Mechanistic study of hydrolytic erosion and drug release behaviour of PLGA nanoparticles: Influence of chitosan

Jain, Gaurav; Pathan, Shadab A.; Akhter, Sohail; Ahmad, Niyaz; Jain, Neeraj; Talegaonkar, Sushama; Khar, Roop K.; Ahmad, Farhan Jalees

doi:10.1016/j.polymdegradstab.2010.08.015

Cited by 43 publications

(20 citation statements)

References 27 publications

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“…The PLGA control showed a biphasic response as previously reported (76,77) , with an initial burst release followed by a sustained-release period. The addition of chitosan did not alter the release profile but increased the rate of protein release as reported previously (78)(79)(80) . Microparticles containing chit/TPP showed a triphasic release profile with a higher initial rate of release relative to the control.…”

Section: Protein Release From Plga Microparticlessupporting

confidence: 81%

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

et al. 2016

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Age-related macular degeneration (AMD) is the leading cause of certified vision loss worldwide. The standard treatment for neovascular AMD involves repeated intravitreal injections of therapeutic proteins directed against vascular endothelial growth factor, such as ranibizumab. Biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), form delivery vehicles which can be used to treat posterior segment eye diseases, but suffer from poor protein loading and release. This work describes a 'system-within-system', PLGA microparticles incorporating chitosan-based nanoparticles, for improved loading and sustained intravitreal delivery of ranibizumab. Chitosan-N-acetyl-L-cysteine (CNAC) was synthesized and its synthesis confirmed using FT-IR and 1 H NMR. Chitosan-based nanoparticles comprised of CNAC, CNAC/tripolyphosphate (CNAC/TPP), chitosan, chitosan/TPP (chit/TPP) or chit/TPP-hyaluronic acid (chit/TPP-HA) were incorporated in PLGA microparticles using a modified w/o/w double emulsion method. Nanoparticles and final nanoparticles-within-microparticles were characterized for their protein-nanoparticle interaction, size, zeta potential, morphology, protein loading, stability, in vitro release, in vivo anti-angiogenic activity and effects on cell viability. The prepared nanoparticles were 17 -350 nm in size and had zeta potentials of -1.4 to +12 mV. Microscopic imaging revealed spherical nanoparticles on the surface of PLGA microparticles for preparations containing chit/TPP, CNAC and CNAC/TPP. Ranibizumab entrapment efficiency in the preparations varied between 13 -69% and was highest for the PLGA microparticles containing CNAC nanoparticles. This preparation also showed the slowest release with no initial burst release compared to all other preparations. Incorporation of TPP to this formulation increased the rate of protein release and reduced entrapment efficiency. PLGA microparticles containing chit/TPP-HA showed the fastest and near-complete release of ranibizumab. All of the prepared empty particles showed no effect on cell viability up to a concentration of 12.5 mg/mL. Ranibizumab released from all preparations maintained its structural integrity and in vitro activity. The chit/TPP-HA preparation enhanced anti-angiogenic activity and may provide a potential biocompatible platform for enhanced anti-angiogenic activity in combination with ranibizumab. In conclusion, the PLGA microparticles containing CNAC nanoparticles, showed significantly improved ranibizumab loading and release profile. This novel drug delivery system may have potential for improved intravitreal delivery of therapeutic proteins, thereby reducing the frequency, risk and cost of burdensome intravitreal injections.

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Section: Protein Release From Plga Microparticlessupporting

confidence: 81%

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

et al. 2016

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“…The presence of hydrophilic material in the nanoparticles allows fast influx of water molecules and build-up of osmotic pressure within the nanoparticle matrix resulting in a reduction of the lag phase. 36 Fig. 3C was the pH value change of each time point.…”

Section: Biodegradability In Vitromentioning

confidence: 99%

Electrospun poly(l-lactide-co-caprolactone)–collagen–chitosan vascular graft in a canine femoral artery model

Jiang

Wang

et al. 2015

J. Mater. Chem. B

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Poly(L-lactide-co-caprolactone)/collagen/chitosan (P(LLA-CL)/COL/CS) composite grafts were electrospun in this study. Based on the testing results of mechanical properties, biodegradability and in vitro cellular compatibility, the optimal weight ratio of P(LLA-CL) to COL/CS was set as 3:1. In vivo study was further performed in a canine femoral artery model. The results showed that the 3:1 grafts possessed excellent structural integrity, higher patency rate, better endothelial cells (ECs) and smooth muscle cells (SMCs) growth, as well as higher gene and protein expression levels of angiogenesis-related cues than those of grafts based on P(LLA-CL). The findings confirmed that the addition of natural materials such as collagen and chitosan could effectively improve endothelialization, SMCs incursion in the tunica media, and vascular remodeling for tissue engineering.

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“…Some of their advantages are: ease of fabrication, less invasive administration, and less stressful manufacturing conditions for sensitive bioactive molecules [3,4]. The release profile of the entrapped drug depends on its diffusion through the polymer matrix and/or on the matrix degradation/erosion processes [2,5]. For this reason, the degradation of PLGA is an important issue to be considered in controlled drug release systems [6].…”

Section: Introductionmentioning

confidence: 99%

In vitro bulk/surface erosion pattern of PLGA implant in physiological conditions: a study based on auxiliary microsphere systems

et al. 2015

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This work investigates the degradation of PLGA implants in an aqueous medium maintained at physiological pH & 7.4. Two limiting systems are also investigated, which involve the degradation of PLGA microspheres in two different media characterized by: (i) a non-regulated pH, for emulating the autocatalyzed degradation in the implant core; and (ii) a regulated physiological pH, for emulating the uncatalyzed degradation at the implant surface. The degradation experiments were carried out along 40-50 days, and samples withdrawn during this period were characterized by gravimetry, electronic microscopy, and size exclusion chromatography. Experimental results suggest that PLGA implants are degraded according to a time-variant spatial pattern, which depends on the pH of the surrounding medium. Initially, the implants suffered a typically bulk erosion process, governed by the acidification of the implant core; and after breakage of the implant wall, the regulated physiological pH induces a surface erosion process. The two auxiliary microsphere-based experiments were useful to elucidate the degradation phenomena occurring in the PLGA implants. The evolution of the mass loss and the weight-average molecular weight along the degradation can be successfully predicted by simple mathematical models based on first-order kinetics.

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Mechanistic study of hydrolytic erosion and drug release behaviour of PLGA nanoparticles: Influence of chitosan

Cited by 43 publications

References 27 publications

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

Electrospun poly(l-lactide-co-caprolactone)–collagen–chitosan vascular graft in a canine femoral artery model

In vitro bulk/surface erosion pattern of PLGA implant in physiological conditions: a study based on auxiliary microsphere systems

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