Synthesis, In Vitro and In Vivo Release Kinetics, and Anti-HIV Activity of A Sustained-Release Prodrug (mPEG-AZT) of 3′-Azido-3′-deoxythymidine (AZT, Zidovudine)

ChemMedChem ◽  
2010 ◽  
Vol 5 (11) ◽  
pp. 1893-1898 ◽  
Author(s):  
Wenjun Li ◽  
Yu Chang ◽  
Peng Zhan ◽  
Na Zhang ◽  
Xinyong Liu ◽  
...  
Keyword(s):  
Sustained Release ◽  
Release Kinetics ◽  
In Vivo Release ◽  
Anti Hiv

Understanding the burst release phenomenon: toward designing effective nanoparticulate drug-delivery systems

2020 ◽  
pp. 00-00
Author(s):  
Sourav Bhattacharjee
Keyword(s):  
Drug Delivery ◽  
Sustained Release ◽  
Mathematical Models ◽  
Drug Delivery Systems ◽  
Release Kinetics ◽  
Burst Release ◽  
Future Directions ◽  
Short Period

Burst release of encapsulated drug with release of a significant fraction of payload into release medium within a short period, both in vitro and in vivo, remains a challenge for translation. Such unpredictable and uncontrolled release is often undesirable, especially from the perspective of developing sustained-release formulations. Moreover, a brisk release of the payload upsets optimal release kinetics. This account strives toward understanding burst release noticed in nanocarriers and investigates its causes. Various mathematical models to explain such untimely release were also examined, including their strengths and weaknesses. Finally, the account revisits current techniques of limiting burst release from nanocarriers and prioritizes future directions that harbor potential of fruitful translation by reducing such occurrences.

scholarly journals Biocompatible PLGA-Mesoporous Silicon Microspheres for the Controlled Release of BMP-2 for Bone Augmentation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 118 ◽  
Author(s):  
Silvia Minardi ◽  
Joseph S. Fernandez-Moure ◽  
Dongmei Fan ◽  
Matthew B. Murphy ◽  
Iman K. Yazdi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sustained Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Bone Morphogenetic Protein 2 ◽  
Osteogenic Potential ◽  
Bone Augmentation

Bone morphogenetic protein-2 (BMP-2) has been demonstrated to be one of the most vital osteogenic factors for bone augmentation. However, its uncontrolled administration has been associated with catastrophic side effects, which compromised its clinical use. To overcome these limitations, we aimed at developing a safer controlled and sustained release of BMP-2, utilizing poly(lactic-co-glycolic acid)-multistage vector composite microspheres (PLGA-MSV). The loading and release of BMP-2 from PLGA-MSV and its osteogenic potential in vitro and in vivo was evaluated. BMP-2 in vitro release kinetics was assessed by ELISA assay. It was found that PLGA-MSV achieved a longer and sustained release of BMP-2. Cell cytotoxicity and differentiation were evaluated in vitro by MTT and alkaline phosphatase (ALP) activity assays, respectively, with rat mesenchymal stem cells. The MTT results confirmed that PLGA-MSVs were not toxic to cells. ALP test demonstrated that the bioactivity of BMP-2 released from the PLGA-MSV was preserved, as it allowed for the osteogenic differentiation of rat mesenchymal stem cells, in vitro. The biocompatible, biodegradable, and osteogenic PLGA-MSVs system could be an ideal candidate for the safe use of BMP-2 in orthopedic tissue engineering applications.

scholarly journals Local Myotoxicity from Sustained Release of Bupivacaine from Microparticles

2008 ◽  
Vol 108 (5) ◽  
pp. 921-928 ◽  
Author(s):  
Robert Padera ◽  
Evangelia Bellas ◽  
Julie Y. Tse ◽  
Daphne Hao ◽  
Daniel S. Kohane
Keyword(s):  
Sustained Release ◽  
Local Anesthetics ◽  
Release Kinetics ◽  
C2c12 Myotubes ◽  
Nerve Blocks ◽  
Carrier Fluid ◽  
Local Toxicity ◽  
Particulate Delivery

Background Sustained release of local anesthetics is frequently associated with myotoxicity. The authors investigated the role of particulate delivery systems and of the pattern of drug release in causing myotoxicity. Methods Rats were given sciatic nerve blocks with bupivacaine solutions, two types of bupivacaine-containing microparticles (polymeric microspheres and lipid-protein-sugar particles), or blank particles with or without bupivacaine in the carrier fluid. Myotoxicity was scored in histologic sections of the injection sites. Bupivacaine release kinetics from the particles were measured. Myotoxicity of a range of bupivacaine concentrations from exposures up to 3 weeks was assessed in C2C12 myotubes, with or without microparticles. Results Both types of bupivacaine-loaded microparticles, but not blank particles, were associated with myotoxicity. Whereas 0.5% bupivacaine solution caused little myotoxicity, a concentration of bupivacaine that mimicked the amount of bupivacaine released initially from particles caused myotoxicity. Local anesthetics showed both concentration and time-dependent myotoxicity in C2C12s. Importantly, even very low concentrations that were nontoxic over brief exposures became highly toxic after days or weeks of exposure. The presence of particles did not increase bupivacaine myotoxicity in vitro but did in vivo. Findings applied to both particle types. Conclusions Whereas the release vehicles themselves were not myotoxic, both burst and extended release of bupivacaine were. A possible implication of the latter finding is that myotoxicity is an inevitable concomitant of sustained release of local anesthetics. Particles, and perhaps other vehicles, may enhance local toxicity through indirect mechanisms.

