Does PLGA microparticle swelling control drug release? New insight based on single particle swelling studies

Gasmi, H.; Danède, Florence; Siepmann, Juergen; Siepmann, Florence

doi:10.1016/j.jconrel.2015.06.039

Cited by 84 publications

(49 citation statements)

References 23 publications

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“…The onset of microsphere swelling coincides with the onset of the second drug release phase of RG503H microspheres and persisted during the remainder of the drug release period. Although a significant particle size change has been reported for PLGA microspheres at the onset of the second rapid drug release phase, the water uptake was not quantified in this study [14]. In the current study, we were able to quantify the amount of water uptake by the microspheres as they were embedded in the PVA hydrogels and the hydrogels only absorbed water during the initial fast equilibrium phase.…”

Section: Discussionmentioning

confidence: 64%

“…The coincidence between the drug release profile and water uptake for both microsphere formulations indicates swelling as a possible contributing factor to drug release from both formulations. Increased osmotic pressure due to accumulation of degradation products as well as polymer matrix plasticization have been suggested as contributing factors to microsphere swelling [14]. From the current investigation, the internal structure changes ( i.e.…”

Section: Discussionmentioning

confidence: 76%

“…However, the method used by these researchers which involved measuring filtered wet microspheres may have resulted in significant error due to adsorbed water on the microsphere surfaces. More recent findings have indicated that microsphere swelling with significant volume increase coincides with the onset of the second drug burst release phase [13, 14]. Microsphere swelling is possibly a result of polymer chain relaxation due to elevated temperature and increased osmotic pressure resulting from accumulation of dissolved drug and degradation species [15].…”

Section: Introductionmentioning

confidence: 99%

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Seeing is believing, PLGA microsphere degradation revealed in PLGA microsphere/PVA hydrogel composites

Sun

Papadimitrakopoulos

et al. 2016

Journal of Controlled Release

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The aim of this study was to understand the polymer degradation and drug release mechanism from PLGA microspheres embedded in a PVA hydrogel. Two types of microspheres were prepared with different molecular weight PLGA polymers (approximately 25 and 7 kDa) to achieve different drug release profiles, with a 9-day lag phase and without a lag phase, respectively. The kinetics of water uptake into the microspheres coincided with the drug release profiles for both formulations. For the 25 kDa microspheres, minimal water uptake was observed in the early part of the lag phase followed by substantial water uptake at the later stages and in the drug release phase. For the 7 kDa microspheres, water uptake occurred simultaneously with drug release. Water uptake was approximately 2–3 times that of the initial microsphere weight for both formulations. The internal structure of the PLGA microspheres was evaluated using low temperature scanning electron microscopy (cryo-SEM). Burst drug release occurred followed by pore forming from the exterior to the core of both microspheres. A well-defined hydrogel/microsphere interface was observed. For the 25 kDa microspheres, internal pore formation and swelling occurred before the second drug release phase. The surface layer of the microspheres remained intact whereas swelling, and degradation of the core continued throughout the drug release period. In addition, microsphere swelling reduced glucose transport through the coatings in PBS media and this was considered to be a as a consequence of the increased thickness of the coatings. The combination of the swelling and microdialysis results provides a fresh understanding on the competing processes affecting molecular transport of bioanalytes (i.e. glucose) through these composite coatings during prolonged exposure in PBS.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

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Seeing is believing, PLGA microsphere degradation revealed in PLGA microsphere/PVA hydrogel composites

Sun

Papadimitrakopoulos

et al. 2016

Journal of Controlled Release

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“…42 PLGA degrades rapidly at low pH because of the acidcatalyzed degradation of its ester backbone. 43 Thus, stability in acidic environments constitutes an important criterion in evaluating the potential of PLGA-based nanocarriers for chemotherapy. In addition, PLGA NPs degrade via ester hydrolysis, which is accelerated in acidic conditions, 14 whereas PEO-based micelles are reportedly stable in acidic environments.…”

