Drug Delivery Module Research Articles

COST-EFFECTIVENESS ANALYSIS OF IN SILICO CLINICAL TRIALS OF VASCULAR STENTS

Today, it takes ten to twelve years on average to complete a clinical trial before a new drug is approved and brought to marktet. Moreover, the evaluation of the efficacy and safety of drugs or devices has been performed in the linear and sequential manner with limited change over the past decade. The InSilc project is an EU funded project (www.insilc.eu) within which the InSilc platform was developed for designing, developing and assessing coronary stents. The InSilc platform contains the following modules: Mechanical Modelling Module, 3D Reconstruction and Plaque Characterization Tool, Deployment Module, Fluid Dynamics Module, Drug Delivery Module, Degradation Module, Myocardial Perfusion Module, Virtual Population Physiology and Virtual Population Database. We analyze the cost of three different in silico scenarios for clinical study. In Scenario 1, two different stent designs are compared according to the ISO standard for in silico mechanical tests. Scenario 2 predicts the stenting outcome for a virtual anatomy where design/material could be changed. Scenario 3 compares two stents using the same virtual anatomies from the Virtual vessel database. Cost-effectiveness analysis was performed for real clinical trials with metallic and BVS stent and in silico clinical trials. It was observed that in silico clinical trials are almost 90 times cheaper than real clinical trials for 1000 patients. In Silico clinical trials will not completely replace real clinical studies but the evidence shows that they can significantly reduce the cost of a real clinical study which will open a new avenue for future hybrid real and in silico clinical trials.

SPIONs Conjugate Supported Anticancer Drug Doxorubicin's Delivery: Current Status, Challenges, and Prospects.

Considerable efforts have been directed towards development of nano-structured carriers to overcome the limitations of anticancer drug, doxorubicin’s, delivery to various cancer sites. The drug’s severe toxicity to cardio and hepatic systems, low therapeutic outcomes, inappropriate dose–demands, metastatic and general resistance, together with non-selectivity of the drug have led to the development of superparamagnetic iron oxide nanoparticles (SPIONs)-based drug delivery modules. Nano-scale polymeric co-encapsulation of the drug, doxorubicin, with SPIONs, the SPIONs surface end-groups’ cappings with small molecular entities, as well as structural modifications of the SPIONs’ surface-located functional end-groups, to attach the doxorubicin, have been achieved through chemical bonding by conjugation and cross-linking of natural and synthetic polymers, attachments of SPIONs made directly to the non-polymeric entities, and attachments made through mediation of molecular-spacer as well as non-spacer mediated attachments of several types of chemical entities, together with the physico-chemical bondings of the moieties, e.g., peptides, proteins, antibodies, antigens, aptamers, glycoproteins, and enzymes, etc. to the SPIONs which are capable of targeting multiple kinds of cancerous sites, have provided stable and functional SPIONs–based nano-carriers suitable for the systemic, and in vitro deliveries, together with being suitable for other biomedical/biotechnical applications. Together with the SPIONs inherent properties, and ability to respond to magnetic resonance, fluorescence-directed, dual-module, and molecular-level tumor imaging; as well as multi-modular cancer cell targeting; magnetic-field-inducible drug-elution capacity, and the SPIONs’ magnetometry-led feasibility to reach cancer action sites have made sensing, imaging, and drug and other payloads deliveries to cancerous sites for cancer treatment a viable option. Innovations in the preparation of SPIONs-based delivery modules, as biocompatible carriers; development of delivery route modalities; approaches to enhancing their drug delivery-cum-bioavailability have explicitly established the SPIONs’ versatility for oncological theranostics and imaging. The current review outlines the development of various SPIONs-based nano-carriers for targeted doxorubicin delivery to different cancer sites through multiple methods, modalities, and materials, wherein high-potential nano-structured platforms have been conceptualized, developed, and tested for, both, in vivo and in vitro conditions. The current state of the knowledge in this arena have provided definite dose-control, site-specificity, stability, transport feasibility, and effective onsite drug de-loading, however, with certain limitations, and these shortcomings have opened the field for further advancements by identifying the bottlenecks, suggestive and plausible remediation, as well as more clear directions for future development.

Engineered Bacteria with Genetic Circuits Accumulating Nanomagnets as MRI Contrast Agents.

