minimal steric hindrance by smooth surfaces. Together with round solid particulate structures (circularity: 0.919 ± 0.002), good pulmonary inhalation beneficial for treatment of pulmonary tuberculosis as well as other diseases is conferred.

In Vivo Fluticasone Absorption in Surgical Patients.

Intranasal corticosteroids (INCS) are a treatment mainstay of chronic rhinosinusitis and allergic rhinitis. Current computational models demonstrate that >90% of INCS drug deposition occurs on the head of the inferior turbinate and nasal valve, rather than the actual sinuses. These models do not consider mucociliary clearance which propels mucus posteriorly, nor do they consider the absorption of the drug. The purpose of this study is to better understand the exact anatomical location where INCS are absorbed. Patients with chronic rhinosinusitis and allergic rhinitis taking fluticasone pre-operatively who were scheduled for functional endoscopic sinus surgery and inferior turbinate reduction, respectively, were recruited. Intra-operative tissue samples were obtained from predetermined locations within the sinonasal cavity. Mass spectrometry was then used to quantify the amount of absorption in each specific anatomic location to determine the largest amount of absorption. Eighteen patients were included in our study. The greatest fluticasone absorption levels across the sinonasal anatomy were at the anterior inferior turbinate (5.7 ngl/mL), ethmoid sinus, (4.4 ng/mL), posterior inferior turbinate (3.7 ng/mL), maxillary sinus (1.3 ng/mL), and the sphenoethmoidal recess (0.72 ng/mL) respectively. Absorption was significantly higher in revision surgery compared to surgically naïve patients. Computation fluid dynamic models of the nasal passage are useful models to help predict intranasal particle flow. However, these models do not incorporate or consider the important mucociliary clearance system, leading to absorption of fluticasone throughout the sinonasal cavity far beyond that predicted by these models. 2 Laryngoscope, 134:1551-1555, 2024.

Refractory post-surgical cystoid macular edema managed following suprachoroidal microcatheterization and delivery of triamcinolone

BackgroundPost-surgical macular edema (ME) is a common cause of prolonged visual impairment. Here we report on the feasibility and clinical outcomes from the use of a novel suprachoroidal microcatheter to treat post-surgical chronic ME by the posterior suprachoroidal placement of a triamcinolone acetonide (TA) suspension.MethodsTwo patients were catheterized with the Oxulumis suprachoroidal delivery system on two separate occasions starting 5 and 10 mm posterior to the limbus. The catheter only remains in the suprachoroidal space for the time of the drug administration. Visual acuity and spectral domain optical coherence tomography (SD-OCT) changes were followed over several weeks to months to determine the duration of ME resolution.ResultsSuprachoroidal microcatheterization for posterior delivery of triamcinolone was possible in all attempts using the illuminated Oxulumis catheter. No reflux, scleral or choroidal trauma was observed. There was no intraocular pressure rise during the follow-up period. The triamcinolone deposit was visible on infrared imaging and on SD-OCT a choroidal elevation was visible. Both progressively disappeared over time. A rapid resolution of ME associated with improved vision was observed following each injection for 3 to 7 months with a TA dose of 2.4 mg or 4 mg.ConclusionsIn these patients with poorly responsive ME, posterior suprachoroidal TA led to a visible suprachoroidal drug deposit and prolonged visual improvement. The Oxulumis microcatheterization device performed as expected and was not associated with any complications.

Inhalable spray-dried polycaprolactone-based microparticles of Sorafenib Tosylate with promising efficacy on A549 cells

The study developed and evaluated Sorafenib Tosylate (SRT)-loaded polymeric microparticles (MPs) using biodegradable polymer polycaprolactone (PCL) as a potential inhalable carrier for NSCLC. MPs were prepared by spray-drying an oil-in-water (o/w) emulsion. The optimized MPs demonstrated excellent flowability, particle size of 2.84 ± 0.5 μm, zeta potential of −14.0 ± 1.5 mV, and 85.08 ± 5.43% entrapment efficiency. ATR-FTIR/DSC studies revealed a lack of characteristic peaks of the crystalline drug signifying good entrapment of the drug. MPs were spherical and uniform in SEM pictures. The MPs showed a biphasic release pattern up to 72h. The Anderson cascade impactor (ACI) investigation demonstrated the highest drug deposition at stage 4, which revealed that the MPs can reach the lungs’ secondary and terminal bronchi. Inhalable MPs had an efficient aerodynamic property with a mass median aerodynamic diameter (MMAD) of 2.63 ± 1.3 μm, a geometric standard deviation (GSD) of 1.93 ± 0.2 μm, and a fine particle fraction (FPF) of 87 ± 2.5%. Finally, in cytotoxicity studies on A549 cancer cells, MPs had an IC50 value of 0.6011 ± 0.8 μM, which was 85.68% lower than free drug. These findings suggest SRT-loaded inhalable PCL-based MPs as a novel NSCLC treatment.

