drug dispersion
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2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Omar Y. Mady ◽  
Adam A. Al-Shoubki ◽  
Ahmed A. Donia ◽  
Waseem Qasim

AbstractPenetration enhancement of metformin hydrochloride via its molecular dispersion in sorbitan monostearate microparticles is reported. This represents basic philosophy to maximize its entrapment for maximum penetration effect. Drug dispersion in sorbitan monostearate with different theoretical drug contents (TDC) were prepared. Products showed excellent micromeritics and actual drug content (ADC) increased by increasing TDC. The partition coefficient of the drug products showed huge improvement. This indicates the drug entrapped in the polar part of sorbitan monostearate as a special image which effects on the drug release. The drug permeation profiles from the different products are overlapped with nearly equal permeation parameters. The permeation results suggested the main driving force for improving the drug paracellular pathway is its dispersion in sorbitan monostearate and is independent of ADC. Pharmacodynamic of the products showed a significant improvement than the drug alone at p ˂ 0.05. ANOVA test indicated the insignificant pharmacodynamic difference between the low, middle, and high ADC of the products. An excellent correlation founded between the drug permeation and pharmacodynamic precents. Drug permeation driving force via the paracellular pathway is its entrapment in sorbitan monostearate and independent on ADC. The technique is simple and the products had excellent micromeritics.



2020 ◽  
Vol 248 ◽  
pp. 116724
Author(s):  
Ednaldo Gomes do Nascimento ◽  
Eduardo Pereira de Azevedo ◽  
Mariana Farias Alves-Silva ◽  
Cícero Flávio S. Aragão ◽  
Matheus F. Fernandes-Pedrosa ◽  
...  


2020 ◽  
Vol 106 ◽  
pp. 106936
Author(s):  
Robert J. Connor ◽  
Darin M. Taverna ◽  
Karla Thrall ◽  
Michael J. LaBarre ◽  
David W. Kang


2020 ◽  
Author(s):  
Jia-Pu Liang ◽  
Robert P. Accolla ◽  
Kaiyuan Jiang ◽  
Ying Li ◽  
Cherie L. Stabler

AbstractThe simultaneous local delivery of anti-inflammatory and pro-angiogenic agents via biomaterial scaffolds presents a promising method for improving the engraftment of tissue-engineered implants while avoiding potentially detrimental systemic delivery. In this study, PDMS microbeads were loaded with either anti-inflammatory dexamethasone (Dex) or pro-angiogenic 17β-estradiol (E2) and subsequently integrated into a single macroporous scaffold to create a controlled, dual drug-delivery platform. Compared to a standard monolithic drug dispersion scaffold, macroporous scaffolds containing drug-loaded microbeads exhibited reduced initial burst release and increased the durability of drug release for both agents. Incubation of scaffolds with LPS-stimulated M1 macrophages found that Dex suppressed the production of pro-inflammatory and pro-angiogenic factors, when compared to drug-free control scaffolds; however, the co-incubation of macrophages with Dex and E2 scaffolds restored their pro-angiogenic features. Following implantation, Dex-loaded microbead scaffolds (Dex-µBS) suppressed host cell infiltration and integration, when compared to controls. In contrast, the co-delivery of dexamethasone with estrogen from the microbead scaffold (Dex/E2-µBS) dampened overall host cell infiltration but restored graft vascularization. These results demonstrate the utility of a microbead scaffold approach for the controlled, tailored, and local release of multiple drugs from an open framework implant. It further highlights the complementary impacts of local Dex and E2 delivery to direct the healthy integration of implants, which has broad applications to the field of tissue engineering and regenerative medicine.