The demand for highly efficient cancer diagnostic tools increases alongside the high cancer incidence nowadays. Moreover, there is an imperative need for novel cancer treatment therapies that lack the side effects of conventional treatment options. Developments in this aspect employ magnetic nanoparticles (MNPs) for biomedical applications due to their stability, biocompatibility, and magnetic properties. Certain organisms, including many bacteria, can synthesize magnetic nanocrystals, which help their spatial orientation and survival by sensing the earth's geomagnetic field. This work aims to convert Escherichia coli to accumulate magnetite, which can further be coupled with drug delivery modules. The authors design magnetite accumulating bacterial machines using genetic circuitries hiring Mms6 with iron-binding activity and essential in magnetite crystal formation. The work demonstrates that the combinatorial effect of Mms6 with ferroxidase, iron transporter protein, and material binding peptide enhances the paramagnetic behavior of the cells in magnetic resonance imaging (MRI) measurements. Cellular machines are also engineered to display Mms6 peptide on the cell surface via an autotransporter protein that shows augmented MRI performance. The findings are promising for endowing a probiotic bacterium, able to accumulate magnetite intracellularly or extracellularly, serving as a theranostics agent for cancer diagnostics via MRI scanning and hyperthermia treatment.

Cucurbituril-Based Supramolecular Assemblies: Prospective on Drug Delivery, Sensing, Separation, and Catalytic Applications.

Precise control over the stimuli-responsive noncovalent interactions operative in a complex molecular system has emerged as a convenient way to realize applications in the detection and sensing of trace analytes, metal ion separation, uptake-release, in situ nanoparticle synthesis, and catalytic activity. This feature article focuses on the attributes and advantages of noncovalent host-guest interactions involving cucurbituril homologues (CBs) with a wide range of organic and inorganic guests, starting from organic dyes to drugs, proteins, surfactants, metal ions, and polyoxometalates. The unique structural features of CBs provide interaction sites for cations at the portals, polyanions at the periphery, and hydrophobic groups in its cavity. The facile complexation and consequent compositional and geometrical arrangements of guests such as naphthalenediimides, coumarins, porphyrins, and triphenylpyrylium ions with the host CBs led to remarkable changes in many molecular properties, especially aggregation, the proton binding and release affinity, and novel emissive dimers, and each of such spectroscopic signatures have been appropriately channeled to drug delivery and activation to improve the antibacterial efficacy and shelf life of drugs by increasing their photostability. Several technological advantages have also been extracted from the interaction of CBs with inorganic guests as well. The interaction of CB7 with the heptamolybdate anion resulted in the precipitation of a hybrid complex material which enabled a convenient separation methodology for the use of clinically pure radioactive 99mTc in diagnostic applications. Certain cucurbituril-based hybrid materials have been developed for enhanced SO2 adsorption at low pressures, high-efficiency hydrogen production, and reversible catalytic systems. Thus, this feature article provides a glimpse of the vast potential of cucurbituril homologues with organic and inorganic guests and calls for a dedicated effort to explore supramolecular strategies for better sensors, therapeutics, smart drug delivery modules, and facile devices.

Formulation and evaluation of atorvastatin calcium niosomes

Atorvastatin calcium is a HMG-CoA reductase inhibitor used for the treatment of hyperlipidaemia. It has oral bioavailability of ≤12 %. It also undergoes high first pass metabolism. It is highly soluble in acidic pH and absorbed more in the upper part of the gastrointestinal tract. In order, to improve the absorption and its oral bioavailability, niosomes of Atorvastatin calcium have been formulated and evaluated on different parameters. Niosomes play an increasingly important role in drug delivery as they can reduce toxicity and 000000000modify pharmacokinetic and bio-availability. Niosomes formulations of Atorvastatin calcium were successfully developed by thin film hydration technique using nonionic surfactant i.e. Span 40, Span 60 Span 80, Tween 20, Tween 40, Tween 80 and cholesterol at different concentrations. The formulations were evaluated for size, shape, and entrapment efficiency. In-vitro release and stability studies also performed. Results indicated that Niosomes were prepared succesfully work as promising drug carriers and promising drug delivery module.