Formulation and Evaluation of Itopride Hydrochloride Floating Beads for Gastroretentive Delivery

2013 ◽  
Vol 6 (4) ◽  
pp. 2269-2280
Author(s):  
Nagratna Dhople ◽  
P N Dandag ◽  
A P Gadad ◽  
C K Pandey ◽  
Masthiholimath V S
Keyword(s):  
Sustained Release ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Sustained Release Formulation ◽  
Prokinetic Drug ◽  
Drug Entrapment Efficiency ◽  
Itopride Hydrochloride ◽  
Vitro Release

A gastroretentive sustained release system of itopride hydrochloride was formulated to increase the gastric residence time and modulate its release behavior. Itopride hydrochloride is a prokinetic drug used in the treatment of gastroeosophageal reflux disease, Non-ulcer dyspepsia and as an antiemetic. Hence, itopride hydrochloride beads were prepared by emulsion gelation method by employing low methoxy pectin and sodium alginate as sustained release polymers in three different ratios alone and in combination and sunflower oil was used to enable floating property to the beads. The effect of variation in polymer and their concentration was investigated. The beads were evaluated for production yield, particle size, swelling index, density measurement, buoyancy, drug content, drug entrapment efficiency, in vitro release characteristics and release kinetic study. Based on drug entrapment efficiency, buoyancy, swelling and in vitro release, F9 was selected as the optimized formulation. F9 was further subjected to surface morphology by SEM, in vitro release comparison with marketed formulation, in vivo floating study in rabbits and stability study for 90 days. In vitro release follows zero order and fitted in Korsmeyer peppas model (Non-Fickian release). Therefore, the rate of drug release is due to the combined effect of drug diffusion and polymer swelling. The in vivo X-ray studies revealed that the beads were floating in the rabbit stomach up to 10 hours. Thus, it was concluded that the sustained release formulation containing itopride hydrochloride was found to improve patient compliance, minimize the side effects and decrease the frequency of administration.

Utilizing ICG Spectroscopical Properties for Real-Time Nanoparticle Release Quantification In vitro and In vivo in Imaging Setups

2020 ◽  
Vol 26 (31) ◽  
pp. 3828-3833 ◽  
Author(s):  
Tuula Peñate-Medina ◽  
Eike Kraas ◽  
Kunliang Luo ◽  
Jana Humbert ◽  
Hanwen Zhu ◽  
...  
Keyword(s):  
Release Kinetics ◽  
Pure Water ◽  
Squamous Carcinoma ◽  
Peak Shift ◽  
Intensity Increase ◽  
Nude Mouse Model ◽  
Absorption And Emission ◽  
Squamous Carcinoma Cells

Background: Nanoparticle imaging and tracking the release of the loaded material from the nanoparticle system have attracted significant attention in recent years. If the release of the loaded molecules could be monitored reliably in vivo, it would speed up the development of drug delivery systems remarkably. Methods: Here, we test a system that uses indocyanine green (ICG) as a fluorescent agent for studying release kinetics in vitro and in vivo from the lipid iron nanoparticle delivery system. The ICG spectral properties like its concentration dependence, sensitivity and the fluctuation of the absorption and emission wavelengths can be utilized for gathering information about the change of the ICG surrounding. Results: We have found that the absorption, fluorescence, and photoacoustic spectra of ICG in lipid iron nanoparticles differ from the spectra of ICG in pure water and plasma. We followed the ICG containing liposomal nanoparticle uptake into squamous carcinoma cells (SCC) by fluorescence microscopy and the in vivo uptake into SCC tumors in an orthotopic xenograft nude mouse model under a surgical microscope. Conclusion: Absorption and emission properties of ICG in the different solvent environment, like in plasma and human serum albumin, differ from those in aqueous solution. Photoacoustic spectral imaging confirmed a peak shift towards longer wavelengths and an intensity increase of ICG when bound to the lipids. The SCC cells showed that the ICG containing liposomes bind to the cell surface but are not internalized in the SCC-9 cells after 60 minutes of incubation. We also showed here that ICG containing liposomal nanoparticles can be traced under a surgical camera in vivo in orthotopic SCC xenografts in mice.

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