scholarly journals Modeling programmable drug delivery in bioelectronics with electrochemical actuation

2021 ◽  
Vol 118 (11) ◽  
pp. e2026405118
Author(s):  
Raudel Avila ◽  
Chenhang Li ◽  
Yeguang Xue ◽  
John A. Rogers ◽  
Yonggang Huang
Keyword(s):  
Drug Delivery ◽  
Analytical Model ◽  
System Optimization ◽  
Delivery Time ◽  
In Vivo Experiments ◽  
Missing Variables ◽  
The Many ◽  
Variable Influence ◽  
Electrochemical Actuation

Drug delivery systems featuring electrochemical actuation represent an emerging class of biomedical technology with programmable volume/flowrate capabilities for localized delivery. Recent work establishes applications in neuroscience experiments involving small animals in the context of pharmacological response. However, for programmable delivery, the available flowrate control and delivery time models fail to consider key variables of the drug delivery system––microfluidic resistance and membrane stiffness. Here we establish an analytical model that accounts for the missing variables and provides a scalable understanding of each variable influence in the physics of delivery process (i.e., maximum flowrate, delivery time). This analytical model accounts for the key parameters––initial environmental pressure, initial volume, microfluidic resistance, flexible membrane, current, and temperature––to control the delivery and bypasses numerical simulations allowing faster system optimization for different in vivo experiments. We show that the delivery process is controlled by three nondimensional parameters, and the volume/flowrate results from the proposed analytical model agree with the numerical results and experiments. These results have relevance to the many emerging applications of programmable delivery in clinical studies within the neuroscience and broader biomedical communities.

scholarly journals Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2920
Author(s):  
Ameeduzzafar Zafar ◽  
Syed Sarim Imam ◽  
Nabil K. Alruwaili ◽  
Omar Awad Alsaidan ◽  
Mohammed H. Elkomy ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Oral Delivery ◽  
Ex Vivo ◽  
In Vitro Release ◽  
System Optimization ◽  
Globule Size

Hypertension is a cardiovascular disease that needs long-term medication. Oral delivery is the most common route for the administration of drugs. The present research is to develop piperine self-nanoemulsifying drug delivery system (PE-SNEDDS) using glyceryl monolinoleate (GML), poloxamer 188, and transcutol HP as oil, surfactant, and co-surfactant, respectively. The formulation was optimized by three-factor, three-level Box-Behnken design. PE-SNEDDs were characterized for globule size, emulsification time, stability, in-vitro release, and ex-vivo intestinal permeation study. The optimized PE-SNEDDS (OF3) showed the globule size of 70.34 ± 3.27 nm, percentage transmittance of 99.02 ± 2.02%, and emulsification time of 53 ± 2 s Finally, the formulation OF3 was transformed into solid PE-SNEDDS (S-PE-SNEDDS) using avicel PH-101 as adsorbent. The reconstituted SOF3 showed a globule size of 73.56 ± 3.54 nm, PDI of 0.35 ± 0.03, and zeta potential of −28.12 ± 2.54 mV. SEM image exhibited the PE-SNEDDS completely adsorbed on avicel. Thermal analysis showed the drug was solubilized in oil, surfactant, and co-surfactant. S-PE-SNEDDS formulation showed a more significant (p < 0.05) release (97.87 ± 4.89% in 1 h) than pure PE (27.87 ± 2.65% in 1 h). It also exhibited better antimicrobial activity against S. aureus and P. aeruginosa and antioxidant activity as compared to PE dispersion. The in vivo activity in rats exhibited better (p < 0.05) antihypertensive activity as well as 4.92-fold higher relative bioavailability than pure PE dispersion. Finally, from the results it can be concluded that S-PE-SNEDDS might be a better approach for the oral delivery to improve the absorption and therapeutic activity.

scholarly journals Biodegradable Micelles for NIR/GSH-Triggered Chemophototherapy of Cancer

Nanomaterials ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 91 ◽  
Author(s):  
Chuan Zhang ◽  
Yuzhuo Wang ◽  
Yue Zhao ◽  
Hou Liu ◽  
Yueqi Zhao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Near Infrared ◽  
Mixed Micelles ◽  
Infrared Light ◽  
Stimuli Responsive ◽  
High Concentration ◽  
Chemotherapy Drugs ◽  
In Vivo Experiments ◽  
Low Efficiency