Extensive early mineralization of pre-osteoblasts, inhibition of osteoclastogenesis and faster peri-implant bone healing in osteoporotic rat model: principle effectiveness of bone-specific delivery of Tibolone as evaluated in vitro and in vivo

Hydrophobic drug molecules pose a significant challenge in immobilization on super-hydrophobic metallic surfaces like conventional titanium implants. Pre-coating surface modifications may yield a better platform with improved wettability for such purposes. Such modifications, as depicted in this study, were hypothesized to provide the requisite roughness to assist deposition of polymers like silk fibroin (SF) as a drug-binding matrix in addition to significant improvement in early protein adsorption, which facilitates faster cellular adhesion and proliferation. A silk-based localized drug delivery module was developed on the titanium surface and tested for its surface roughness, wettability, biocompatibility and in vitro differentiation potential of cells cultured on the coated metallic surfaces with/without external supplementation of the active metabolite of Tibolone. Conditioning of the matrix-coated implants with osteogenic as well as osteoclastogenic media supplemented with Tibolone stimulated the expression of early osteogenic gene and calcium deposition in the extracellular matrix. Significant inhibition in resorptive activity was also observed in the presence of the drug. To assess the efficacy of localized delivery of Tibolone via topographically modified titanium implants for inducing early peri-implant bone formation, osteoporosis was artificially induced in rats subjected to bilateral ovariectomy and implants were placed thereafter. Bone-specific release of Tibolone through the biomimetic matrix in osteoporotic rats collectively indicated significant improvement in peri-implant bone growth after 2 and 4 weeks (p < 0.05 compared to dummy-coated implants). These findings demonstrate for the first time that Tibolone released from SF matrix-coated implants can accelerate the biological stability of bone fixtures.

Niosomes as efficient drug delivery modules for encapsulation of Toll-like receptor 7 agonists and IDO-inhibitor

The present study delineates the formulation of niosomes as drug encapsulating assemblies via. sonication method. In this report, for the first time, 1-benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (BBIQ) and 1-methyl-D-tryptophan (D-1MT/Indoximod) were encapsulated in niosomes and further characterized using particle size and microscopic analysis. BBIQ [Toll-like receptor (TLR) 7 agonist] and D-1MT [Indoleamine2, 3-dioxygenase (IDO) inhibitor] are the immunomodulating drugs that can be used in several vaccines such as malaria, influenza, and cancer. Stability and solubility studies of nascent and drug-loaded niosomes were carried out to obtain the best formulation of BBIQ, D-1MT, and their combination. Typically, blank and drug-loaded niosomes of higher entrapment efficiencies (>90%) were observed. Fourier transform infrared spectroscopy was employed to study the drug interaction with niosomes. Release studies and kinetic modeling have been carried out to investigate the release behavior of drugs from the niosomes. Fluorescence probe quenching technique has been employed to determine the location and distribution coefficient of the drugloaded in the niosomes. The results obtained show niosomes as promising vehicles for the co-delivery of TLR7 agonist with IDO-inhibitor which can be explored in cancer vaccine.

Medical Microrobot — A Drug Delivery Capsule Endoscope with Active Locomotion and Drug Release Mechanism: Proof of Concept

This paper presents a robotic capsule endoscope integrated a targeted drug delivery module (DDM) for digestive diseases treatments. The capsule with a big permanent magnet inside is wirelessly controlled and actively moves to target region in gastrointestinal tract by an electromagnetic actuation system (EMA). DDM is a separated body composed of a drug container and a non-power drug-releasing mechanism. The force to expel drug is generated by carbon dioxide gas pressure coming from a chemical reaction inside a propellant reservoir. Where the chemical reaction is activated by a mechanical mechanism that allows dry chemical powders contacting with water at the target point. A small permanent magnet is utilized to separate reagents and wet paper before drug injection. It is designed to be stable during locomotion by virtue of the attractive force of a big permanent magnet. To trigger releasing mechanism, gradient magnetic field from EMA system is created to push small magnet slide down, which allows reagents drop and contact with water in wet paper. The designed DDM has length of 11 mm and diameter of 11 mm. The proposed robotic capsule could show high potentials to be utilized for therapeutic treatment of digestive diseases in practical clinical sites through simulation and ex-vivo experiments.

