Drug Diffusion Research Articles

Optimizing vancomycin release from novel carbon fiber-reinforced polymer implants with small holes: periprosthetic joint infection treatment.

Periprosthetic joint infection (PJI) is a catastrophic complication after total hip arthroplasty. A new drug-loaded carbon fiber-reinforced polymer (CFRP) prosthesis with a sustained drug-release mechanism is being developed for one-stage surgery. We aimed to examine the diffusion dynamics of vancomycin from vancomycin paste-loaded CFRP implants. The differences in the in vitro diffusion dynamics of vancomycin paste were investigated using the elution test by varying parameters. These included the mixing ratio of vancomycin and distilled water (1:0.8, 1:1.2, and 1:1.4) for vancomycin paste, and hole diameter (1mm and 2mm) on the container. The in vivo diffusion dynamics were investigated using a rabbit model with vancomycin-loaded CFRP implants placed subcutaneously. The in vitro experiments showed that the diffusion effect of vancomycin was highest in the parameters of vancomycin paste with distilled water mixed in a ratio of 1:1.4, and with a 2mm hole diameter. The in vivo experiments revealed diffusion dynamics similar to those observed in the in vitro study. The drug diffusion effect tended to be high for vancomycin paste with a large water ratio, and a large diameter of holes. These results indicate that the drug diffusion dynamics from a CFRP implant with holes can be adjusted by varying the water ratio of the vancomycin paste, and the hole size on the CFRP implant.

Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug.

The purpose of the present work was to develop nanoemulsion-based formulations of mirtazapine for intranasal delivery using a spray actuator to target the brain for treating depression. Research on the solubility of medications in different oils, surfactants, co-surfactants, and solvents has been done. Using pseudo-ternary phase diagrams, the various ratios of the surfactant and co-surfactant mix were computed. Thermotriggered nanoemulsion was formulated using different concentrations of poloxamer 407 (i.e., 15%, 15.5%, 16%, 16.5% up to 22%). Similarly, mucoadhesive nanoemulsion using 0.1% Carbopol and water-based plain nanoemulsions were also prepared for comparative assessment. The developed nanoemulsions were analyzed for physicochemical properties, i.e., physical appearance, pH, viscosity, and drug content. Drug-excipient incompatibility was determined by Fourier transform infrared spectral (FTIR) analysis and differential scanning calorimetry (DSC). In vitro drug diffusion studies were conducted for optimized formulations. Among the three formulations, RD1 showed the highest percentage of drug release. Ex vivo drug diffusion studies were conducted on freshly excised sheep nasal mucosa with Franz diffusion cell simulated nasal fluid (SNF) for all three formulations up to 6 h, and the thermotriggered nanoemulsion (RD1) showed 71.42% drug release with 42.64 nm particle size and a poly dispersity index of 0.354. The zeta potential was found to be -6.58. Based on the above data, it was concluded that thermotriggered nanoemulsion (RD1) has great potential to be used as an intranasal gel for treating depression in patients. It can offer great benefits by reducing dosing frequency and improving bioavailability of mirtazapine by direct nose-to-brain delivery.

Changes in local tissue microenvironment in response to subcutaneous long-acting delivery of tenofovir alafenamide in rats and non-human primates.