The chemotherapy of stimuli-responsive drug delivery systems (SDDSs) is a promising method to enhance cancer treatment effects. However, the low efficiency of chemotherapy drugs and poor degradation partly limit the application of SDDSs. Herein, we report doxorubicin (DOX)-loading mixed micelles for biotin-targeting drug delivery and enhanced photothermal/photodynamic therapy (PTT/PDT). Glutathione (GSH)-responsive mixed micelles were prepared by a dialysis method, proportionally mixing polycaprolactone-disulfide bond-biodegradable photoluminescent polymer (PCL-SS-BPLP) and biotin-polyethylene glycol-cypate (biotin-PEG-cypate). Chemically linking cypate into the mixed micelles greatly improved cypate solubility and PTT/PDT effect. The micelles also exhibited good monodispersity and stability in cell medium (~119.7 nm), low critical micelles concentration, good biodegradation, and photodecomposition. The high concentration of GSH in cancer cells and near-infrared light (NIR)-mediated cypate decomposition were able to achieve DOX centralized release. Meanwhile, the DOX-based chemotherapy combined with cypate-based NIR-triggered hyperthermia and reactive oxygen species could synergistically induce HepG2 cell death and apoptosis. The in vivo experiments confirmed that the micelles generated hyperthermia and achieved a desirable therapeutic effect. Therefore, the designed biodegradable micelles are promising safe nanovehicles for antitumor drug delivery and chemo/PTT/PDT combination therapy.

scholarly journals A Concise Review of Nanomaterials for Drug Delivery and Release

2020 ◽  
Vol 16 (3) ◽  
pp. 399-412
Author(s):  
Alfonso Toro-Córdova ◽  
Beatriz Sanz ◽  
Gerardo F. Goya
Keyword(s):  
Drug Delivery ◽  
Polymeric Nanoparticles ◽  
Contextual Information ◽  
Specific Area ◽  
General View ◽  
Clinical Phase ◽  
In Vivo Experiments ◽  
Recent Developments

This review provides an updated vision about the recent developments in the field of drug vectorization using functional nanoparticles and other nanovectors. From a large number of these nanotechnology-based drug delivery systems that emerge nearly every week, only a tiny fraction reaches a pre-clinical or clinical phase study. In this report, we intend to provide contextual information about those nanocarriers and release methods that have shown the best outcomes at in vitro and in vivo experiments, highlighting those with proven therapeutic efficiency in humans. From silicabased porous nanoparticles to liposomes or polymeric nanoparticles, each one of these nanosystems has its advantages and drawbacks. We describe and discuss briefly those approaches that, in our criterion, have provided significant advancements over existing therapies at the in vivo level. This work also provides a general view of those commercially available nanovectors and their specific area of therapeutic action.

scholarly journals In Silico Model as a Tool for Interpretation of Intestinal Infection Studies

2006 ◽  
Vol 73 (2) ◽  
pp. 508-515 ◽  
Author(s):  
Peter de Jong ◽  
Marc M. M. Vissers ◽  
Roelof van der Meer ◽  
Ingeborg M. J. Bovee-Oudenhoven
Keyword(s):  
Experimental Data ◽  
Pathogenic Bacteria ◽  
Detrimental Effect ◽  
In Vivo Experiments ◽  
Nutrition Research ◽  
Model Predictions ◽  
Calculation Results ◽  
The Many ◽  
Validation Experiments

ABSTRACT In nutrition research the number of human in vivo experiments is limited because of the many restrictions and the high costs of testing in humans. Up to now predictive computer models aiming to enhance research have been rare or too complex, with many nonmeasurable adjustable parameters. This study aimed to develop a basic physicochemical computer model for a first quantitative interpretation of results obtained from in vivo intestinal experiments with bacteria. This new modeling approach is validated with results obtained from gut infection studies in vivo. The design of the model is described, and its ability to reproduce experimental data is evaluated. The model predictions are compared with new experimental data. The phenomena that take place in the gastrointestinal tract are summarized by model constants for growth, adherence, and release of bacteria. Although the model is far from describing all details and many processes in the intestine are combined, the model calculation results lead to reasonable conclusions and interesting hypotheses. One of these hypotheses concluded from the model outcomes is that Escherichia coli bacteria have a much lower intestinal growth rate in humans than in rats. Extra laboratory validation experiments proved the reliability of this hypothesis predicted by the model. In addition, the known protective effect of dietary calcium and detrimental effect of clindamycin on the growth and adherence of Salmonella bacteria could be quantified. From these results it is clear that the model enhances the interpretation of in vivo gastrointestinal experiments and will facilitate research trajectories towards new functional foods that improve resistance to pathogenic bacteria in humans.

scholarly journals Near-infrared light and tumor microenvironment dual responsive size-switchable nanocapsules for multimodal tumor theranostics