Advancement in Novel Drug Delivery System: Niosomes

Niosomes represent a promising drug delivery module. Noisome same as to liposome and Noisome represent alternative vesicular drug delivery systems with respect to liposomes, due to the noisome ability to encapsulate the different type of drugs within their multi environmental structure. Niosomes are thoughts to be a better system for drug delivery as compared to liposomes due to various factors like cost, stability etc. They are many types of drug deliveries that can be possible using niosomes like targeting, ophthalmic, topical, parenteral, etc. In recent research, comprehensive research carried over noisome as a drug carrier. Various drugs are enlisted and tried in noisome surfactant vesicles. Niosomes proved to better drug carrier system and has the potential to reduce the side effects of drugs and increased therapeutic effectiveness in various diseases. Noisome used more than fifty drugs are tried in niosomal formulations by the intravenous route, per oral administration, trans-dermal route of administration, and inhalation preparation, ocular nasal route of administration. Treatment of infectious diseases and immunization has undergone a revolutionary work in recent years. The large numbers of disease-specific biological have been developed, and also emphasis has been made to effectively deliver these biological. Niosomes shows an emerging class of novel vesicular systems. Niosomes are self-assembled vesicles composed primarily of synthetic surfactant and cholesterol. Comprehensive research carried over noisome as a drug carrier. Various drugs are enlisted and tried in noisome surfactant vesicles. This article presents an overview of the techniques of preparation of noisome, types of noisome, characterization and their applications. Keywords-Niosomes; Method of preparation; Evaluation study; Application of Niosomes

Evaluation of Antiproliferative Activity, Safety and Biodistribution of Oxaliplatin and 5-Fluorouracil Loaded Lactoferrin Nanoparticles for the Management of Colon Adenocarcinoma: an In Vitro and an In Vivo Study.

Colon adenocarcinoma is the most common form of gastro intestinal tract cancer, predominantly in ageing population. Chemotherapy with 5-Fluorouracil and oxaliplatin is an indispensable treatment regimen, nevertheless having limitation of systemic toxicity and lower therapeutic index. The present study is based on evaluation of anti-proliferative potential, pharmacokinetics parameters, safety profile, biodistribution and efficacy of 5-FU/oxaliplatin loaded lactoferrin nanoparticles in cell lines and wistar rats in order to overcome the above limitation. Nanoparticles were prepared by Water-in-oil process. The anti-proliferative efficacy and mode of cellular entry was evaluated in COLO-205 cells. The pharmacokinetics and biodistribution analysis were performed in healthy rats while efficacy and safety assay were performed in ACF induced rats. 5-FU and oxaliplatin loaded nanoparticles shows enhanced antiproliferative activity as compare to free drugs in COLO-205 cells. Lactoferrin nanoparticles also improve the pharmacokinetics profile, safety parameters and efficacy of 5-FU and Oxaliplatin. Lactoferrin nanoparticles demonstrated an attractive drug delivery module to manage the colon adenocarcinoma as it has improved the antiproliferative activity of 5-FU and Oxaliplatin against colon adenocarcinoma cells. Moreover, it also improves the pharmacokinetic profile and safety parameters of the same drug in wistar rat.

InSilc: 3D Reconstruction and plaque characterization tool.

Coronary artery disease (CAD) is the leading cause of mortality in Europe and worldwide. Atherosclerosis is the most common pathologic process that is highly related with CAD, while the implantation of drug-eluting Bioresorbable Vascular Scaffolds (BVS) is the most promising procedure for treating patients with CAD. InSilc is an textbfin silico clinical trial (ISCT) platform for the development and assessment of drugeluting BVS. The InSilc platform provides insight in the performance of drug-eluting BVS in their short term and medium/long term through the Mechanical Modelling Module, the Deployment Module, the Fluid Dynamics Module, the Myocardial Perfusion Module, the Drug-delivery Module and the Degradation Module. In order for the aforementioned modules to be developed, the utilization of the reconstructed patient specific arterial segment and the BVS design are required, which is achieved through the 3D reconstruction and plaque characterization tool.In this study, the overall architecture of the InSilc platform is presented with special emphasis on the 3D reconstruction and plaque characterization tool. The tool will be able to implement different medical image processing workflows. The workflows will require minimum user intervention in order to be used in large scale clinical trials.