In vitro studies on the dependence of drug deposition in dentin on drug concentration, contact time, and the physicochemical properties of the drugs

The chemical analysis of dental hard tissues can provide information on previous drug use due to the deposition of drugs into this tissue. For the interpretation of analytical results in, e.g., postmortem toxicology or regarding archeological samples, the influence of drug dosing, consumption frequency, duration of intake and type of drug on analyte concentrations in teeth has to be characterized. To approximate these correlations, in vitro models were applied to investigate the time dependency of drug deposition via and against pulp pressure (perfusion studies) and the concentration dependency of drug deposition via oral cavity (incubation study) as well as the influence of de- and remineralization (pH cycling) on the incorporation of drugs in bovine dentin pellets. Some of the drugs of abuse most relevant in forensic case work (amphetamines, opiates, cocaine and benzoylecgonine) were applied. Concentrations in dentin samples were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS) after pulverization and extraction via ultrasonication with methanol. The studies showed that drug deposition in dentin likely depends on the physicochemical properties of the drug molecules as well as on the duration of contact with drugs via the blood stream and on drug concentrations present in the oral cavity. Higher drug concentrations in teeth can result from a more frequent or longer drug use. In addition, intake of higher doses or oral/inhalative consumption can also be expected to lead to higher drug concentrations. These findings can be helpful for the interpretation of postmortem cases.

Intestinal Villi-Inspired Mathematically Base-Layer Engineered Microneedles (IMBEMs) for Effective Molecular Exchange during Biomarker Enrichment and Drug Deposition in Diversified Mucosa.

The mucosa-interfacing systems based on bioinspired engineering design for sampling/drug delivery have manifested crucial potential for the monitoring of infectious diseases and the treatment of mucosa-related diseases. However, their efficiency and validity are severely restricted by limited contact area for molecular transfer and dissatisfactory capture/detachment capability. Herein, inspired by the multilayer villus structure of the small intestine that enables high nutrient absorption, a trigonometric function-based periodic pattern was fabricated and integrated on the base layer of the microneedle patch, exhibiting a desirable synergistic effect with needle tips for deep sample enrichment and promising molecular transfer, significantly improving the device-mucosa bidirectional interaction. Moreover, mathematical modeling and finite element analysis were adopted to visualize and quantify the microcosmic molecular transmission process, guiding parameter optimization in actual situation. Encouragingly, these intestinal villi-inspired mathematically base-layer engineered microneedles (IMBEMs) have demonstrated distinguished applicability among mucosa tissue with varying surface curvatures, tissue toughness, and local environments, and simultaneously, have gained favorable support from healthy volunteers receiving preliminary test of IMBEMs patches. Overall, validated by numerous in vitro and in vivo tests, the IMBEMs were confirmed to act as a promising candidate to facilitate mucosa-based sampling and topical drug delivery, indicating highly clinical translation potential.

Formulation optimization, in vitro and in vivo evaluation of niosomal nanocarriers for enhanced topical delivery of cetirizine

Cetirizine hydrochloride (CTZ), a second-generation anti-histaminic drug, has been recently explored for its effectiveness in the treatment of alopecia. Niosomes are surfactant-based nanovesicular systems that have promising applications in both topical and transdermal drug delivery. The aim of this study was to design topical CTZ niosomes for management of alopecia. Thin film hydration technique was implemented for the fabrication of CTZ niosomes. The niosomes were examined for vesicle size, surface charge, and entrapment efficiency. The optimized niosomal formulation was incorporated into a hydrogel base (HPMC) and explored for physical characteristics, ex vivo permeation, and in vivo dermato-kinetic study. The optimized CTZ-loaded niosomal formulation showed an average size of 403.4 ± 15.6 nm, zeta potential of − 12.9 ± 1.7 mV, and entrapment efficiency percentage of 52.8 ± 1.9%. Compared to plain drug solution, entrapment of CTZ within niosomes significantly prolonged in vitro drug release up to 12 h. Most importantly, ex-vivo skin deposition studies and in vivo dermato-kinetic studies verified superior skin deposition/retention of CTZ from CTZ-loaded niosomal gels, compared to plain CTZ gel. CTZ-loaded niosomal gel permitted higher drug deposition percentage (19.2 ± 1.9%) and skin retention (AUC0-10h 1124.5 ± 87.9 μg/mL.h) of CTZ, compared to 7.52 ± 0.7% and 646.2 ± 44.6 μg/mL.h for plain CTZ gel, respectively. Collectively, niosomes might represent a promising carrier for the cutaneous delivery of cetirizine for the topical management of alopecia.