scholarly journals LMD-01. Quantifying intrathecal drug delivery utilizing programmable ventriculoperitoneal shunts

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii7-iii7
Author(s):  
Sheila McThenia ◽  
Neeta Pandit-Taskar ◽  
Milan Grkovski ◽  
Maria Donzelli ◽  
Safiatu Diagana ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cellular Therapy ◽  
Drug Distribution ◽  
Cancer Center ◽  
Csf Flow ◽  
Ventriculoperitoneal Shunts ◽  
Drug Activity ◽  
Patients Âgés ◽  
Drug Concentrations ◽  
Intraventricular Chemotherapy

Abstract Background Programmable ventriculoperitoneal shunts (pVP shunts) are increasingly utilized for intraventricular chemotherapy, radioimmunotherapy, and/or cellular therapy. Shunt adjustments allow optimization of thecal space drug concentrations with minimization in the peritoneum. Drug delivery quantification using several types of pVP shunts has not been reported. Methods We performed a retrospective analysis on patients with CNS tumors and pVP shunts at Memorial Sloan Kettering Cancer Center from 2003–2020, noting shunt model. CSF flow through the pVP shunt was evaluated using In-111-DTPA scintigraphy at approximately 4 and 24 hours after injection. pVP shunts were calibrated pre-injection to minimize peritoneal flow and re-calibrated to baseline setting 4–5 hours following injection. Scintigraphy studies quantified ventricular-thecal and peritoneal drug activity at these 2 time points. Results Twenty-one CSF flow studies were administered to 15 patients, ages 1–27 years. Diagnoses included medulloblastoma (N=10), metastatic neuroblastoma (N=3), pineoblastoma (N=1), and choroid plexus carcinoma (N=1). Models of pVP shunts included Aesculap Miethke proGAV (N=3), Aesculap Miethke proGAV2.0 (N=3), Codman HAKIM (N=2), Codman Certas Plus (N=1), Medtronic STRATA (N= 5), and Sophysa Polaris (N= 1). All 21 studies (100%) demonstrated ventriculo-thecal drug activity. 29% (6 of 21) of the studies had no peritoneal uptake visible by imaging. 73% (16 of 21) of the studies had minimal peritoneal uptake (<12%), and 24% (5 of 21) demonstrated moderate peritoneal uptake (12–37%). Models of pVP shunts measuring minimal to no peritoneal uptake included: Aesculap Miethke proGAV (N=2), Aesculap Miethke proGAV2.0 (N=3), Codman HAKIM (N=2), Codman Certas Plus (N=1), Medtronic STRATA (N= 3), and Sophysa Polaris (N= 1). Conclusions pVP shunts successfully deliver drugs to the ventriculo-thecal space with 80% of studies having minimal (<12%) peritoneal drug activity. Though efficacy varies by shunt model, low numbers preclude conclusions regarding model superiority. CSF flow scintigraphy studies reliably assess drug distribution.

scholarly journals IMMU-15. QUANTIFYING INTRATHECAL DRUG DELIVERY UTILIZING PROGRAMMABLE VENTRICULOPERITONEAL SHUNTS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i30-i30
Author(s):  
Sheila McThenia ◽  
Neeta Pandit-Taskar ◽  
Milan Grkovski ◽  
Maria Donzelli ◽  
Safiatu Diagana ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cellular Therapy ◽  
Drug Distribution ◽  
Cancer Center ◽  
Csf Flow ◽  
Drug Activity ◽  
Patients Âgés ◽  
Drug Concentrations ◽  
Intraventricular Chemotherapy ◽  
Flow Through

