On the importance and mechanisms of burst release in matrix-controlled drug delivery systems

Huang, Xiao; Brazel, Christopher S.

doi:10.1016/s0168-3659(01)00248-6

Cited by 1,551 publications

(1,073 citation statements)

References 48 publications

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“…One of the biggest problems with burst release is that it cannot be well controlled. 23 Figure 8 shows a convex, concave and burst followed by zero order release profile all calculated using the mathematical model. The convex release profile was obtained by using microspheres of 75µm in radius with a uniform drug loading of 400 mol/m 3 .…”

Section: Design Of Microspheres To Achieve Desired Profile Of Drug Rementioning

confidence: 99%

A Mechanistic Model for Acidic Drug Release Using Microspheres Made of PLGA 50:50

Sevim

Pan

2016

Mol. Pharmaceutics

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Polyester microspheres are extensively studied for controlled release drug delivery devices, and many models have been developed to describe drug release from the bulk polymer.However, the interaction between drugs and polymers is ignored in most of the existing mathematical models. This paper presents a mechanistic model which captures the interplay between acidic drugs and bioresorbable polyesters. The model considers the autocatalytic effect on polymer degradation arising from carboxylic acid end groups of oligomers and drug molecules. Hence, the enhancing effect of acidic drug on the rate of degradation was fully considered. On the other hand the drug release from polyester microspheres is controlled by drug diffusion from polymer matrix. The drug diffusion coefficient depends strongly on the level of degradation of the polymer. This effect is also included in the model. It is shown that the model can effectively predict experimental data in the literature for both polymer degradation and drug release. Furthermore the model is used to design different systems of microspheres which release drugs with either a zero order profile or burst followed by zero order release profile.

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Section: Design Of Microspheres To Achieve Desired Profile Of Drug Rementioning

confidence: 99%

A Mechanistic Model for Acidic Drug Release Using Microspheres Made of PLGA 50:50

Sevim

Pan

2016

Mol. Pharmaceutics

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“…Proteins that are either loosely associated with the surface or embedded in the surface layer are responsible for the burst release (Sah et al, 1994;O'Hagan et al, 1994;Igartua et al, 1997;Rafati et al, 1997). Second, morphology of the microparticles causes initial burst: The drugs escape from the polymeric matrices through the pores and cracks that form during the microparticle fabrication process (Huang and Brazel, 2001;Yang et al, 2001).…”

Section: Causes Of Initial Burst Releasementioning

confidence: 99%

“…In this way, the protein instability issue is closely related to the incomplete release issue. It is also frequently seen that many controlled release formulations including protein-loaded microparticles release a large bolus of drugs before they can reach a stable release rate (i.e., burst release or initial burst) (Huang and Brazel, 2001). In most cases, the burst release is an ineffective form of drug usage from both therapeutic and economic standpoints.…”

Section: Introductionmentioning

confidence: 99%

Control of encapsulation efficiency and initial burst in polymeric microparticle systems

2004

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Initial burst is one of the major challenges in protein-encapsulated microparticle systems. Since protein release during the initial stage depends mostly on the diffusional escape of the protein, major approaches to prevent the initial burst have focused on efficient encapsulation of the protein within the microparticles. For this reason, control of encapsulation efficiency and the extent of initial burst are based on common formulation parameters. The present article provides a literature review of the formulation parameters that are known to influence the two properties in the emulsion-solvent evaporation/extraction method. Physical and chemical properties of encapsulating polymers, solvent systems, polymer-drug interactions, and properties of the continuous phase are some of the influential variables. Most parameters affect encapsulation efficiency and initial burst by modifying solidification rate of the dispersed phase. In order to prevent many unfavorable events such as pore formation, drug loss, and drug migration that occur while the dispersed phase is in the semi-solid state, it is important to understand and optimize these variables.

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“…3 3 , n undetermined number of Ru4PySH that interact with AuNPs Fig. 4 Time-dependent NO release from Ru-4PySH and AuNPs-{Ru-4PySH} n (5 μmol/ L) in Krebs solution at pH 7.4 in the presence of the aortic rings Our work indicates that the coupling of AuNPs with Ru4PySH contributes to reduce the termed "burst release" [33], characterized by an initial large bolus of NO released before its rate reaches a stable profile. Consequently, time-course for vascular relaxation induced by AuNPs-{Ru-4PySH} n also was increased as compared to Ru-4PySH.…”

Section: Resultsmentioning

confidence: 75%

Gold nanoparticle modifies nitric oxide release and vasodilation in rat aorta

et al. 2014

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Nitric oxide (NO) plays an important role on several biological functions. Recently, it has been reported the possibility of modifying the NO release profile from the NO donors through its coupling to gold nanoparticles (AuNPs). Thus, AuNPs were synthesized and they were exposed to the NO donor ruthenium complex Cis-[Ru(bpy) 2 (NO)(4PySH)].(PF6) 3 termed (Ru-4PySH)-forming AuNPs-{Ru-4PySH} n cluster. Our results indicate that AuNPs do not modify the maximum effect (ME) and potency (pD 2 ) in the vasodilation induced by Ru-4PySH. Both complexes induce similar vascular relaxation in concentration-dependent way. However, the NO released from the complex AuNPs-{Ru-4PySH} n is lower than Ru-4PySH. Both complexes release only NO 0 specie, but AuNPs-{Ru-4PySH} n releases NO in constant way and exclusively in the extracellular medium. In time-course, Ru-4Py-SH was faster than AuNPs-{Ru-4PySH} n in inducing the maximum vasodilation. Inhibition of soluble guanylyl cyclase (sGC) abolished the vasodilation induced by Ru-4PYSH, but not by AuNPs-{Ru-4PySH} n . Nonselective potassium (K + ) channel blocker TEA had no effect on the vasodilation induced by AuNPs-{Ru-4PySH} n , but it reduced the potency to Ru-4PySH. In conclusion, our results suggest that AuNPs can reduce the permeability of NO donor Ru-4PySH due to AuNPs-{Ru-4PySH} n cluster formation. AuNPs reduce NO release, but they do not impair the vasodilator effect induced by the NO donor. Ru-4PySH induces vasodilation by sGC and K + channels activation, while AuNPs-{Ru-4PySH} n activates mainly sGC. Taken together, these findings represent a new pharmacological strategy to control the NO release which could activate selective biological targets.

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On the importance and mechanisms of burst release in matrix-controlled drug delivery systems

Cited by 1,551 publications

References 48 publications

A Mechanistic Model for Acidic Drug Release Using Microspheres Made of PLGA 50:50

A Mechanistic Model for Acidic Drug Release Using Microspheres Made of PLGA 50:50

Control of encapsulation efficiency and initial burst in polymeric microparticle systems

Gold nanoparticle modifies nitric oxide release and vasodilation in rat aorta

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