Several implantable long-acting (LA) delivery systems have been developed for sustained subcutaneous administration of tenofovir alafenamide (TAF), a potent and effective nucleotide reverse transcriptase inhibitor used for HIV pre-exposure prophylaxis (PrEP). LA platforms aim to address the lack of adherence to oral regimens, which has impaired PrEP efficacy. Despite extensive investigations in this field, tissue response to sustained subcutaneous TAF delivery remains to be elucidated as contrasting preclinical results have been reported in the literature. To this end, here we studied the local foreign body response (FBR) to sustained subdermal delivery of three forms of TAF, namely TAF free base (TAFfb), TAF fumarate salt (TAFfs), and TAFfb with urocanic acid (TAF-UA). Sustained constant drug release was achieved via titanium-silicon carbide nanofluidic implants previously shown to be bioinert. The analysis was conducted in both Sprague-Dawley (SD) rats and rhesus macaques over 1.5 and 3months, respectively. While visual observation did not reveal abnormal adverse tissue reaction at the implantation site, histopathology and Imaging Mass Cytometry (IMC) analyses exposed a local chronic inflammatory response to TAF. In rats, UA mitigated foreign body response to TAF in a concentration-dependent manner. This was not observed in macaques where TAFfb was better tolerated than TAFfs and TAF-UA. Notably, the level of FBR was tightly correlated with local TAF tissue concentration. Further, regardless of the degree of FBR, the fibrotic capsule (FC) surrounding the implants did not interfere with drug diffusion and systemic delivery, as evidenced by TAF PK results and fluorescence recovery after photobleaching (FRAP).

Nanoparticle based intranasal drug delivery system of some herbal medicinal plants for Alzheimer’s disease

AbstractBackgroundDiseases of the Central Nervous System (CNS) such as epilepsy, schizophrenia, meningitis, migraine, Parkinson’s disease and Alzheimer’s disease require delivery of the drug to the brain for effective treatment but it remains problematic area to deal with, as the central nervous system (CNS) is isolated from the whole body by the blood–brain barrier (BBB). This tight physiological barrier limits the drug diffusion towards the brain parenchyma and is considered as the bottleneck in brain drug development. Now this can be circumvented by intraventricular or intracerebral administration. Intra Nasal delivery thus attributes to non‐invasive, essentially painless, high vascularity and the permeability of the nasal mucosa, which aids the drug in bypassing the aforementioned processes of degradation. Now the increasing realization of the side effects of allopathic medicines, coupled with the growing awareness about the medicinal benefits as well as therapeutic effect of herbal products is pushing up the demand for herbal extracts and herbal‐based supplements worldwide.MethodIn this study we designed a natural compound based Nanoformulations for drug delivery via nasal route to treat Alzheimer’s conditionResultAfter various preliminary studies we prepared standard extract loaded Nanoformulations with their particle size between the range 80 – 290nm and sustained release kinetics profile. Further, the toxicity analysis (morphological, cell viability, cytotoxicity assays) of these nanoformulations was performed on RPMI2650 (Human nasal septum) and NB41A3 (Mouse hippocampus) cell lines based on the route and site of drug delivery. Lastly, in vivo experiments were performed with AD (cognitive impairment) induced mice model. There was seemingly, a significant decrease in anti ß amyloid antibody positive neurons in case of optimised nanoformulations in comparison to the galantamine. It was also found to have reduced lesions caused due to the amyloid aggregation reflecting a noted improvement in dispersing and reducing the lesions in the hippocampal tissues.ConclusionIn conclusion, the present study demonstrates that the developed nanoformulations have potential therapeutic effects on improving the pathological state of AD, and might be taken further as a promising candidate for clinical research to evaluate its efficacy in humans.

An injectable liposome-anchored teriparatide incorporated gallic acid-grafted gelatin hydrogel for osteoarthritis treatment

Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1–34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1–34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1β-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.

Design and evaluation of a skin-on-a-chip pumpless microfluidic device

The development of microfluidic culture technology facilitates the progress of study of cell and tissue biology. This technology expands the understanding of pathological and physiological changes. A skin chip, as in vitro model, consisting of normal skin tissue with epidermis and dermis layer (full thickness) was developed. Polydimethylsiloxane microchannels with a fed-batched controlled perfusion feeding system were used to create a full-thick ex-vivo human skin on-chip model. The design of a novel skin-on-a-chip model was reported, in which the microchannel structures mimic the architecture of the realistic vascular network as nutrients transporter to the skin layers. Viabilities of full-thick skin samples cultured on the microbioreactor and traditional tissue culture plate revealed that a precise controlled condition provided by the microfluidic enhanced tissue viability at least for seven days. Several advantages in skin sample features under micro-scale-controlled conditions were found such as skin mechanical strength, water adsorption, skin morphology, gene expression, and biopsy longevity. This model can provide an in vitro environment for localizing drug delivery and transdermal drug diffusion studies. The skin on the chip can be a valuable in vitro model for representing the interaction between drugs and skin tissue and a realistic platform for evaluating skin reaction to pharmaceutical materials and cosmetic products.