Section: Polydot Degradationmentioning

confidence: 99%

Micelle-templated, poly(lactic-<em>co</em>-glycolic acid) nanoparticles for hydrophobic drug delivery

Nabar¹,

Mahajan²,

Calhoun³

et al. 2018

IJN

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Purpose Poly(lactic- co -glycolic acid) (PLGA) is widely used for drug delivery because of its biocompatibility, ability to solubilize a wide variety of drugs, and tunable degradation. However, achieving sub-100 nm nanoparticles (NPs), as might be desired for delivery via the enhanced permeability and retention effect, is extremely difficult via typical top-down emulsion approaches. Methods Here, we present a bottom-up synthesis method yielding PLGA/block copolymer hybrids (ie, “PolyDots”), consisting of hydrophobic PLGA chains entrapped within self-assembling poly(styrene- b -ethylene oxide) (PS- b -PEO) micelles. Results PolyDots exhibit average diameters <50 nm and lower polydispersity than conventional PLGA NPs. Drug encapsulation efficiencies of PolyDots match conventional PLGA NPs (ie, ~30%) and are greater than those obtained from PS- b -PEO micelles (ie, ~7%). Increasing the PLGA:PS- b -PEO weight ratio alters the drug release mechanism from chain relaxation to erosion controlled. PolyDots are taken up by model glioma cells via endocytotic mechanisms within 24 hours, providing a potential means for delivery to cytoplasm. PolyDots can be lyophilized with minimal change in morphology and encapsulant functionality, and can be produced at scale using electrospray. Conclusion Encapsulation of PLGA within micelles provides a bottom-up route for the synthesis of sub-100 nm PLGA-based nanocarriers with enhanced stability and drug-loading capacity, and tunable drug release, suitable for potential clinical applications.

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“…The drug “has to find its way” out of the dosage form to be released. Different types of physicochemical processes can be involved in the control of the resulting drug release rate, such as drug dissolution, drug diffusion, polymer degradation, polymer swelling, and osmotic effects to mention just a few.…”

Section: Introductionmentioning

confidence: 99%

Towards a better understanding of the release mechanisms of caffeine from PLGA microparticles

Tamani

Hamoudi

Danède

et al. 2019

J of Applied Polymer Sci

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Poly(lactic‐co‐glycolic acid) (PLGA)‐based microparticles can be successfully used to control the release rate of a drug and optimize the therapeutic efficacy of a medical treatment. However, the underlying drug release mechanisms can be complex and are often not fully understood. This renders system optimization cumbersome. In this study, differently sized caffeine‐loaded PLGA microparticles were prepared and the swelling and drug release behaviors of single microparticles were monitored upon exposure to phosphate buffer pH 7.4. Ensembles of microparticles were characterized by X‐ray diffraction, differential scanning calorimetry, scanning electron microscopy, gel permeation chromatography, and optical microscopy. The observed triphasic drug release patterns could be explained as follows. The initial burst release can be attributed to the dissolution of tiny drug crystals with direct surface access. The subsequent second drug release phase (with an about constant release rate) could be attributed to the release of drug crystals in regions, which undergo local swelling. The third release phase (again rapid, leading to complete drug exhaust) could be explained by substantial polymer swelling throughout the systems. Once a critical polymer molecular weight is reached, the PLGA chains are sufficiently hydrophilic, insufficiently entangled and the osmotic pressure created by water soluble degradation products attracts high amounts of water into the system. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48710.

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Does PLGA microparticle swelling control drug release? New insight based on single particle swelling studies

Cited by 84 publications

References 23 publications

Seeing is believing, PLGA microsphere degradation revealed in PLGA microsphere/PVA hydrogel composites

Seeing is believing, PLGA microsphere degradation revealed in PLGA microsphere/PVA hydrogel composites

Micelle-templated, poly(lactic-<em>co</em>-glycolic acid) nanoparticles for hydrophobic drug delivery

Towards a better understanding of the release mechanisms of caffeine from PLGA microparticles

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