Phototoxicity free quantum dot-based niosome formulation for controlled drug release and its monitoring

A novel niosomes-based system composed of Hypromellose (HPMC) functionalized fluorescent, biocompatible ZnS:Mn quantum dots (QDs), and anti-HIV drug Tenofovir disoproxil fumarate (TDF) was designed. An appropriate ratio of surfactant Sorbitan Monostearate (SPAN-60) and cholesterol was used to obtain an optimal entrapment efficiency. Initially, after observing the successful interaction of HPMC with SPAN-60, the noisome formulation including (QDs + drug) and HPMC-coated QDs was synthesized by a wet chemical route and characterized by X-ray diffraction (XRD), Transmission electron microscope (TEM) and Selected Electron Diffraction (SAED). Secondly, (QDs + drug) loaded niosome formulations were studied by varying the ratio of SPAN-60 and cholesterol. Multiple studies were done to characterize the shape, size, viscosity, colloidal stability, and entrapment efficiency of (QDs + drug) loaded niosomes. Lastly, pH-dependent (QDs + drug) release profiles were studied by a spectroscopic technique considering the pH of the human gastrointestinal region to obtain the formulation stability of (QDs + drug) release from the niosome vesicles. These studies also include pH-dependent photo-stability measurements based on laser-induced multiphoton excitation technique in the Infrared region. The multiphoton time-resolved studies were completed to avoid the UV induced phototoxicity in the drug delivery modules. Current studies on the formulation of niosomes-based (QDs + drug) system laid a foundation to make a complete phototoxicity free system for tracking controlled drug release and its imaging.

Nebulization of Cyclic Arginine-Glycine-(D)-Aspartic Acid-Peptide Grafted and Drug Encapsulated Liposomes for Inhibition of Acute Lung Injury.

Acute lung injury (ALI) is a fatal syndrome in critically ill patients. It is characterized by lung edema and inflammation. Numerous pro-inflammatory mediators are released into alveoli. Among them, interleukin-1beta (IL-1β) causes an increase in solute permeability across the alveolar-capillary barrier leading to edema. It activates key effector cells (alveolar epithelial and endothelial cells) releasing inflammatory chemokines and cytokines. The purpose of the study was to demonstrate that nebulized liposomes inhibit ALI in vivo. In vivo ALI model was simulated through intra-tracheal instillation of IL-1β solution (100μg/mL in PBS, pH7.2, 200μL) in male Sprague-Dawley rats. Various formulations were tested in ALI induced rats. These formulations include plain liposomes (PL), methylprednisolone sodium succinate solution (MPS solution), cRGD-peptide grafted liposomes (LcRGD) and methylprednisolone sodium succinate encapsulated and cRGD-peptide grafted liposomes (MPS-LcRGD). Formulations were nebulized in vivo in rats using micro-pump nebulizer. Liposome formulations exhibited higher levels of drug concentration in lungs. The physicochemical parameters demonstrated that the liposome formulations were stable. On the basis of aerodynamic droplet-size, nebulized formulations were estimated to deposit in different regions of respiratory tract, especially alveolar region, Among the formulations, MPS-LcRGD caused significant reduction of edema, neutrophil infiltration and inflammation biochemical marker levels. From the results, it can be inferred that nebulization of targeted liposomes had facilitated spatial and temporal modulation of drug delivery resulting in alleviation of ALI.

Circulating Magnetic Microbubbles for Localized Real-Time Control of Drug Delivery by Ultrasonography-Guided Magnetic Targeting and Ultrasound.

Image-guided and target-selective modulation of drug delivery by external physical triggers at the site of pathology has the potential to enable tailored control of drug targeting. Magnetic microbubbles that are responsive to magnetic and acoustic modulation and visible to ultrasonography have been proposed as a means to realize this drug targeting strategy. To comply with this strategy in vivo, magnetic microbubbles must circulate systemically and evade deposition in pulmonary capillaries, while also preserving magnetic and acoustic activities in circulation over time. Unfortunately, challenges in fabricating magnetic microbubbles with such characteristics have limited progress in this field. In this report, we develop magnetic microbubbles (MagMB) that display strong magnetic and acoustic activities, while also preserving the ability to circulate systemically and evade pulmonary entrapment.Methods: We systematically evaluated the characteristics of MagMB including their pharmacokinetics, biodistribution, visibility to ultrasonography and amenability to magneto-acoustic modulation in tumor-bearing mice. We further assessed the applicability of MagMB for ultrasonography-guided control of drug targeting.Results: Following intravenous injection, MagMB exhibited a 17- to 90-fold lower pulmonary entrapment compared to previously reported magnetic microbubbles and mimicked circulation persistence of the clinically utilized Definity microbubbles (>10 min). In addition, MagMB could be accumulated in tumor vasculature by magnetic targeting, monitored by ultrasonography and collapsed by focused ultrasound on demand to activate drug deposition at the target. Furthermore, drug delivery to target tumors could be enhanced by adjusting the magneto-acoustic modulation based on ultrasonographic monitoring of MagMB in real-time.Conclusions: Circulating MagMB in conjunction with ultrasonography-guided magneto-acoustic modulation may provide a strategy for tailored minimally-invasive control over drug delivery to target tissues.