Para-Methoxybenzylidene Acetal-Protected D-Glucosamine Derivatives as pH-Responsive Gelators and Their Applications for Drug Delivery.

Carbohydrate-based low molecular weight gelators (LMWGs) are compounds with the capability to self-assemble into complex molecular networks within a solvent, leading to solvent immobilization. This process of gel formation depends on noncovalent interactions, including Van der Waals, hydrogen bonding, and π-π stacking. Due to their potential applications in environmental remediation, drug delivery, and tissue engineering, these molecules have emerged as an important area of research. In particular, various 4,6-O-benzylidene acetal-protected D-glucosamine derivatives have shown promising gelation abilities. In this study, a series of C-2-carbamate derivatives containing a para-methoxy benzylidene acetal functional group were synthesized and characterized. These compounds exhibited good gelation properties in several organic solvents and aqueous mixtures. Upon removal of the acetal functional group under acidic conditions, a number of deprotected free sugar derivatives were also synthesized. Analysis of these free sugar derivatives revealed two compounds were hydrogelators while their precursors did not form hydrogels. For those protected carbamates that are hydrogelators, removal of the 4,6-protection will result in a more water-soluble compound that produces a transition from gel to solution. Given the ability of these compounds to form gels from solution or solution from gels in situ in response to acidic environments, these compounds may have practical applications as stimuli-responsive gelators in an aqueous medium. In turn, one hydrogelator was studied for the encapsulation and release of naproxen and chloroquine. The hydrogel exhibited sustained drug release over a period of several days, with the release of chloroquine being faster at lower pH due to the acid lability of the gelator molecule. The synthesis, characterization, gelation properties, and studies on drug diffusion are discussed.

Influence of Polyvinylpyrrolidone Molecular Weight and Concentration on the Precipitation Inhibition of Supersaturated Solutions of Poorly Soluble Drugs.

Supersaturating drug delivery systems such as solid dispersions of a drug in a polymer are frequently used in pharmaceutical development to enable oral delivery of poorly soluble drugs. In this study, the influence of the concentration and molecular weight of polyvinylpyrrolidone (PVP) on the precipitation inhibition of the poorly soluble drugs albendazole, ketoconazole and tadalafil is investigated to expand the understanding of the mechanism of PVP as a polymeric precipitation inhibitor. A three-level full-factorial design was used to delineate the influence of polymer concentration and viscosity of the dissolution medium on precipitation inhibition. Solutions of PVP K15, K30, K60 or K120 at concentrations of 0.1, 0.5 and 1% (w/v), as well as isoviscous solutions of PVP of increasing molecular weight, were prepared. Supersaturation of the three model drugs was induced by the use of a solvent-shift method. Precipitation of the three model drugs from supersaturated solutions in the absence and presence of polymer was investigated by the use of a solvent-shift method. Time-concentration profiles of the respective drugs in the absence and presence of polymer pre-dissolved in the dissolution medium were obtained by the use of a μDISS Profiler™ to determine the onset of nucleation and the precipitation rate. Multiple linear regression was used to evaluate the hypothesis that precipitation inhibition is influenced by the PVP concentration (i.e., the number of repeat units of the polymer) and the medium viscosity of the polymer for the three model drugs. This study showed that an increased concentration of PVP (i.e., an increased concentration of the PVP repeat units, independent of the molecular weight of the polymer) in solution increased the onset of nucleation and decreased the precipitation rate of the respective drugs during supersaturation, which can be explained by an increase in molecular interactions between the drug and polymer with increasing concentrations of polymer. In contrast, the medium viscosity had no significant influence on the onset of the nucleation and precipitation rate of the drugs, which can be explained by solution viscosity having a negligible effect on the rate of drug diffusion from bulk solution to the crystal nuclei. In conclusion, the precipitation inhibition of the respective drugs is influenced by the concentration of PVP, i.e., by molecular interactions between the drug and polymer. In contrast, the molecular mobility of the drug in solution, i.e., the medium viscosity, has no influence on the precipitation inhibition of the drugs.