Abstract Background Programmable ventriculoperitoneal (pVP) shunts are increasingly utilized for intraventricular chemotherapy, radioimmunotherapy, and/or cellular therapy. Shunt adjustments allow optimization of thecal space drug concentrations with minimization in the peritoneum. Drug delivery quantification using several types of pVP shunts has not been reported. Methods We performed a retrospective analysis on patients with CNS tumors and pVP shunts at Memorial Sloan Kettering Cancer Center from 2003–2020, noting shunt model. CSF flow through the pVP shunt was evaluated using In-111-DTPA scintigraphy at approximately 4 hours and 24 hours after injection. pVP shunts were calibrated pre-injection to minimize peritoneal flow and re-calibrated to baseline setting 4–5 hours following injection. Scintigraphy studies quantified ventricular-thecal and peritoneal drug activity at these 2 time points. Results Twenty-one CSF flow studies were administered to 15 patients, ages 1–27 years. Diagnoses included medulloblastoma (N=10), metastatic neuroblastoma (N=3), pineoblastoma (N=1), and choroid plexus carcinoma (N=1). pVP shunt models included Aesculap Miethke proGAV (N=3), Aesculap Miethke proGAV2.0 (N=3), Codman HAKIM (N=2), Codman Certas Plus (N=1), Medtronic STRATA (N= 5), and Sophysa Polaris (N= 1). All 21 studies (100%) demonstrated ventriculo-thecal drug activity. 29% (6 of 21) of the studies had no peritoneal uptake visible by imaging. 73% (16 of 21) of the studies had minimal peritoneal uptake (<12%), and 24% (5 of 21) demonstrated moderate peritoneal uptake (12–37%). pVP shunt models measuring minimal to no peritoneal uptake included: Aesculap Miethke proGAV (N=2), Aesculap Miethke proGAV2.0 (N=3), Codman HAKIM (N=2), Codman Certas Plus (N=1), Medtronic STRATA (N= 3), and Sophysa Polaris (N= 1). Conclusions Successful drug delivery to the ventriculo-thecal space can be accomplished using pVP shunts: 80% of studies have minimal (<12%) peritoneal drug activity. Though efficacy varies by shunt model, low numbers preclude conclusions regarding model superiority. CSF flow scintigraphy studies reliably assess drug distribution.

scholarly journals Modeling and Analysis of Drug-Eluting Stents With Biodegradable PLGA Coating: Consequences on Intravascular Drug Delivery

2014 ◽  
Vol 136 (11) ◽  
Author(s):  
Xiaoxiang Zhu ◽  
Richard D. Braatz
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Arterial Wall ◽  
Drug Distribution ◽  
Integrated Model ◽  
Drug Binding ◽  
Drug Eluting Stents ◽  
Drug Concentrations ◽  
Drug Eluting ◽  
Release Profiles

Increasing interests have been raised toward the potential applications of biodegradable poly(lactic-co-glycolic acid) (PLGA) coatings for drug-eluting stents in order to improve the drug delivery and reduce adverse outcomes in stented arteries in patients. This article presents a mathematical model to describe the integrated processes of drug release in a stent with PLGA coating and subsequent drug delivery, distribution, and drug pharmacokinetics in the arterial wall. The integrated model takes into account the PLGA degradation and erosion, anisotropic drug diffusion in the arterial wall, and reversible drug binding. The model simulations first compare the drug delivery from a biodegradable PLGA coating with that from a biodurable coating, including the drug release profiles in the coating, average arterial drug levels, and arterial drug distribution. Using the model for the PLGA stent coating, the simulations further investigate drug internalization, interstitial fluid flow in the arterial wall, and stent embedment for their impact on drug delivery. Simulation results show that these three factors, while imposing little change in the drug release profiles, can greatly change the average drug concentrations in the arterial wall. In particular, each of the factors leads to significant and yet distinguished alterations in the arterial drug distribution that can potentially influence the treatment outcomes. The detailed integrated model provides insights into the design and evaluation of biodegradable PLGA-coated drug-eluting stents for improved intravascular drug delivery.

scholarly journals Drug Delivery by Ultrasound-Responsive Nanocarriers for Cancer Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1135
Author(s):  
Kristin Entzian ◽  
Achim Aigner
Keyword(s):  
Drug Delivery ◽  
Biological Effects ◽  
Invasive Technique ◽  
Stimuli Responsive ◽  
Comprehensive Overview ◽  
Drug Concentrations ◽  
Therapeutic Outcomes ◽  
Cost Efficient ◽  
Safety Considerations

Conventional cancer chemotherapies often exhibit insufficient therapeutic outcomes and dose-limiting toxicity. Therefore, there is a need for novel therapeutics and formulations with higher efficacy, improved safety, and more favorable toxicological profiles. This has promoted the development of nanomedicines, including systems for drug delivery, but also for imaging and diagnostics. Nanoparticles loaded with drugs can be designed to overcome several biological barriers to improving efficiency and reducing toxicity. In addition, stimuli-responsive nanocarriers are able to release their payload on demand at the tumor tissue site, preventing premature drug loss. This review focuses on ultrasound-triggered drug delivery by nanocarriers as a versatile, cost-efficient, non-invasive technique for improving tissue specificity and tissue penetration, and for achieving high drug concentrations at their intended site of action. It highlights aspects relevant for ultrasound-mediated drug delivery, including ultrasound parameters and resulting biological effects. Then, concepts in ultrasound-mediated drug delivery are introduced and a comprehensive overview of several types of nanoparticles used for this purpose is given. This includes an in-depth compilation of the literature on the various in vivo ultrasound-responsive drug delivery systems. Finally, toxicological and safety considerations regarding ultrasound-mediated drug delivery with nanocarriers are discussed.

