Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier

Makadia, Hirenkumar K.; Siegel, Steven J.

doi:10.3390/polym3031377

Cited by 3,541 publications

(2,770 citation statements)

References 98 publications

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“…These data correspond to other work that indicates that the nature of release profiles in the later time points is due to polymer degradation [27]. The polyesters with higher amounts of lactide exhibit slower degradation rates due to the more hydrophobic characteristic of the lactide monomer with the extra methyl group that hinders water access [28]. Liu and Venkatraman confirmed this by demonstrating that a 75 mol% lactide PLGA ISFI degrades slower than a 50 mol% lactide polymer, and had NMP release profiles that generally agreed with those found here [27].…”

Section: Discussionsupporting

confidence: 90%

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N-methyl pyrrolidone/bone morphogenetic protein-2 double delivery with in situ forming implants

Karfeld-Sulzer

Ghayor

Siegenthaler

et al. 2015

Journal of Controlled Release

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Bone morphogenetic proteins (BMPs) are growth and differentiation factors involved during development in morphogenesis, organogenesis and later mainly in regeneration processes, in particular in bone where they are responsible for osteoinduction. For more than a decade, recombinant human (rh)BMP-2 has been used in the clinic for lumbar spinal fusion at non-physiological high dosages that appear to be causative for side effects, like male sterility. A possible strategy to reduce the effective amount of rhBMP-2 in the clinic is the co-delivery with an enhancer of BMPs' activity. In an earlier study, we showed that N-methylpyrrolidone (NMP) enhances BMP activity in vitro and in vivo. Here we report on the development of a slow and sustained double delivery of rhBMP-2 and NMP via an in situ forming implant based on poly(lactide-co-glycolide). The results showed that the release of NMP can be adjusted by varying the lactide/glycolide ratio and the polymer's molecular weight. The same applied to rhBMP-2, with release rates that could be sustained from two to three weeks. In the in vivo model of a critical size defect in the calvarial bone of rabbits, the implant containing 50 mol% lactide performed better than the one having 75 mol% lactide in terms of defect bridging and extent of bony regenerated area. In situ forming implants for the double delivery of the BMP enhancer NMP and rhBMP-2 appear to be promising delivery systems in bone regeneration. ABSTRACTBone morphogenetic proteins (BMPs) are growth and differentiation factors involved during development in morphogenesis, organogenesis and later mainly in regeneration processes, in particular in bone where they are responsible for osteoinduction. For more than a decade, recombinant human (rh)BMP-2 has been used in the clinic for lumbar spinal fusion at non-physiological high dosages that appear to be causative for side effects, like male sterility. A possible strategy to reduce the effective amount of rhBMP-2 in the clinic is the co-delivery with an enhancer of BMPs' activity. In an earlier study, we showed that N-methylpyrrolidone (NMP) enhances BMP activity in vitro and in vivo. Here we report on the development of a slow and sustained double delivery of rhBMP-2 and NMP via an in situ forming implant based on poly(lactide-co-glycolide). The results showed that the release of NMP can be adjusted by varying the lactide/glycolide ratio and the polymer's molecular weight. The same applied to rhBMP-2, with release rates that could be sustained from two to three weeks. In the in vivo model of a critical size defect in the calvarial bone of rabbits, the implant containing 50 mol% lactide performed better than the one having 75 mol% lactide in terms of defect bridging and extent of bony regenerated area. In situ forming implants for the double delivery of the BMP enhancer NMP and rhBMP-2 appear to be promising delivery systems in bone regeneration.

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Section: Discussionsupporting

confidence: 90%

“…The higher burst rate of polymers with higher lactide content, which agrees with literature [27], can also be attributed to hydrophobicity. Since lactide is more hydrophobic than glycolide [28], the higher amount of lactide will lead to polymers of lower hydrophilicity and a faster transition rate.…”

Section: Discussionmentioning

confidence: 99%

N-methyl pyrrolidone/bone morphogenetic protein-2 double delivery with in situ forming implants

Karfeld-Sulzer

Ghayor

Siegenthaler

et al. 2015

Journal of Controlled Release

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“…Besides the lactic:glycolic acid ratio, the Mn of the PLGA backbone structure is important. From literature it can be concluded that with higher molecular weight slower degradation of the polymer is expected, and therefore a slower release of drugs can be hypothesized (Makadia and Siegel, 2011). This lower degradation and as a consequence slower release, is also however not visible in the first 10 to 20 days.…”

Section: Ova Release From the Particlesmentioning

confidence: 99%

“…Generally, NPs made of PLGA show a biphasic release profile, with an initial burst release followed by a sustained release phase (Makadia and Siegel, 2011). The fast initial burst release is induced by the fast release of protein at or near to the surface of the NP, whereas the sustained release is caused by additional and slower release of protein from the NP polymer matrix through channels.…”

Section: Ova Release From the Particlesmentioning

confidence: 99%

“…The fast initial burst release is induced by the fast release of protein at or near to the surface of the NP, whereas the sustained release is caused by additional and slower release of protein from the NP polymer matrix through channels. The water inside the matrix hydrolyzes the polymer into soluble polymer products, which forms a passage for protein to be released by diffusion and erosion until complete polymer solubilization has occurred (Makadia and Siegel, 2011). Different Mn of PLGA, PEG, PAGE or lactic:glycolic acid ratios within a polymer type had no major influence.…”

Section: Ova Release From the Particlesmentioning

confidence: 99%

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Impact of PEG and PEG- b -PAGE modified PLGA on nanoparticle formation, protein loading and release

Rietscher

Czaplewska

Majdanski

et al. 2016

International Journal of Pharmaceutics

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PLGA nanocapsules as a delivery system for a recombinant LRP‐based therapeutic

Bernert,

Bignoux,

Madhav

et al. 2024

FEBS Open Bio

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Telomerase activity is directly affected by the laminin receptor precursor (LRP) protein, a highly conserved nonintegrin transmembrane receptor, which has been shown to have therapeutic effects in ageing, and age‐related diseases. Recently, it has been found that overexpression of LRP‐FLAG, by plasmid transfection, leads to a significant increase in telomerase activity in cell culture models. This may indicate that upregulation of LRP can be used to treat various age‐related diseases. However, transfection is not a viable treatment strategy for patients. Therefore, we present a nanoencapsulated protein‐based drug synthesised using poly(lactic‐co‐glycolic acid) (PLGA) nanocapsules for delivery of the 37 kDa LRP protein therapeutic. PLGA nanocapsules were synthesised using the double emulsification‐solvent evaporation technique. Different purification methods, including filtration and centrifugation, were tested to ensure that the nanocapsules were within the optimal size range, and the BCA assay was used to determine encapsulation efficiency. The completed drug was tested in a HEK‐293 cell culture model, to investigate the effect on cell viability, LRP protein levels and telomerase activity. A significant increase in total LRP protein levels with a concomitant increase in cell viability and telomerase activity was observed. Due to the observed increase in telomerase activity, this approach could represent a safer alternative to plasmid transfection for the treatment of age‐related diseases.

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Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier

Cited by 3,541 publications

References 98 publications

N-methyl pyrrolidone/bone morphogenetic protein-2 double delivery with in situ forming implants

N-methyl pyrrolidone/bone morphogenetic protein-2 double delivery with in situ forming implants

Impact of PEG and PEG- b -PAGE modified PLGA on nanoparticle formation, protein loading and release

PLGA nanocapsules as a delivery system for a recombinant LRP‐based therapeutic

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