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhiyi Wang ◽  
Yanmin Ju ◽  
Zeeshan Ali ◽  
Hui Yin ◽  
Fugeng Sheng ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Near Infrared ◽  
Infrared Light ◽  
Near Infrared Light ◽  
In Vivo Experiments ◽  
Dual Responsive ◽  
Synthetic Strategy ◽  
Scientific Challenge

Abstract Smart drug delivery systems (SDDSs) for cancer treatment are of considerable interest in the field of theranostics. However, developing SDDSs with early diagnostic capability, enhanced drug delivery and efficient biodegradability still remains a scientific challenge. Herein, we report near-infrared light and tumor microenvironment (TME), dual responsive as well as size-switchable nanocapsules. These nanocapsules are made of a PLGA-polymer matrix coated with Fe/FeO core-shell nanocrystals and co-loaded with chemotherapy drug and photothermal agent. Smartly engineered nanocapsules can not only shrink and decompose into small-sized nanodrugs upon drug release but also can regulate the TME to overproduce reactive oxygen species for enhanced synergistic therapy in tumors. In vivo experiments demonstrate that these nanocapsules can target to tumor sites through fluorescence/magnetic resonance imaging and offer remarkable therapeutic results. Our synthetic strategy provides a platform for next generation smart nanocapsules with enhanced permeability and retention effect, multimodal anticancer theranostics, and biodegradability.

Preparation of Isorhamnetin Nanoparticles and Their Targeting Efficiency to Nasopharynx Cancer

2021 ◽  
Vol 21 (2) ◽  
pp. 1293-1299
Author(s):  
Bo Yang ◽  
Fang Zhang ◽  
Weili Yuan ◽  
Li Du ◽  
Xuejun Jiang
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Water Solubility ◽  
Antibacterial Properties ◽  
In Vivo Experiments ◽  
Cervical Cancer Cells ◽  
Targeted Drug ◽  
Nasopharynx Cancer

Cancer is a serious threat to human health and longevity, and is an important cause of disease death. At present, cancer is mainly treated by surgery, radiotherapy, chemotherapy, etc. The existing various methods of treating tumors have their limitations. Although there are immune, genetic and other treatment methods, they are still immature. Therefore, tumor-targeted drug delivery systems have attracted more and more attention in cancer treatment. Targeted nano-drugs are selectively targeted to the tumor surface to achieve targeted drug delivery. New nano-drugs have created new hotspots in medical research. It could be a new strategy for treating cancer. Carboxymethyl chitosan (CMC) is formed by the carboxylation of chitosan. It has good water solubility and biodegradability, biocompatibility and antibacterial properties, so CMC is the best choice as a nanomaterial. Isorhamnetin (Iso) is an important anticancer drug. This article uses nanomedicine technology to construct CMC as a carrier, Iso as an antitumor drug, and using polydopamine (PDA) to modify the surface of the particles. Through in vitro and in vivo experiments, the Iso/CMC-PDA nanosphere Targeting and Growth Inhibition of Cervical Cancer Cells.

scholarly journals Moxifloxacin releasing intraocular implant based on a cross-linked hyaluronic acid membrane

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Ju Kim ◽  
Mi-Young Jung ◽  
Joo-Hee Park ◽  
Ha-Jin Pak ◽  
Martha Kim ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Hyaluronic Acid ◽  
Bacterial Infections ◽  
Eye Drops ◽  
Ophthalmic Surgery ◽  
In Vivo Experiments ◽  
Conventional Drug ◽  
Intraocular Implant ◽  
Intraocular Drug Delivery

AbstractIntraocular antibiotic delivery is an important technique to prevent bacterial infection after ophthalmic surgery, such as cataract surgery. Conventional drug delivery methods, such as antibiotic eye drops, have limitations for intraocular drug delivery due to the intrinsic barrier effect of the cornea. Therefore, frequent instillation of antibiotic eyedrops is necessary to reach a sufficient bactericidal concentration inside the eye. In this study, an intraocular implant, MXF-HA, that combines hyaluronic acid (HA) and moxifloxacin (MXF) was developed to increase the efficiency of intraocular drug delivery after surgery. MXF-HA is manufactured as a thin, transparent, yellow-tinted membrane. When inserted into the eye in a dry state, MXF-HA is naturally hydrated and settles in the eye, and the MXF contained therein is delivered by hydrolysis of the polymer over time. It was confirmed through in vivo experiments that MXF delivery was maintained in the anterior chamber of the eye at a concentration sufficient to inhibit Pseudomonas aeruginosa and Staphylococcus aureus for more than 5 days after implantation. These results suggest that MXF-HA can be utilized as a potential drug delivery method for the prevention and treatment of bacterial infections after ophthalmic surgery.

