Synthesis and Statistical Optimization of Poly (Lactic-Co-Glycolic Acid) Nanoparticles Encapsulating GLP1 Analog Designed for Oral Delivery

Ismail, Ruba; Sovány, Tamás; Gácsi, Attila; Ambrus, Rita; Katona, Gábor; Imre, Norbert; Csóka, Ildikó

doi:10.1007/s11095-019-2620-9

Cited by 37 publications

(27 citation statements)

References 40 publications

(47 reference statements)

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“…The design matrix was produced by software consisted of 09 experiments shown in Table 3 , all the experiments were performed in a random order to reduce the effect of bias and unknown variables in the obtained results. All other parameters (temperature, rate of stirring and time, the ratio organic to aqueous phase and evaporation time) were kept as constant to minimize instability (Kozaki et al., 2017 ; Ismail et al., 2019 ). 2D Contour plot and 3D-response surface plot were created for illustrative representation of the volume of the response.…”

Section: Methodsmentioning

confidence: 99%

Development, optimization, and evaluation of PEGylated brucine-loaded PLGA nanoparticles

et al. 2020

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The application of nanotechnology to drug delivery systems for cancer therapy has progressively received great attention. The most heavily investigated approach is the development of nanoparticles (NPs) utilizing biodegradable and biocompatible polymers such as poly (lactic-co-glycolic acid) (PLGA). These NPs could be further improved by surface modification utilizing a hydrophilic biodegradable polymer such as polyethylene glycol (PEG) to achieve passive targeting. Modified NPs can deliver drugs such as brucine (BRU), which has shown its potential in cancer therapy. The objective of the current investigation was to develop and evaluate the passive targeting of long-circulating PLGA NPs loaded with BRU. NPs were characterized in terms of drug-excipient compatibility studies, including FTIR and DSC; physicochemical evaluations including particle size, zeta potential, morphological evaluation, entrapment efficiency and percentage yield; total serum protein adsorbed onto NP surfaces; and in vitro release of the loaded drug. Factorial design was employed to attain optimal PLGA-loaded NPs. Finally, the in vivo anti-tumor activity of BRU-loaded PLGA NPs was evaluated in tumor-bearing mice. The NPs obtained had smooth surfaces with particle sizes ranged from 94 ± 3.05 to 253 ± 8.7 nm with slightly positive surface charge ranged from 1.09 ± 0.15 to 3.71 ± 0.44 mV. Entrapment of BRU ranged between 37.5 ± 1.8% and 77 ± 1.3% with yields not less than 70.8%. Total protein adsorbed was less than 25.5 mg total protein/1 mg NP. In vitro drug release was less than 99.1% at 168 h. Finally, significant reductions in tumor growth rate and mortality rate were observed for PEG PLGA NP formulations compared to both BRU solution and naked NPs.

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Section: Methodsmentioning

confidence: 99%

Development, optimization, and evaluation of PEGylated brucine-loaded PLGA nanoparticles

et al. 2020

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“…The Lira loaded PLGA NPs were prepared by the double emulsion solvent evaporation method and then lyophilized as described previously [25]. Following the initial risk assessment-based study [26], the Plackett–Burman screening design of the experiment was applied by our research group to optimize the lyophilized Lira loaded PLGA NP formulation regarding four critical quality attributes namely: particle size, polydispersity index, encapsulation efficiency and zeta potential [25]. The optimized formula is shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Lira was analyzed by a reversed phase HPLC (Agilent 1200, San Diego, CA, USA) method that was previously developed and validated in our lab [25]. A Kinetex ® C18 column with dimensions of (5 μm, 150 × 4.6 mm, (Phenomenex, Torrance, CA, USA) was used as the stationary phase.…”

Section: Methodsmentioning

confidence: 99%

Encapsulation in Polymeric Nanoparticles Enhances the Enzymatic Stability and the Permeability of the GLP-1 Analog, Liraglutide, Across a Culture Model of Intestinal Permeability

et al. 2019

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The potential of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) to overcome the intestinal barrier that limits oral liraglutide delivery was evaluated. Liraglutide-loaded PLGA NPs were prepared by the double emulsion solvent evaporation method. In vitro release kinetics and enzymatic degradation studies were conducted, mimicking the gastrointestinal environment. The permeability of liraglutide solution, liraglutide-loaded PLGA NPs, and liraglutide in the presence of the absorption enhancer PN159 peptide was tested on the Caco-2 cell model. Liraglutide release from PLGA NPs showed a biphasic release pattern with a burst effect of less than 15%. The PLGA nanosystem protected the encapsulated liraglutide from the conditions simulating the gastric environment. The permeability of liraglutide encapsulated in PLGA NPs was 1.5-fold higher (24 × 10−6 cm/s) across Caco-2 cells as compared to liraglutide solution. PLGA NPs were as effective at elevating liraglutide penetration as the tight junction-opening PN159 peptide. No morphological changes were seen in the intercellular junctions of Caco-2 cells after treatment with liraglutide-PLGA NPs, confirming the lack of a paracellular component in the transport mechanism. PLGA NPs, by protecting liraglutide from enzyme degradation and enhancing its permeability across intestinal epithelium, hold great potential as carriers for oral GLP-1 analog delivery.

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“…Table I shows some selected papers and its remarks about QbD application in Pharmaceutical industry, Industrial purposes and Optimization using DoE. [96][97][98][99][100][101][102][103][104][105][106][107][108] DoEs have been used in these biotechnological processes for some years, as reported by Mandenius et al [109] in a review paper, in which DoEs are a powerful tool for the optimization of bioprocesses.…”

Section: Quality By Design (Qbd) Design Of Space and Design Of Expermentioning

confidence: 99%

Key information related to quality by design (QbD) applications in analytical methods development

Araujo¹,

Andrade²,

Babos³

et al. 2020

Braz. J. Anal. Chem.

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In this review, quality by design (QbD) initiatives are described as applications for many types of processes, such as in the pharmaceutical industry, biotechnology field, and for analytical methods development. Design space (DS) and design of experiments (DoE) provide useful results for analytical methods development and simulation of advanced processes in traditional manufacturing relationships. The three topics, QbD, DS and DoE are the best way to achieve strong and efficient industrial production.

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Synthesis and Statistical Optimization of Poly (Lactic-Co-Glycolic Acid) Nanoparticles Encapsulating GLP1 Analog Designed for Oral Delivery

Cited by 37 publications

References 40 publications

Development, optimization, and evaluation of PEGylated brucine-loaded PLGA nanoparticles

Development, optimization, and evaluation of PEGylated brucine-loaded PLGA nanoparticles

Encapsulation in Polymeric Nanoparticles Enhances the Enzymatic Stability and the Permeability of the GLP-1 Analog, Liraglutide, Across a Culture Model of Intestinal Permeability

Key information related to quality by design (QbD) applications in analytical methods development

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