Author(s):  
Jung Tae Kim ◽  
Jeong Yun Park ◽  
Hyun Jung Lee ◽  
Young Ju Cheon

The purpose of these practice guidelines is to offer and share strategies for preventing extravasation and measures for handling drugs known to cause tissue necrosis, which may occur even with the most skilled experts at intravenous (IV) injection. Herein, general knowledge about extravasation is first described, including its definition, incidence, risk factors, diagnosis, differential diagnosis, and extravasation injuries. Management of extravasation includes nursing intervention and thermal application. At the first sign of extravasation, nursing intervention with following steps is recommended: stop administration of IV fluids immediately, disconnect the IV tube from the cannula, aspirate any remaining drug from the cannula, administer drug-specific antidote, and notify the physician. Local thermal treatments are used to decrease the site reaction and absorption of the infiltrate. Local cooling (ice packs) aids in vasoconstriction, theoretically limiting the drug dispersion. Although clear benefit has not been demonstrated with thermal applications, it remains a standard supportive care. The recommended application schedule for both warm and cold applications is 15 to 20 minutes, every 4 hours, for 24 to 48 hours. For prevention of extravasation, health professionals should be familiar with the extravasation management standard guidelines. They should regularly check the extravasation kit, assess patients’ sensory changes, tingling or burning, and always pay attention to patients’ words. The medical team’s continuous education on extravasation is essential. With the practical use of these guidelines, it is expected to reduce the occurrence rate of extravasation and contribute to patient care improvement.



2020 ◽  
Vol 21 (12) ◽  
pp. 4493
Author(s):  
Lewis H. Bender ◽  
Franco Abbate ◽  
Ian B. Walters

The recent development of immune-based therapies has improved the outcome for cancer patients; however, adjuvant therapies remain an important line of treatment for several cancer types. To maximize efficacy, checkpoint inhibitors are often combined with cytotoxic agents. While this approach often leads to increased tumor regression, higher off target toxicity often results in certain patients. This report describes a novel formulation comprising a unique amphiphilic molecule, 8-((2-hydroxybenzoyl)amino)octanoate (SHAO), that non-covalently interacts with payloads to increase drug dispersion and diffusion when dosed intratumorally (IT) into solid tumors. SHAO is co-formulated with cisplatin and vinblastine (referred to as INT230-6). IT dosing of the novel formulation achieved greater tumor growth inhibition and improved survival in in vivo tumor models compared to the same drugs without enhancer given intravenously or IT. INT230-6 treatment increased immune infiltrating cells in injected tumors with 10% to 20% of the animals having complete responses and developing systemic immunity to the cancer. INT230-6 was also shown to be synergistic with programmed cell death protein 1 (PD-1) antibodies at improving survival and increasing complete responses. INT230-6 induced significant tumor necrosis potentially releasing antigens to induce the systemic immune-based anti-cancer attack. This research demonstrates a novel, local treatment approach for cancer that minimizes systemic toxicity while stimulating adaptive immunity.



Author(s):  
MANISH YADAV

Objective: The purpose of this investigation was to design and develop controlled release floating beads of Ketoprofenand Pantoprazole sodium. To determine the interaction between excipients used and to find out the nature of drug in the formulation, X-ray diffraction (XRD) and Differential Scanning Colorimetry (DSC) studies were performed. Methods: The beads were prepared by ionotropic gelation technique. Sodium alginate and HPMC E5LV was dissolved in deionized water (9:1 sodium alginate: HPMC E5LV) at a concentration of 1-3 % w/v using gentle heat on the water bath. After getting a clear solution, an accurately weighed quantity of Pantoprazole sodium was added and dispersed uniformly into the solution. In a separate beaker, Ketoprofen and calcium carbonate (1:1, Sodium alginate: CaCl2) was dispersed in water and mixed with sodium alginate solution containing Pantoprazole sodium. The bubble-free sodium alginate-drug dispersion (20 ml) was added dropwise via a 22-guage hypodermic needle fitted with a 10 ml syringe into 100 ml of calcium chloride solution (1-2 % w/v) containing 10 % glacial acetic acid and stirred at 400 rpm for 15 min. Results: From the experimental study, it was concluded that optimized batch F9 showed good micromeritic properties, entrapment efficiency and releases the drug slowly and completely for 12 h as beads remain in floating condition throughout dissolution study that assures prepared formulation remain floated in the stomach without its early passing to lower Gastro-Intestinal Tract(GIT) side. The percentage of drugs release of Ketoprofen and Pantoprazole Sodium was 96.56% and 97.74%, respectively at 12 h. Conclusion: Combination of different polymer provide sustained release pattern in different concentration. Formulation F9 gives good floating behavior using sodium alginate and HPMC hydroxypropyl methylcellulose in different ratios. In the present study, a satisfactory attempt has been made to formulate gastro retentive floating beads of Ketoprofen and Pantoprazole sodium.



