Ultrasound -Triggered Drug Delivery with Contrast Imaging: Effect of Microencapsulation Method

1998 ◽  
Vol 550 ◽  
Author(s):  
M.A. Wheatley ◽  
D. El-Sherif ◽  
R. Basude ◽  
R. Shimp ◽  
P. Narayan

AbstractA method for preparation of hollow, biodegradable polymeric microcapsules for use as contrast agents is described, and strategies for their use in concomitant imaging and drug delivery are outlined. Compared with X-ray or magnetic resonance imaging, diagnostic ultrasound is a safe, relatively inexpensive imaging technique, which allows the physician to view real-time images. Contrast agents are being developed which will greatly enhance the contrast of the received image, when injected into the patients blood stream. We have developed hollow polymeric CA based upon the ability to microencapsulate a solid core of ammonium carbonate which is then removed by decomposition and freeze-drying. The polymer poly D,L(lactide-co-glycolide) (PLGA) was chosen for it's FDA approval, and because it has the most rapid in vivo degradation of the α-hydroxy acid series. Spray dried and solvent extraction samples were used to test the concept of concomitant drug delivery and imaging. The method of fabrication had an important effect on the drug loading by adsorption, and on the amount of drug that was released when the capsules were insonated with ultrasound in the medical imaging range. Both were greater for spray dried samples. Both frequency and pressure of insonation also influenced release. The most dramatic increase in release was after 5 minutes for the 10 Mhz low (1.25 MPa) pressure insonation, which showed 316% greater release than control, a total of 1.89 mg.

2010 ◽  
Vol 1257 ◽  
Author(s):  
Andrea Fornara ◽  
Alberto Recalenda ◽  
Jian Qin ◽  
Abhilash Sugunan ◽  
Fei Ye ◽  
...  

AbstractNanoparticles consisting of different biocompatible materials are attracting a lot of interest in the biomedical area as useful tools for drug delivery, photo-therapy and contrast enhancement agents in MRI, fluorescence and confocal microscopy. This work mainly focuses on the synthesis of polymeric/inorganic multifunctional nanoparticles (PIMN) based on biocompatible di-block copolymer poly(L,L-lactide-co-ethylene glycol) (PLLA-PEG) via an emulsion-evaporation method. Besides containing a hydrophobic drug (Indomethacin), these polymeric nanoparticles incorporate different visualization agents such as superparamagnetic iron oxide nanoparticles (SPION) and fluorescent Quantum Dots (QDs) that are used as contrast agents for Magnetic Resonance Imaging (MRI) and fluorescence microscopy together. Gold Nanorods are also incorporated in such nanostructures to allow simultaneous visualization and photodynamic therapy. MRI studies are performed with different loading of SPION into PIMN, showing an enhancement in T2 contrast superior to commercial contrast agents. Core-shell QDs absorption and emission spectra are recorded before and after their loading into PIMN. With these polymeric/inorganic multifunctional nanoparticles, both MRI visualization and confocal fluorescence microscopy studies can be performed. Gold nanorods are also synthesized and incorporated into PIMN without changing their longitudinal absorption peak usable for lased excitation and phototherapy. In-vitro cytotoxicity studies have also been performed to confirm the low cytotoxicity of PIMN for further in-vivo studies.


2021 ◽  
Vol 16 (7) ◽  
pp. 1029-1036
Author(s):  
Hongzhu Wang ◽  
Mengxun Chen ◽  
Liping Song ◽  
Youju Huang

A key challenge for nanoparticles-based drug delivery system is to achieve manageable drug release in tumour cell. In this study, a versatile system combining photothermal therapy and controllable drug release for tumour cells using temperature-sensitive block copolymer coupled Au NRs@SiO2 is reported. While the Au NRs serve as hyperthermal agent and the mesoporous silica was used to improve the drug loading and decrease biotoxicity. The block copolymer acted as “gatekeeper” to regulate the release of model drug (Doxorubicin hydrochloride, DOX). Through in vivo and in vitro experiments, we achieved the truly controllable drug release and photothermal therapy with the collaborative effect of the three constituents of the nanocomposites. The reported nanocomposites pave the way to high-performance controllable drug release and photothermal therapy system.