scholarly journals Implantable Polymeric Drug Delivery Devices: Classification, Manufacture, Materials, and Clinical Applications

Polymers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1379 ◽  
Author(s):  
Sarah Stewart ◽  
Juan Domínguez-Robles ◽  
Ryan Donnelly ◽  
Eneko Larrañeta
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Patient Compliance ◽  
Oral Delivery ◽  
Oral Route ◽  
Clinical Applications ◽  
Drug Concentrations ◽  
Effective Delivery ◽  
Materials Used ◽  
Drug Delivery Devices

The oral route is a popular and convenient means of drug delivery. However, despite its advantages, it also has challenges. Many drugs are not suitable for oral delivery due to: first pass metabolism; less than ideal properties; and side-effects of treatment. Additionally, oral delivery relies heavily on patient compliance. Implantable drug delivery devices are an alternative system that can achieve effective delivery with lower drug concentrations, and as a result, minimise side-effects whilst increasing patient compliance. This article gives an overview of classification of these drug delivery devices; the mechanism of drug release; the materials used for manufacture; the various methods of manufacture; and examples of clinical applications of implantable drug delivery devices.

Pharmaceutical Calculations — A Basic Review

2002 ◽  
Vol 18 (5) ◽  
pp. 257-259
Author(s):  
Nicole M Russo
Keyword(s):  
Drug Delivery ◽  
Pharmaceutical Preparation ◽  
Medication Administration ◽  
Patient Specific ◽  
Specific Drug ◽  
Mathematical Concepts ◽  
Data Synthesis ◽  
Drug Concentrations ◽  
Data Source ◽  
Stock Solutions

Objective: To review mathematical topics used in pharmaceutical preparation, specifically ratios and proportions, percentage concentrations, and stock solutions. Data Source: Online pharmaceutics sources and current pharmaceutics textbooks were consulted. Data Synthesis: Ratios and proportions are basic tools for adjusting drug concentrations. Using proportions, medications can be provided in any concentration desired. By extending this technique to percentage concentrations, prescriptions can be interpreted and calculated. In the same manner, the ability to dilute stock solutions provides patient-specific drug delivery. Conclusions: The mathematical concepts of ratios and proportions, percentage concentrations, and stock dilutions are essential for correct medication administration in any setting.

Withdrawal of cefoperazone with milk after intramammary administration in dairy cows – prospective and retrospective analysis

2017 ◽  
Vol 20 (2) ◽  
pp. 261-268
Author(s):  
A. Burmańczuk ◽  
T. Grabowski ◽  
T. Błądek ◽  
C. Kowalski ◽  
P. Dębiak
Keyword(s):  
Dairy Cows ◽  
Half Life ◽  
Drug Distribution ◽  
Compartment Model ◽  
Clinical Mastitis ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Lactation Period ◽  
Milk Samples ◽  
Drug Concentrations

Abstract The aim of the study was to carry out retrospective and prospective comparative analyses of the pharmacokinetics of CEF after single intramammary (IMM) administration in cows. The prospective study (study A) was conducted on 9 dairy cows of the Polish Black-White race with clinical mastitis during the lactation period. Milk samples were collected at 2, 4, 6, 8, 10, 24, 36, 48, 72 and 84 h after single IMM administration of 250 mg of CEF to one quarter. Drug concentrations in milk samples were determined by HPLC-MS/MS technique and the results of the pharmacokinetic analysis were compared to those obtained in previous studies based on the microbiological (study B) and HPLC-UV methods (study C and D). Pharmacokinetic parameters were calculated based on adapted two-compartment model of drug distribution. One of the findings of the comparison of the analysed investigations is that the CEF kinetics determined with the microbiological method is consistent with the results obtained by the authors of this paper. Both studies yielded similar results of the key pharmacokinetic parameters related to the level of the drug distribution to tissues and elimination half-life. In the pharmacodynamic analysis, the observations in all four studies were entirely consistent and have shown lower values of T>MIC90 in healthy animals and significantly higher values in infected dairy cows. The comparison of studies A, B, C, and D revealed that the time of complete CEF wash-out of 90.90% varied and amounted to 5.7, 8.0, 2.2, and 2.2 days after administration of the drug, respectively. It was confirmed that not only the type of the analytical method but also correct sampling have a significant impact on determination of the correct value of the drug half-life after IMM administration. The comparative analysis of studies in which the milk yield was high and low allows a conclusion that this parameter in the case of CEF has no significant effect on T>MIC90.