Coaxial microfluidic spinning design produced high strength alginate membranes for antibacterial activity and drug release

Directional drug delivery and sufficient strength are two conditions that need to be met for wound dressing. In this paper, an oriented fibrous alginate membrane with sufficient strength was constructed via coaxial microfluidic spinning, and zeolitic imidazolate framework-8/ascorbic acid was used to realize drug delivery and antibacterial activity. The effects of the process parameters of the coaxial microfluidic spinning on the mechanical properties of the alginate membrane were discussed. In addition, it was found that the antimicrobial activity mechanism of zeolitic imidazolate framework-8 was attributed to the disruptive effect of reactive oxygen species (ROS) on bacteria, and the quantitative amount of generated ROS were evaluated by detecting •OH and H2O2. Furthermore, a mathematical drug diffusion model was established and showed high consistency with the experimental data (R2 = 0.99). This study provides a new idea for the preparation of dressing materials with high strength and directional drug delivery and also provides some guidance for the development of coaxial microfluidic spin technology to be used in functional materials for drug release.

Micro Injection Molding of Drug-Loaded Round Window Niche Implants for an Animal Model Using 3D-Printed Molds.

A novel approach for the long-term medical treatment of the inner ear is the diffusion of drugs through the round window membrane from a patient-individualized, drug-eluting implant, which is inserted in the middle ear. In this study, drug-loaded (10 wt% Dexamethasone) guinea pig round window niche implants (GP-RNIs, ~1.30 mm × 0.95 mm × 0.60 mm) were manufactured with high precision via micro injection molding (µIM, Tmold = 160 °C, crosslinking time of 120 s). Each implant has a handle (~3.00 mm × 1.00 mm × 0.30 mm) that can be used to hold the implant. A medical-grade silicone elastomer was used as implant material. Molds for µIM were 3D printed from a commercially available resin (TG = 84 °C) via a high-resolution DLP process (xy resolution of 32 µm, z resolution of 10 µm, 3D printing time of about 6 h). Drug release, biocompatibility, and bioefficacy of the GP-RNIs were investigated in vitro. GP-RNIs could be successfully produced. The wear of the molds due to thermal stress was observed. However, the molds are suitable for single use in the µIM process. About 10% of the drug load (8.2 ± 0.6 µg) was released after 6 weeks (medium: isotonic saline). The implants showed high biocompatibility over 28 days (lowest cell viability ~80%). Moreover, we found anti-inflammatory effects over 28 days in a TNF-α-reduction test. These results are promising for the development of long-term drug-releasing implants for human inner ear therapy.

The Successful Launch and Diffusion of New Therapies

The successful launch and diffusion of new drugs is an essential factor for the survival of many pharmaceutical firms. To ensure the success of a new drug, sophisticated managers in this industry require decision-support tools. This review presents an overview of such strategic and analytical tools, based on significant contributions by marketing scientists. The review is organized according to the components of a launch and diffusion decision chain which represents the sequence of decisions that must be made when launching a new drug. This includes methods for gauging the commercial potential of a new treatment over time, pricing and promotion strategies to maximize value, and leveraging potential across different countries. This review provides an overview of current methods and possible directions for future advances in the field. The successful launch and diffusion of new therapies are key factors in the success of pharmaceutical firms. To ensure the success of a new drug, sophisticated managers in this industry require decision-support tools. This review provides an overview of such strategic and analytical tools, based on significant contributions by marketing scientists. This includes methods for gauging the commercial potential of a new treatment over time, pricing and promotion strategies to maximize value, and leveraging potential across different countries. This review is organized according to the components of a launch and diffusion decision chain, which covers the essential decisions to be made when launching a new drug.