Nanoscale ◽  
2019 ◽  
Vol 11 (43) ◽  
pp. 20956-20967 ◽  
Author(s):  
Qiaojuan Jia ◽  
Zhenzhen Li ◽  
Chuanpan Guo ◽  
Xiaoyu Huang ◽  
Yingpan Song ◽  
...  

A biocompatible γ-CD-MOF based DDS with high drug loading and full drug release was prepared and effective tumor growth inhibition was achieved in vivo.


Author(s):  
Upasana Yadav ◽  
Angshuman Ray Chowdhuri ◽  
Sumanta Kumar Sahu ◽  
Nuzhat Husain ◽  
Qamar Rehman

  Objective: In this study, we have made an attempt to the developed formulation of nanoparticles (NPs) of telmisartan (TLM) incorporated in carboxymethyl chitosan (CMCS) for the better drug delivery and enhanced bioavailability.Materials and Methods: The NPs size and morphology were investigated by high-resolution transmission electron microscopy and field emission scanning electron microscopy, respectively. The crystal structures and surface functional groups were analyzed using X-ray diffraction pattern, and Fourier transform infrared spectroscopy, respectively.Results: To increase the solubility of TLM by targeted delivery of the drug through polymeric NPs is an alternative efficient, option for increasing the solubility. TLM nanosuspension powders were successfully formulated for dissolution and bioavailability enhancement of the drug. We focused on evaluating the influence of particle size and crystalline state on the in vitro and in vivo performance of TLM.Conclusion: In summary, we have developed a new approach toward the delivery of poorly water-soluble drug TLM by CMCS NPs. The particles having a good drug loading content and drug encapsulation efficiency. The cytotoxicity of the synthesized NPs is also very less.


2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Fransisca Leonard ◽  
Katherine Margulis ◽  
Xuewu Liu ◽  
Srimeenakshi Srinivasan ◽  
Shlomo Magdassi ◽  
...  

AbstractEnsuring drug loading efficiency and consistency is one of the most critical stages in engineering drug delivery vectors based on porous materials. Here we propose a technique to significantly enhance the effciency of loading by employing simple and widely available methods: applying low pressure with and without centrifugation. Our results point toward the advantages of the proposed method over the passive loading, especially when the difference between the dimensions of loaded materials and the pore diameter is small, an increase of up to 20-fold can be observed. The technique described in this study can be used for efficient and reproducible loading of porous materials with therapeutic molecules, nanoparticles and contrast imaging agents for biomedical applications.


2005 ◽  
Vol 04 (05n06) ◽  
pp. 855-861 ◽  
Author(s):  
MARTIN GARNETT

The use of nanosized materials changes the way in which drugs are handled by the body and offers opportunities to improve drug delivery. The physiological mechanisms controlling the distribution of nanosized materials (enhanced permeability and retention effect, cellular uptake pathways and opsonisation/elimination of nanoparticles) are described. Two different nanosized drug delivery systems are considered; drug delivery and DNA delivery. The deficiencies of currently available biodegradable polymers for preparation of drug containing nanoparticles are mainly the amount of drug that can be incorporated and the rapid rate of drug release. The development of new biodegradable polymers which can interact with the drug and so significantly increase drug loading and decrease the rate of drug release are outlined. DNA delivery necessitates overcoming a variety of biological barriers. We are developing polyelectrolyte complexes of DNA with cationic polyamidoamines (PAA) as a delivery system. Complexing PAA with DNA results in good transfection of cells in vitro. However, in vivo, a more complex arrangement of PAA, Polyethylene glycol-PAA copolymers, DNA and the use of ligands will be required. Despite these efforts, further developments will be needed in nanotechnology for both drug and DNA nanoparticle delivery systems to achieve our clinical objectives.


2021 ◽  
Author(s):  
Boxun Liu ◽  
Zhizhong Jin ◽  
Haiyan Chen ◽  
Lun Liang ◽  
Yao Li ◽  
...  

