Effect of mean diameter and polydispersity of PLG microspheres on drug release: Experiment and theory

Berchane, Nader; Carson, Kenneth; Rice‐Ficht, Allison C.; Andrews, Malcolm J.

doi:10.1016/j.ijpharm.2006.12.037

Cited by 92 publications

(60 citation statements)

References 23 publications

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“…Other batches of microspheres had sizes that were not significantly different from the size of gelatin microspheres, except those prepared with 5.0% (m/V) mucuna gum with 3 h crosslinking and 10.0% (m/V) mucuna gum with 1 h crosslinking. Particle size of microparticles/microspheres is a very important parameter, since it affects drug release and pharmacokinetics (20). For microspheres engineered for parenteral administration, large particles will find it difficult to pass through the syringe.…”

Section: Resultsmentioning

confidence: 99%

Mucuna gum microspheres for oral delivery of glibenclamide: In vitro evaluation

Attama

Nwabunze²

2007

Acta Pharmaceutica

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Microspheres refer to the micro-particulate polymer based drug delivery system with an average particle size larger than 1 µm. Microsphere carrier systems made from naturally occurring biodegradable polymers have attracted considerable attention for several 161 Acta Pharm. 57 (2007) An investigation into the suitability of mucuna gum microspheres for oral delivery of glibenclamide is presented. Mucuna gum microspheres were formulated under different conditions of polymer concentration and crosslinking time at constant speed. The formulated microspheres were thereafter loaded with glibenclamide by the remote loading process. The microspheres were evaluated according to particle size, yield, loading efficiency and swelling.In vitro release of glibenclamide from the microspheres was studied in simulated intestinal fluid (SIF, pH 7.4). The release data was fitted into two release models to investigate the mechanism of glibenclamide release from the microspheres. All the microspheres showed good swelling characteristics in distilled water. The investigation revealed that the microspheres produced with 5% (m/V) mucuna gum with a crosslinking time of 5 h had the optimum prolonged release pattern. The microspheres produced using 10% (m/V) mucuna gum with a crosslinking time of 1 h had the highest delayed release of the incorporated drug, whereas those without crosslinking had the fastest release. The Ritger-Peppas case I transport model appeared to have adequately described the release process as about 54% of the batches of microspheres conformed to this model. This implies that a formulation of glibenclamide-loaded mucuna gum microspheres is likely to offer a reliable means of delivering glibenclamide by the oral route.

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Section: Resultsmentioning

confidence: 99%

Mucuna gum microspheres for oral delivery of glibenclamide: In vitro evaluation

Attama

Nwabunze²

2007

Acta Pharmaceutica

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“…These include changing the polymer lactide/glycolide ratio 45 or molecular weight, 46 introducing copolymers such as polycaprolactone 47 or additives such as poly(ethylene glycol), 33 or by simply altering microsphere size. 48 PLGA microsphere systems have been shown to be capable of degradation over timescales of a few weeks 46,49 to several months. 50,51 Protein stability is always one of the biggest concerns in drug delivery systems.…”

Section: Resultsmentioning

confidence: 99%

Design of Protein‐Releasing Chitosan Channels

Kim¹,

Tator²,

Shoichet³

2008

Biotechnology Progress

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After traumatic injury to the spinal cord, the neural tissue degenerates, resulting in lost function below the site of injury. Promoting axonal regeneration after injury remains a challenge; however, guidance channels have demonstrated some success when combined with cellular and protein therapies. One of the limitations of current guidance channels is the inability to deliver therapeutically relevant molecules in situ, within the guidance channel, to enhance regeneration. In an effort to provide a system for local and sustained drug release, poly(lactide-co-glycolide) (PLGA) microspheres were embedded into chitosan guidance channels by a novel spin-coating technique. The method was designed to create guidance channels with the appropriate dimensions for implantation into the spinal cord, with special attention paid to the wall thickness. The release and bioactivity of a model protein, alkaline phosphatase, was followed from the channels and compared to those from free-floating microspheres over a 90-day period. Since chitosan formulations often require the use of acidic solutions, careful attention was paid to redesign the process to minimize exposure of PLGA microspheres to acid. This was achieved as demonstrated by release and bioactivity data where alkaline phosphatase released from chitosan/microsphere channels followed a profile and bioactivity similar to those of free floating microspheres.

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“…7,41 In addition, although the smaller particles tend to cause undesirable burst releases, 42 larger particles can pose problems in microcirculation due to their inability to travel through small blood capillaries. The capability to segregate polydisperse particles into different size ranges is highly useful for in vivo drug delivery studies and organ-specific applications.…”

Section: Discussionmentioning

confidence: 99%

Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation

et al. 2017

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Efficient separation of sub-micrometer synthetic or biological components is imperative in particle-based drug delivery systems and purification of extracellular vesicles for point-of-care diagnostics. Herein, we report a novel phenomenon in spiral inertial microfluidics, in which the particle transient innermost distance (D inner ) varies with size during Dean vortices-induced migration and can be utilized for small microparticle (MP) separation; aptly termed as high-resolution Dean flow fractionation (HiDFF). The developed technology was optimized using binary bead mixtures (1-3 μm) to achieve~100-to 1000-fold enrichment of smaller particles. We demonstrated tunable size fractionation of polydispersed drug-loaded poly(lactic-co-glycolic acid) particles for enhanced drug release and anti-tumor effects. As a proof-of-concept for microvesicles studies, circulating extracellular vesicles/ MPs were isolated directly from whole blood using HiDFF. Purified MPs exhibited well-preserved surface morphology with efficient isolation within minutes as compared with multi-step centrifugation. In a cohort of type 2 diabetes mellitus subjects, we observed strong associations of immune cell-derived MPs with cardiovascular risk factors including body mass index, carotid intima-media thickness and triglyceride levels (Po0.05). Overall, HiDFF represents a key technological progress toward highthroughput, single-step purification of engineered or cell-derived MPs with the potential for quantitative MP-based health profiling. NPG Asia Materials (2017) 9, e434; doi:10.1038/am.2017.175; published online 29 September 2017 INTRODUCTIONEnabling technologies for continuous, size-based separation of submicrometer engineered or biological components are highly desirable in clinical applications, such as particle-based drug delivery systems 1 and the purification of extracellular vesicles in clinical diagnostics. 2 In microparticle fabrication, conventional 'bottom-up' self-assembly emulsification techniques yield a broad particle size distribution, which can affect the drug release kinetics and biotransport in blood. 3,4 Although well-controlled and monodisperse particles can be produced by 'top-down' approaches using specific lithographic techniques 5,6 and microfluidics, 7,8 microfabricated particles are prone to damage during mechanical harvesting, a problem further aggravated at the smaller/nanoscale level. Similarly, microfluidic synthesis of drug-loaded polymeric particles requires compatible drug/surfactant chemistry with additional steps to remove solvent prior use. Developing novel tools to achieve tunable size fractionation of polydispersed synthetic particles would enable optimal biodistribution and controlled drug release. Such technologies also facilitate physical isolation of smaller biological targets (o2 μm) including platelets, microbes and extracellular vesicles in a label-free manner for unbiased downstream analysis.

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Effect of mean diameter and polydispersity of PLG microspheres on drug release: Experiment and theory

Cited by 92 publications

References 23 publications

Mucuna gum microspheres for oral delivery of glibenclamide: In vitro evaluation

Mucuna gum microspheres for oral delivery of glibenclamide: In vitro evaluation

Design of Protein‐Releasing Chitosan Channels

Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation

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