Diclofenac sodium loaded liposomal gel for transdermal delivery: Formulation, characterisation and pharmacokinetic evaluation

The transdermal route of drug delivery has many advantages for drug administration in local and systemic therapy. But, skin is widely recognized for its effective barrier properties compared to other biological membranes. The low permeability of the skin makes it a minor port of entry for drugs. The vesicular drug delivery is thus potentially beneficial as vesicles tend to fuse and adhere to the cell surface; this is believed to increase the thermodynamic activity of the drug at stratum corneum interface thus leading to enhanced permeation rate. These vesicles can act as drug reservoirs and modification of their composition or surface can adjust the drug release rate and/or the affinity of the target site. Among different carriers like liposomes, niosomes, ethosomes and transferosomes, represent a promising drug delivery module. The current research Aims to develop diclofenac sodium loaded liposomal gel for effective transdermal delivery. Diclofenac sodium is a highly lipophilic non-steroidal anti-inflammatory drug. The Aim of the present study is to formulate and optimize Diclofenac sodium loaded liposomes by film hydration technique using HSPC as the lipid base and cholesterol as the stabilizer and then to carry out drug and excipient interaction studies (using DSC and FTIR) and pharmacokinetic evaluation of selected products on male Wistar rats and to evaluate the stability of the selected products as per suitable stability testing protocol following ICH guidelines.

Perspective Insights into Disease Progression, Diagnostics, and Therapeutic Approaches in Alzheimer's Disease: A Judicious Update

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive accumulation of β-amyloid fibrils and abnormal tau proteins in and outside of neurons. Representing a common form of dementia, aggravation of AD with age increases the morbidity rate among the elderly. Although, mutations in the ApoE4 act as potent risk factors for sporadic AD, familial AD arises through malfunctioning of APP, PSEN-1, and−2 genes. AD progresses through accumulation of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) in brain, which interfere with neuronal communication. Cellular stress that arises through mitochondrial dysfunction, endoplasmic reticulum malfunction, and autophagy contributes significantly to the pathogenesis of AD. With high accuracy in disease diagnostics, Aβ deposition and phosphorylated tau (p-tau) are useful core biomarkers in the cerebrospinal fluid (CSF) of AD patients. Although five drugs are approved for treatment in AD, their failures in achieving complete disease cure has shifted studies toward a series of molecules capable of acting against Aβ and p-tau. Failure of biologics or compounds to cross the blood-brain barrier (BBB) in most cases advocates development of an efficient drug delivery system. Though liposomes and polymeric nanoparticles are widely adopted for drug delivery modules, their use in delivering drugs across the BBB has been overtaken by exosomes, owing to their promising results in reducing disease progression.

Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module.

Electrochemical analysis of sweat using soft bioelectronics on human skin provides a new route for noninvasive glucose monitoring without painful blood collection. However, sweat-based glucose sensing still faces many challenges, such as difficulty in sweat collection, activity variation of glucose oxidase due to lactic acid secretion and ambient temperature changes, and delamination of the enzyme when exposed to mechanical friction and skin deformation. Precise point-of-care therapy in response to the measured glucose levels is still very challenging. We present a wearable/disposable sweat-based glucose monitoring device integrated with a feedback transdermal drug delivery module. Careful multilayer patch design and miniaturization of sensors increase the efficiency of the sweat collection and sensing process. Multimodal glucose sensing, as well as its real-time correction based on pH, temperature, and humidity measurements, maximizes the accuracy of the sensing. The minimal layout design of the same sensors also enables a strip-type disposable device. Drugs for the feedback transdermal therapy are loaded on two different temperature-responsive phase change nanoparticles. These nanoparticles are embedded in hyaluronic acid hydrogel microneedles, which are additionally coated with phase change materials. This enables multistage, spatially patterned, and precisely controlled drug release in response to the patient's glucose level. The system provides a novel closed-loop solution for the noninvasive sweat-based management of diabetes mellitus.