2019 ◽  
Vol 303 ◽  
pp. 12-23 ◽  
Author(s):  
Rayane S.C.M.Q. Antonino ◽  
Thais L. Nascimento ◽  
Edilson R. de Oliveira Junior ◽  
Leonardo G. Souza ◽  
Aline C. Batista ◽  
...  


2019 ◽  
Vol 89 (12) ◽  
pp. 1823
Author(s):  
Т.Е. Суханова ◽  
М.Э. Вылегжанина ◽  
А.Я. Волков ◽  
E.Р. Гасилова ◽  
А.А. Кутин ◽  
...  

Using the methods of atomic force microscopy, optical microscopy, X-ray diffraction analysis, dynamic and static light scattering, we studied the morphology, structure, and optical properties of compositions based on biodegradable polymer nanoparticles prepared from mixtures of polycaprolactone and a stabilizer - polyvinyl alcohol containing the antitumor preparation 5-fluorouracil. Studies have shown significant changes in the morphology of the resulting compositions depending on the stabilizer content. No crystalline reflections corresponding to 5-fluorouracil were found, which indicates a high degree of the drug dispersion in the polycaprolactone polymer matrix. Correlations between structural and morphological parameters, composition, stabilizer concentration and encapsulation efficiency of the 5-fluorouracil drug in the compositions have been established.



2018 ◽  
Vol 861 ◽  
pp. 679-720 ◽  
Author(s):  
J. J. Lawrence ◽  
W. Coenen ◽  
A. L. Sánchez ◽  
G. Pawlak ◽  
C. Martínez-Bazán ◽  
...  

This paper investigates the transport of a solute carried by the cerebrospinal fluid (CSF) in the spinal canal. The analysis is motivated by the need for a better understanding of drug dispersion in connection with intrathecal drug delivery (ITDD), a medical procedure used for treatment of some cancers, infections and pain, involving the delivery of the drug to the central nervous system by direct injection into the CSF via the lumbar route. The description accounts for the CSF motion in the spinal canal, described in our recent publication (Sánchez et al., J. Fluid Mech., vol. 841, 2018, pp. 203–227). The Eulerian velocity field includes an oscillatory component with angular frequency $\unicode[STIX]{x1D714}$, equal to that of the cardiac cycle, and associated tidal volumes that are a factor $\unicode[STIX]{x1D700}\ll 1$ smaller than the total CSF volume in the spinal canal, with the small velocity corrections resulting from convective acceleration providing a steady-streaming component with characteristic residence times of order $\unicode[STIX]{x1D700}^{-2}\unicode[STIX]{x1D714}^{-1}\gg \unicode[STIX]{x1D714}^{-1}$. An asymptotic analysis for $\unicode[STIX]{x1D700}\ll 1$ accounting for the two time scales $\unicode[STIX]{x1D714}^{-1}$ and $\unicode[STIX]{x1D700}^{-2}\unicode[STIX]{x1D714}^{-1}$ is used to investigate the prevailing drug-dispersion mechanisms and their dependence on the solute diffusivity, measured by the Schmidt number $S$. Convective transport driven by the time-averaged Lagrangian velocity, obtained as the sum of the Eulerian steady-streaming velocity and the Stokes-drift velocity associated with the non-uniform pulsating flow, is found to be important for all values of $S$. By way of contrast, shear-enhanced Taylor dispersion, which is important for values of $S$ of order unity, is shown to be negligibly small for the large values $S\sim \unicode[STIX]{x1D700}^{-2}\gg 1$ corresponding to the molecular diffusivities of all ITDD drugs. Results for a model geometry indicate that a simplified equation derived in the intermediate limit $1\ll S\ll \unicode[STIX]{x1D700}^{-2}$ provides sufficient accuracy under most conditions, and therefore could constitute an attractive reduced model for future quantitative analyses of drug dispersion in the spinal canal. The results can be used to quantify dependences of the drug-dispersion rate on the frequency and amplitude of the pulsation of the intracranial pressure, the compliance and specific geometry of the spinal canal and the molecular diffusivity of the drug.



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