Nanoparticulate drug-delivery systems for fighting microbial biofilms: from bench to bedside

2020 ◽  
Vol 15 (8) ◽  
pp. 679-698 ◽  
Author(s):  
Gratiela G Pircalabioru ◽  
Mariana-Carmen Chifiriuc
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Antimicrobial Agents ◽  
Delivery Systems ◽  
In Vivo Studies ◽  
Microbial Biofilms ◽  
Adverse Environmental Conditions ◽  
The Many

Biofilms are highly tolerant to antimicrobial agents and adverse environmental conditions being important reservoirs for chronic and hard-to-treat infections. Nanomaterials exhibit microbiostatic/microbicidal/antipathogenic properties and can be also used for the delivery of antibiofilm agents. However, few of the many promising leads offered by nanotechnology reach clinical studies and eventually, become available to clinicians. The aim of this paper was to review the progress and challenges in the development of nanotechnology-based antibiofilm drug-delivery systems. The main identified challenges are: most papers report only in vitro studies of the activity of different nanoformulations; lack of standardization in the methodological approaches; insufficient collaboration between material science specialists and clinicians; paucity of in vivo studies to test efficiency and safety.

Development of a multifunctional gold nanoplatform for combined chemo-photothermal therapy against oral cancer

Nanomedicine ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. 661-676 ◽  
Author(s):  
Zengying Liu ◽  
Jianbo Shi ◽  
Bangshang Zhu ◽  
Qin Xu
Keyword(s):  
Drug Delivery ◽  
Oral Cancer ◽  
Photothermal Therapy ◽  
Drug Loading ◽  
Antitumor Efficacy ◽  
Antitumor Effects ◽  
In Vivo Experiments ◽  
Low Toxicity

Aim: To design and fabricate a multifunctional drug-delivery nanoplatform for oral cancer therapy. Materials & methods: Polyethylene glycol-stabilized, PDPN antibody (PDPN Ab)- and doxorubicin (DOX)-conjugated gold nanoparticles (AuNPs) were prepared and evaluated for their cytotoxicity and antitumor efficacy in both chemotherapy and photothermal therapy. Results: The obtained (PDPN Ab)-AuNP-DOX system presents low toxicity, a high drug loading capacity and cellular uptake efficiency. Both in vitro and in vivo experiments demonstrate that (PDPN Ab)-AuNP-DOX has enhanced antitumor efficacy. Treatment with (PDPN Ab)-AuNP-DOX combined with laser irradiation exhibits superior antitumor effects. Conclusion: This (PDPN Ab)-AuNP-DOX system may be used as a versatile drug-delivery nanoplatform for targeted and combined chemo-photothermal therapy against oral cancer.

Oral Drug Delivery Systems for Ulcerative Colitis Therapy: A Comparative Study with Microparticles and Nanoparticles

2019 ◽  
Vol 19 (4) ◽  
pp. 304-311 ◽  
Author(s):  
Panpan Ma ◽  
Xiaoying Si ◽  
Qiubing Chen ◽  
Lijun Ma ◽  
Meili Hou ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Drug Delivery ◽  
Oral Drug Delivery ◽  
Oral Drug ◽  
Average Particle ◽  
Oil Emulsion ◽  
In Vivo Experiments ◽  
Therapeutic Outcomes ◽  
Evaporation Technique

Background: Oral administrations of microparticles (MPs) and nanoparticles (NPs) have been widely employed as therapeutic approaches for the treatment of ulcerative colitis (UC). However, no previous study has comparatively investigated the therapeutic efficacies of MPs and NPs. Methods: In this study, curcumin (CUR)-loaded MPs (CUR-MPs) and CUR-loaded NPs (CUR-NPs) were prepared using a single water-in-oil emulsion solvent evaporation technique. Their therapeutic outcomes against UC were further comparatively studied. Results: The resultant spherical MPs and NPs exhibited slightly negative zeta-potential with average particle diameters of approximately 1.7 &#181;m and 270 nm, respectively. It was found that NPs exhibited a much higher CUR release rate than MPs within the same period of investigation. In vivo experiments demonstrated that oral administration of CUR-MPs and CUR-NPs reduced the symptoms of inflammation in a UC mouse model induced by dextran sulfate sodium. Importantly, CUR-NPs showed much better therapeutic outcomes in alleviating UC compared with CUR-MPs. Conclusion: NPs can improve the anti-inflammatory activity of CUR by enhancing the drug release and cellular uptake efficiency, in comparison with MPs. Thus, they could be exploited as a promising oral drug delivery system for effective UC treatment.

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