Chitosan/PLGA Particles for Controlled Release of α-Tocopherol in The GI Tract Via Oral Administration

Murugeshu, Abitha; Astete, Carlos E.; Leonardi, Claudia; Morgan, Timothy W.; Sabliov, Cristina M.

doi:10.2217/nnm.11.44

Cited by 47 publications

(33 citation statements)

References 59 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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“…For example, Arunkumar, Harish Prashanth, and Baskaran (2013) reported that lutein nanoentrapped in chitosan displayed higher bioavailability than unmodified lutein in mice. Poly(lactic-co-glycolic) acid (PLGA) has been used successfully as a biodegradable polymer and is often preferred for NP synthesis because of its well-established safety (Semete et al, 2010) and stability in intestinal environments (Murugeshu, Astete, Leonardi, Morgan, & Sabliov, 2011) as well as its effectiveness as a carrier of hydrophobic compounds (Khalil et al, 2013;Li et al, 2013;Tsai et al, 2011). However, its application with carotenoids has not been reported previously.…”

Section: Introductionmentioning

confidence: 99%

Bioavailability and biodistribution of nanodelivered lutein

et al. 2016

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“…Considering the great potential advantages of the use of chitosan-coated PLGA (CS-PLGA) nanoparticles as carriers, numerous studies have investigated their transport potential in gene, drug, and vaccine delivery, via various administration routes. [16][17][18][19][20][21][22] However, to our knowledge, no study has yet investigated the potential of CS-PLGA nanoparticles for intestinal delivery of exendin-4 or reported the effect of molecular weight and degree of deacetylation on the characteristics of CS-PLGA nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4

Wang

Zhang²,

Jiao³

et al. 2013

IJN

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Background: Exendin-4 is an incretin mimetic agent approved for type 2 diabetes treatment. However, the required frequent injections restrict its clinical application. Here, the potential use of chitosan-coated poly (d,l-lactide-co-glycolide) (CS-PLGA) nanoparticles was investigated for intestinal delivery of exendin-4. Methods and results: Nanoparticles were prepared using a modified water-oil-water (w/o/w) emulsion solvent-evaporation method, followed by coating with chitosan. The physical properties, particle size, and cell toxicity of the nanoparticles were examined. The cellular uptake mechanism and transmembrane permeability were performed in Madin-Darby canine kidney-cell monolayers. Furthermore, in vivo intraduodenal administration of exendin-4-loaded nanoparticles was carried out in rats. The PLGA nanoparticle coating with chitosan led to a significant change in zeta potential, from negative to positive, accompanied by an increase in particle size of ∼30 nm. Increases in both the molecular weight and degree of deacetylation of chitosan resulted in an observable increase in zeta potential but no apparent change in the particle size of ∼300 nm. Both unmodified PLGA and chitosan-coated nanoparticles showed only slight cytotoxicity. Use of different temperatures and energy depletion suggested that the cellular uptake of both types of nanoparticles was energy-dependent. Further investigation revealed that the uptake of PLGA nanoparticles occurred via caveolin-mediated endocytosis and that of CS-PLGA nanoparticles involved both macropinocytosis and clathrin-mediated endocytosis, as evidenced by using endocytic inhibitors. However, under all conditions, CS-PLGA nanoparticles showed a greater potential to be transported into cells, as shown by flow cytometry and confocal microscopy. Transmembrane permeability analysis showed that unmodified and modified PLGA nanoparticles could improve the transport of exendin-4 by up to 8.9-and 16.5-fold, respectively, consistent with the evaluation in rats. Conclusion:The chitosan-coated nanoparticles have a higher transport potential over both free drug and unmodified particles, providing support for their potential development as a candidate oral delivery agent for exendin-4.

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Chitosan/PLGA Particles for Controlled Release of α-Tocopherol in The GI Tract Via Oral Administration

Abstract: In vitro and ex vivo results showed that PLGA and Chi/PLGA nanoparticles were efficiently taken up by the GI tract and could be optimized to deliver α-tocopherol to the intestine and improve its bioavailability.

Cited by 47 publications

References 59 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

Bioavailability and biodistribution of nanodelivered lutein

Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4

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