Effect of Tumor Volume on Drug Delivery in Heterogeneous Vasculature of Human Brain Tumors

2019 ◽  
Vol 2 (2) ◽  
Author(s):  
Ajay Bhandari ◽  
Ankit Bansal ◽  
Rishav Jain ◽  
Anup Singh ◽  
Niraj Sinha
Keyword(s):  
Drug Delivery ◽  
Brain Tumors ◽  
Human Brain ◽  
Contrast Agent ◽  
Large Volume ◽  
Interstitial Fluid ◽  
Tumor Volume ◽  
Drug Distribution ◽  
Dce Mri ◽  
Concentration Of Contrast Agent

Drug distribution in tumors is strongly dependent on tumor biological properties such as tumor volume, vasculature, and porosity. An understanding of the drug distribution pattern in tumors can help in enhancing the effectiveness of anticancer treatment. A numerical model is employed to study the distribution of contrast agent in the heterogeneous vasculature of human brain tumors of different volumes. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) has been done for a number of patients with different tumor volumes. Leaky tracer kinetic model (LTKM) is employed to obtain perfusion parameters from the DCE-MRI data. These parameters are used as input in the computational fluid dynamics (CFD) model to predict interstitial fluid pressure (IFP), interstitial fluid velocity (IFV), and distribution of the contrast agent in different tumors. Numerical results demonstrate that the IFP is independent of tumor volume. On the other hand, the IFV increases as the tumor volume increases. Further, the concentration of contrast agent also increases with the tumor volume. The results obtained in this work are in line with the experimental DCE-MRI data. It is observed that large volume tumors tend to retain a higher concentration of contrast agent for a longer duration of time because of large extravasation flux and slow washout as compared to smaller tumors. These results may be qualitatively extrapolated to chemotherapeutic drug delivery, implying faster healing in large volume tumors. This study helps in understanding the effect of tumor volume on the treatment outcome for a wide range of human tumors.

scholarly journals Development of Rotational Intraperitoneal Pressurized Aerosol Chemotherapy to Enhance Drug Delivery into the Peritoneum

2021 ◽  
Author(s):  
Soo Jin Park ◽  
Eun Ji Lee ◽  
Hee Su Lee ◽  
Junsik Kim ◽  
Sunwoo Park ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Methylene Blue ◽  
Penetration Depth ◽  
Flow Rate ◽  
Tissue Concentration ◽  
Palliative Therapy ◽  
Drug Distribution ◽  
Pharmacokinetic Properties ◽  
Blue Solution ◽  
Restricted Use

Abstract Background Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been introduced as palliative therapy for treating peritoneal metastasis (PM) of solid tumors. However, restricted use in the limited countries and the uneven distribution and penetration in various regions of the peritoneal cavity ac as disadvantages of PIPAC. Thus, the KOrean Rotational Intraperitoneal pressurized Aerosol chemotherapy (KORIA) trial group developed rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) for enhancing drug delivery into the peritoneum to treat PM, and evaluated the drug distribution, tissue concentrations, penetration depth, pharmacokinetic properties, and toxicities after RIPAC with doxorubicin in pigs. Methods For delivering doxorubicin as aerosols, we used our prototype for PIPAC, which sprayed about 30-µm sized droplets through the nozzle. The mean diameter of the sprayed region was 18.5 cm, and the penetration depth ranged from 360 to 520 µm, comparable to the microinjection pump (Capnopen®; Capnomed, Villingendorf, Germany). For RIPAC, a conical pendulum motion device was added to PIPAC for rotating the nozzle. RIPAC and PIPAC were conducted using 150 ml of 1% methylene blue to evaluate drug distribution and 3.5 mg of doxorubicin in 50 ml of 0.9% NaCl to evaluate tissue concentration and penetration depth, pharmacokinetic properties, and toxicities. All agents were sprayed as aerosols via the nozzle with a velocity of 5 km/h at a flow rate of 30 ml/min under a pressure of 7 bars, and capnoperitoneum of 12 mmHg was maintained for 30 minutes. As a control, we conducted early postoperative intraperitoneal chemotherapy (EPIC) using 1% methylene blue solution with an infusion flow rate of 100 ml/min for 30 minutes and the drainage of 1 L every 10 minutes. Results RIPAC showed a wider distribution and stronger intensity than EPIC and PIPAC. Moreover, the tissue concentration and penetration depth of doxorubicin were higher in RIPAC than in PIPAC. In RIPAC, the pharmacokinetic properties reflected hemodynamic changes during capnoperitoneum, and there were no renal and hepatic toxicities related to RIPAC using doxorubicin. Conclusions RIPAC may have the potential to enhance drug delivery into the peritoneum compared to PIPAC.