Theoretical and Experimental Aspects of Sodium Diclofenac Salt Release from Chitosan-Based Hydrogels and Possible Applications.

Two formulations based on diclofenac sodium salt encapsulated into a chitosan hydrogel were designed and prepared, and their drug release was investigated by combining in vitro results with mathematical modeling. To understand how the pattern of drug encapsulation impacted its release, the formulations were supramolecularly and morphologically characterized by scanning electron microscopy and polarized light microscopy, respectively. The mechanism of diclofenac release was assessed by using a mathematical model based on the multifractal theory of motion. Various drug-delivery mechanisms, such as Fickian- and non-Fickian-type diffusion, were shown to be fundamental mechanisms. More precisely, in a case of multifractal one-dimensional drug diffusion in a controlled-release polymer-drug system (i.e., in the form of a plane with a certain thickness), a solution that allowed the model's validation through the obtained experimental data was established. The present research reveals possible new perspectives, for example in the prevention of intrauterine adhesions occurring through endometrial inflammation and other pathologies with an inflammatory mechanism background, such as periodontal diseases, and also therapeutic potential beyond the anti-inflammatory action of diclofenac as an anticancer agent, with a role in cell cycle regulation and apoptosis, using this type of drug-delivery system.

Novel Hydrate and Anhydrate Cocrystals/Salts of Norfloxacin and Their Physicochemical Properties

The low solubility and low permeability of Biopharmaceutics Classification System BCS class IV antibiotic drug norfloxacin (NORF) were studied for improvement of physicochemical properties in hydrated and anhydrous cocrystals/salts of NORF with methyl paraben (MBZ), ethyl paraben, methanesulfonic acid (MSA), benzenesulfonic acid (BSA), p-toluenesulfonic acid (PTSA), and tyramine (TYM). These crystalline forms were characterized by powder X-ray diffraction (PXRD), thermal [differential scanning calorimetry (DSC)], gravimetric [thermogravimetric analysis (TGA)], spectroscopic [infrared (IR)], and microscopy [scanning electron microscopy (SEM)] techniques. The crystal structures of NORF-MBZ-HYD, NORF-MSA-HYD, NORF-PTSA, and NORF-TYM-HYD were analyzed by single-crystal X-ray diffraction. Further, the hydrated and anhydrous forms were characterized by IR, DSC, and TGA to understand the hydration and dehydration events and by field emission SEM for crystal morphology and shape/size characteristics. Solubility, dissolution, and diffusion measurements showed that NORF anhydrous forms are more soluble and diffusible than their corresponding hydrated forms. Notably, NORF ionic crystal forms with MSA and BSA are highly soluble with good dissolution rates and high cumulative drug diffusion.

Release kinetics and binding interactions of curcumin‐encapsulated nanoparticles released from chitosan‐graft‐(methoxy poly(ethylene glycol)‐block‐polycaprolactone) injectable hydrogels

AbstractInjectable hydrogels are alternative materials for drug delivery in biomedical applications. Most injectable hydrogels are derived from stimuli‐responsive polymers that can respond to the changes of physical and/or chemical properties of the environment, such as temperature and pH variation. In this study, chitosan‐graft‐(methoxy poly (ethylene glycol)‐block‐polycaprolactone) injectable hydrogels were loaded with curcumin in different concentrations. The loading capacity and encapsulation efficiency of curcumin in such hydrogels were increased and decreased respectively with increasing curcumin concentrations. The encapsulation efficiency, however, was more than 90% for all formulations. Such hydrogels demonstrated curcumin release that proceeded in a sustained manner. The release profiles followed Korsmeyer‐Peppas and zero‐order kinetic release models which suggested that the release was facilitated by drug diffusion and the erosion of the self‐assembled polymeric networks. The curcumin released from the hydrogels was found as encapsulated core‐shell nanoparticles, the size of which depended on the loading concentration. A combination of fluorescence spectroscopy and thermodynamics analysis showed that van der Waals interactions and hydrogen bonds were major binding forces between curcumin and the copolymers. In addition, the curcumin‐encapsulated nanoparticles showed a progressive reduction in survival of the cervical cancer HeLa cell line, as shown in in vitro cytotoxicity experiments. © 2023 Society of Industrial Chemistry.