Abstract Electrospun membranes are attracting interest as a drug delivery system because of their material composition flexibility and versatile drug loading. In this study, the electrospun membrane was loaded with doxorubicin (DOX) via electrostatic adsorption for long-term drug delivery. DOX loading process was optimized by varying temperature, time, drug concentration, pH, and ionic strength of solutions. The loading process did not impair the structural properties of the membrane. Next, we investigated the drug release kinetics using spectroscopic techniques. The composite membranes released 22% of the adsorbed DOX over the first 48 h, followed by a slower and sustained release over 4 weeks. The DOX release was sensitive to acidic solutions that the release rate at pH 6.0 was 1.27 times as that at pH 7.4. The DOX-loaded membranes were found to be cytotoxic to U-87 MG cells in vitro that decreased the cell viability from 82.92% to 25.49% from 24 h to 72 h of co-incubation. These membranes showed strong efficacy in suppressing tumour growth in vivo in glioblastoma-bearing mice that decreased the tumour volume by 77.33% compared to blank membrane-treated group on Day 20. In conclusion, we have developed an effective approach to load DOX within a clinically-approved poly (L-lactic acid)/gelatin membrane for local and long-term delivery of DOX for the treatment of glioblastoma.


2021 ◽  
Vol 14 (4) ◽  
pp. 1538-1543
Author(s):  
Raghav Mishra

Due to the complexity of gastric emptying, as well as its considerable variability, the in vivo efficacy of drug delivery devices cannot be predicted. When it pertains to drugs with an absorption window in the upper small intestine, a controlled drug delivery system with a longer residence period in the stomach may be of considerable practical significance. Recent developments have shown that floating microspheres are particularly well suited for mixing sustained and delayed releases to achieve a variety of release models with a minimal risk of dumping. The aim of present investigation is to develop and analyze the floating microspheres of amethopterin, which after oral administration could increase the gastric residence time and enhance the bioavailability of the drug by sustained release and minimize the dose dependent side effects as well as improves patient compliance. Floating microspheres of ethyl cellulose, Polyvinyl alcohol and polyvinyl pyrrolidone-K90 were formulated by emulsification solvent evaporation technique. The various parameters of prepared microspheres were studied for SEM, flow properties, buoyancy, yield, percent drug loading, in vitro dissolution studies, stability in different pH and FTIR studies. Microspheres prepared with different concentrations of polymers were spherical in shape with smooth surface. The size of microspheres was in range of 256.02 µm and 362.84 µm. Good drug entrapment and buoyancy were observed for formulation F2. The in vitro drug release after 6h was found to be in range from 58.15% to 96.28%. It was established that the newly created floating microspheres of Amethopterin provide an appropriate and practical solution for the sustained release of medication over a longer period of time, resulting in increased oral bioavailability, effectiveness, as well as better patient compliance.


Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 210 ◽  
Author(s):  
Jeand Baloch ◽  
Muhammad Farhan Sohail ◽  
Hafiz Shaib Sarwar ◽  
Maria Hassan Kiani ◽  
Gul Majid Khan ◽  
...  

Background and Objectives: Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer many valuable opportunities in drug delivery. Chlorpromazine, an antipsychotic agent with poor aqueous solubility—with extensive first-pass metabolism—can be a suitable candidate for the development of SNEDDS. The current study was designed to develop triglyceride-based SNEDDS of chlorpromazine to achieve improved solubility, stability, and oral bioavailability. Materials and Methods: Fifteen SNEDDS formulations of each short, medium, and long chain, triglycerides were synthesized and characterized to achieve optimized formulation. The optimized formulation was characterized for several in vitro and in vivo parameters. Results: Particle size, zeta potential, and drug loading of the optimized SNEDDS (LCT14) were found to be 178 ± 16, −21.4, and 85.5%, respectively. Long chain triglyceride (LCT14) showed a 1.5-fold increased elimination half-life (p < 0.01), up to 6-fold increased oral bioavailability, and 1.7-fold decreased plasma clearance rate (p < 0.01) compared to a drug suspension. Conclusion: The findings suggest that SNEDDS based on long-chain triglycerides (LCT14) formulations seem to be a promising alternative for improving the oral bioavailability of chlorpromazine.


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