scholarly journals Synovial Fluid Profile Dictates Nanopracticle Uptake into Cartilage- Implications of the Protein Corona for Novel Arthitis Treatments

2021 ◽  
Author(s):  
Ula von Mentzer ◽  
Tilia Selldén ◽  
LOISE Råberg ◽  
Gizem Erensoy ◽  
Anna-Karin Hultgård-Ekwall ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Synovial Fluid ◽  
Electrostatic Interactions ◽  
Fetal Calf Serum ◽  
Biological Fluids ◽  
Calf Serum ◽  
Protein Corona ◽  
Drug Delivery Vehicles ◽  
Drug Concentrations

<div>Intra-articular drug delivery strategies aiming to deliver drugs in diseases affected by cartilage-related issues are using electrostatic interactions to penetrate the dense cartilage matrix. This enables delivery of sufficient drug concentrations to the chondrocytes to mediate the desired therapeutic effect. As it is well known that size and charge of nanoparticles affects its interactions with the surrounding biological fluids, where proteins adsorb to the NP surface, resulting in a protein corona. There are, however, no studies investigating how the formed protein coronas affect cartilage uptake and subsequent cellular uptake, nor how they affect other cells present in the synovium of such diseases. Here, we explore the differences between the protein coronas that form when NP are incubated in synovial fluid from osteoarthritic and rheumatoid arthritis patients and compare this to results obtained using fetal calf serum (FCS), as guide for researchers working on joint drug delivery. We demonstrate that the protein corona indeed affects the uptake into cartilage, where there are major differences between the model proteins in fetal calf serum, as compared to synovial fluid from rheumatoid arthritis patients as well as osteoarthritis patients. The data suggests that when developing drug delivery vehicles for joint diseases that leverages electrostatic interactions and size, the interactions with proteins in the biological milieu is highly relevant to consider.</div>

BioMEMS Technologies for Regenerative Medicine

2008 ◽  
Vol 1139 ◽  
Author(s):  
Jeffrey T. Borenstein
Keyword(s):  
Drug Delivery ◽  
Regenerative Medicine ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Delivery Systems ◽  
Organ Shortage ◽  
Engineered Tissues ◽  
Drug Concentrations

AbstractThe emergence of BioMEMS fabrication technologies such as soft lithography, micromolding and assembly of 3D structures, and biodegradable microfluidics, are already making significant contributions to the field of regenerative medicine. Over the past decade, BioMEMS have evolved from early silicon laboratory devices to polymer-based structures and even biodegradable constructs suitable for a range of ex vivo and in vivo applications. These systems are still in the early stages of development, but the long-term potential of the technology promises to enable breakthroughs in health care challenges ranging from the systemic toxicity of drugs to the organ shortage. Ex vivo systems for organ assist applications are emerging for the liver, kidney and lung, and the precision and scalability of BioMEMS fabrication techniques offer the promise of dramatic improvements in device performance and patient outcomes.Ultimately, the greatest benefit from BioMEMS technologies will be realized in applications for implantable devices and systems. Principal advantages include the extreme levels of achievable miniaturization, integration of multiple functions such as delivery, sensing and closed loop control, and the ability of precision microscale and nanoscale features to reproduce the cellular microenvironment to sustain long-term functionality of engineered tissues. Drug delivery systems based on BioMEMS technologies are enabling local, programmable control over drug concentrations and pharmacokinetics for a broad spectrum of conditions and target organs. BioMEMS fabrication methods are also being applied to the development of engineered tissues for applications such as wound healing, microvascular networks and bioartificial organs. Here we review recent progress in BioMEMS-based drug delivery systems, engineered tissue constructs and organ assist devices for a range of ex vivo and in vivo applications in regenerative medicine.

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