Engineering and Development of a Tissue Model for the Evaluation of Microneedle Penetration Ability, Drug Diffusion, Photothermal Activity, and Ultrasound Imaging: A Promising Surrogate to Ex Vivo and In Vivo Tissues (Adv. Mater. 18/2023)

Tissue Models In article number 2210034, Pooyan Makvandi, Virgilio Mattoli, and co-workers report the fabrication of tissue substitutes for ex vivo human tissues and animals. Tissue models based on hydrogel/silicon films are prepared for different applications in the biomedical sector. These customized tissue surrogates can be employed as a platform to evaluate the ability of microneedle insertion, diffusion of drugs, activity of photothermal agents, and the performance of ultrasound bioimaging.

Design and simulation analysis of electric needleless syringe

A new design of a needleless syringe based on a moving-coil electromagnetic linear actuator drive is proposed to address the problems of the uncontrollable driving force and bulky structure commonly found in current commercial needleless syringes. The structural parameters of the moving-coil electromagnetic linear actuator with the electromagnetic driving force at different current strengths are obtained using the finite element analysis method. The results of jet stagnation pressure and jet velocity were obtained by MATLAB numerical calculation and CFD jet simulation. The process of 0.1 ml drug diffusion under the skin at a current size of 40 A was simulated. The results show that the jet stagnation pressure at the nozzle is 32 MPa, the jet velocity is 246 m/s, and the jet diffusion depth reaches 15 mm under the maximum driving force condition. The output electromagnetic force of the moving-coil electromagnetic linear actuator in this scheme is proportional to the current’s magnitude, and the actuator’s small size allows it to be used as a driving component of a hand-held needleless syringe.

Development and in vitro assessment of Analgesic and Anti-inflammatory Mefenamic acid Nanosponge Loaded Topical Formulation

The present research work was done with the objective of topical formulation development of poorly water-soluble drug Mefenamic acid. The drug was firstly incorporated in nanosponge of ethyl cellulose. Then Mefenamic acid nanosponge-loaded topical gel formulations were developed by using Carbopol 934 as a gel-forming polymer. The Mefenamic acid-loaded nanosponges were tested for various quality parameters such as particle size distribution, polydispersity.index(PI),. Surface morphology and drug entrapment efficiency etc. Gel formulations were tested for viscosity, pH, in vitro diffusion and other parameters. The average size of developed nanosponge preparations was found between 250nm to 894nm. Scanning electron microscopy photographs of developed formulations clearly reveal the spongy and porous nature of particles along with spherical shape. The PI was. found in. the range. of 0.206 to 0.934. It was found that formulation N3 with a drug-to-polymer ratio of 1:4 has the highest drug loading. Further nanosponge were characterized for different parameters and results revealed acceptable characteristics of N3 formulation. These prepared nanosponges were loaded in topical Carbopol gel (Formulation G3) and evaluated for in vitro diffusion release. Obtained in vitro data was applied to numerous kinetic models which reveal typical zero order in vitro drug diffusion with prolonged release of Mefenamic acid and therefore it can be effectively used as analgesic and anti-inflammatory formulation.