DESIGN AND STATISTICAL EVALUATION OF A MULTIUNIT DELIVERY SYSTEM CONTAINING NISOLDIPINE-SOLUPLUS® SOLID DISPERSION FOR HYPERTENSION CHRONOTHERAPY

&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To study the mechanism and factors affecting the design of an industrially scalable formulation in a combined drug delivery module containing solid dispersion (SD) multiunit pellets with novel polymer Soluplus® in a modified release system to address chronotherapeutic needs of hypertension therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Nisoldipine-Soluplus® SD pellet formulations were prepared using the central composite design of experiments (CCD) to study the effect of inert core level and drug to polymer ratio. The solid dispersions were formed on inert pellets surface by fluidized bed coating and characterized by dissolution efficiency and time for 90% drug release. The data was statistically analyzed to develop a response surface for optimum SD formulation in pellets. The SD pellets were characterized by FTIR, DSC and SEM. The optimum formulation of SD coated pellets was further coated with Eudragit S100-L100 polymer mix and characterized for dissolution in multimedia and two-step dissolution for lag time.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A response surface was developed for highest dissolution efficiency (%DE) and least time to release 90% drug (T&lt;sub&gt;90&lt;/sub&gt;). The model was significant, and the role of core pellets was found to be more significant than the drug-polymer ratio. The study of the desirability function indicated that a polymer content of 75% and inert core level to yield 23% net weight gain, provided optimum dissolution enhanced SD pellets. The drug was found to exist in amorphous form. The final capsules containing Eudragit S100-L100 coated delayed release SD pellets showed a lag time of 2 h and a definite pH-gradient towards drug release.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The findings from this study helped to understand the mechanism, design and factors affecting drug release from a delayed release SD system for a poorly soluble drug for potential hypertension chronotherapy.&lt;/p&gt;

Synthesis and evaluation of isometamidium-alginate nanoparticles on equine mononuclear and red blood cells

Isometamidium hydrochloride (ISMM) is an effective drug for the treatment of trypanosomosis, but it causes local and systemic toxicity. Isometamidium hydrochloride has limited therapeutic index and exhibit considerable variation in their prophylactic activities. We developed a trypanocidal nanoformulation using ISMM and polymers sodium alginate/gum acacia to enhance the efficacy of the drug at lower doses, while minimizing undesirable side effects. It was characterized by transmission electron microscopy and infrared spectroscopy for evaluation of size, morphology, functional groups, etc. In vitro cytotoxicity studies were performed by metabolic resazurin assay at different concentrations of isometamidium-loaded alginate/gum acacia nanoparticles using equine peripheral blood mononuclear cells. Hemolytic assay revealed significantly less toxicity compared to the conventional drug. The results demonstrate that the developed drug delivery module can be evaluated in suitable animal models to evaluate its potency.

A soft-magnet-based drug-delivery module for active locomotive intestinal capsule endoscopy using an electromagnetic actuation system

Nowadays, capsule endoscope (CE) technology is highly evaluated as a promising medical apparatus for minimally invasive diagnosis and therapy. Active locomotive capsule endoscopy (ALICE) using an electromagnetic actuation (EMA) system is one of the new state-of-the-art solutions that effectively increase the diagnostic ability of CE. Together with a locomotive CE, there are various requests for multifunctional modules that can deliver drugs or execute biopsy functions. This paper presents a drug delivery module for ALICE using EMA, where we adopt a soft magnet due to its special physical properties. The drug-delivery module consists of two ring-type soft magnets and a simple plastic hinge; it has a volume of 0.78ml, which is approximately 26% the total volume of a conventional active CE. The drug-delivery module can be integrated with ALICE. First, the drug is encapsulated into the module by the attracting force between two axially magnetized soft-magnetic rings. Second, ALICE with the drug delivery module can be driven by a precisely controlled external magnetic field to investigate and situate correct drug delivery to a target lesion. Third, at the target lesion, the external magnetic field is turned off and the two axial magnetized soft-magnetic rings of the drug-delivery module are demagnetized. Fourth, when we apply a strong pulsating magnetic field in a radial direction, the drug-delivery module is opened by the repulsive force between the two radially magnetized soft-magnetic rings, and the encapsulated drug can be released. After the drug release, the drug-delivery module can be returned to its initial shape thanks to an integrated plastic hinge in the drug delivery module and the attracting force between two axially magnetized soft-magnetic rings. Finally, the active CE can continue to show its intrinsic diagnostic work. Consequently, we demonstrate the feasibility of the drug-delivery module which is integrated in ALICE.