Fabrication of acacia gum grafted copolymeric network hydrogel for biomedical applications

Keeping in view therapeutic role of gum polysaccharides and to explore advancements in research expectancy in area of gum for future research for development of new materials for biomedical applications, in present research, acacia gum was grafted with poly(acrylamide) [poly(AAm)] and poly(2-arylamido-2-methylpropanesulfonic acid) poly(AMPSA) to design hydrogels by copolymerization for use in drug delivery of levofloxacin antibiotic drug. These co-polymers were characterized by SEMs, AFM, FTIR, 13C NMR, XRD and TGA. The SEM indicated uneven surface due to grafting and AFM confirmed the surface roughness for better mucoadhesion. The prominent peaks at 178.871 ppm and 52.180 ppm indicated the incorporation of the AAM and AMPSA due to CO and C–S into copolymer by grafting reaction. XRD indicated the amorphous region and TGA reflected three stages thermal decomposition. The results reflected slow release of drug due to supra-molecular interactions between drug and copolymers and diffusion of drug occurred with non-Fickian mechanism from network hydrogels with first order kinetic release model. The copolymeric material showed radical scavenging activity was 26.12 ± 2.23% in DPPH assay and 3.42 ± 0.396% hemolytic index values. The network copolymers also showed 0.281 ± 0.093 N peak detachment force from mucoadhesive test. The results of biomedical assay inference the non-hemolytic behavior with antioxidant and mucoadhesive nature of the network copolymers. These results signified the suitability of the polymeric materials for colon specific drug delivery.

Combined intramyocardial injectable hydrogel and pericardial adhesive hydrogel patch therapy strategy to achieve gene/ion/gas delivery for improving cardiac function

Circular RNA (circRNA), bioactive ion and nitric oxide (NO) are beneficial to myocardial repair after myocardial infarction (MI); however, to achieve efficient intervention of circRNA and delivery of NO and ion throughout myocardium still remains difficult. Injectable hydrogels have been frequently used to release angiogenic factors; however, due to the limited drug diffusion distance, angiogenic factors are difficult to reach the epicardium – a viable target for angiogenesis. Herein, a combined strategy based on coadministration of lipo/pcircRNA and strontium ions-containing nanoparticles-encapsulated injectable hydrogel and NO-bearing liposome-loaded pericardial adhesive hydrogel patch is proposed to realize intramyocardial gene/ion delivery and epicardial NO delivery to inhibit cardiomyocyte apoptosis and inflammatory response, and circumvent insufficient angiogenesis problem. The hydrogel prepared via Schiff-reaction of hydrazide-hyaluronic acid and aldehydated-laminarin with self-immunoregulation function is injected into the myocardium to deliver lipo/pcircRNA nanoparticles and strontium ions to inhibit cardiomyocyte apoptosis and partially promote angiogenesis. To further boost angiogenesis, an adhesive hyaluronic acid-based hydrogel is bonded to the myocardial surface by pre-anchored sponge that can remove hydration layer, to achieve the release of NO nanodrug in epicardium. This combination therapy contributes to a significant inhibition of cardiomyocyte apoptosis and inflammatory response and maximum angiogenesis, thus improving cardiac function.

Drug Diffusion from the Gastrointestinal Tract through the Body, Bloodstream, and Urinary Compartments: Mathematical Modeling Approach

This research involved the formulation of a mathematical system that mimics the diffusion of drug concentration from the gastrointestinal tract to the body and bloodstream compartments and the elimination through the urinary tract. The models are formulated separately as ordinary differential equations for the aforementioned compartments, where some pertinent entry parameters in the form of rates were obtained. We applied the Laplace method of solution to solve the formulated mathematical models for the drug concentration in the various compartments as mentioned. In order to investigate the effect of the drug concentration in the urinary and gastrointestinal tracts on the concentration in the body and bloodstream compartments, we solved the urinary tract and gastrointestinal models and substituted the results into the models representing the drug concentration in the body and bloodstream compartments, and those models were later solved to obtain the function representing the body and bloodstream compartments. The research further involved the numerical simulation of the various functions obtained by varying the various rates of diffusion on the drug concentration in the body and bloodstream compartments. The results revealed that the various diffusion rate changes affect the drug concentration level in the body and bloodstream compartments, respectively. The novelty of this research is the fact that we’ve been able to incorporate drug administration and concretion in the gastrointestinal and urinary tracts, which were not considered previously. This research is recommended for application by mathematicians and scientists alike who could be interested in understanding drug diffusion from one compartment to another with different rate constants.