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The PLGA Microspheres Synthesized by a Thermosensitive Hydrogel Emulsifier for Sustained Release of Risperidone

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Abstract

Purpose

Risperidone is an important antipsychotic agent used for treatment of both acute and chronic schizophrenia. The drug has been effective in resolving the disease’s signs while keeping extrapyramidal side effects as low as possible. To achieve a sustained and gradual release of risperidone from PLGA microspheres, we utilized an emulsifying agent; PLGA-PEG-PLGA triblock (M-triblock), instead of PVA (M-PVA), applying ring-opening polymerization of the triblock via supercritical carbon dioxide (scCO2).

Methods

PVA and PLGA-PEG-PLGA (as emulsifiers) were successfully employed to prepare risperidone-loaded PLGA microspheres. The scCO2 and microwave irradiation methods were used to construct PLGA-PEG-PLGA copolymers. The microspheres were subjected to various analyses to determine the particles’ sizes, morphological characteristics, and structure (via XRD) and in vitro drug release kinetics. Drug loading capacity and encapsulation percentage were also determined.

Results

The results showed a mean diameter of 43.34 ± 2.30 µm for M-PVA, and that of the M-triblock was 57.49 ± 1.21 µm. Risperidone encapsulation percentages were 72.8 ± 2.09 for M-PVAs and 73.4 ± 2.41 for the M-triblock. Particle size, risperidone distribution, and drug loading and encapsulation percentages were similar between M-PVAs and the M-triblock. In scanning electron microscopy (SEM), the morphology of the triblock emulsifier was more uniform than PVAs.

Conclusions

The triblock emulsifier showed slower initial drug release than PVAs due to the precipitation of the triblock hydrogel around PLGA microspheres. Overall, the triblock used here can be a good alternative to PVA.

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Abbreviations

PEG:

Polyethylene glycol

PLGA:

Poly lactic-co-glycolic acid

Triblock:

PLGA-PEG-PLGA

M-triblock:

Microsphere via PLGA-PEG-PLGA as an emulsifier

PVA:

Poly(vinyl alcohol)

M-PVA:

Microsphere via PVA as an emulsifier

XRD:

X-ray diffraction

SEM:

Scanning electron microscopy

DCM:

Dichloromethane

FDA:

U.S. Food and Drug Administration

GA:

Glycolide

LA:

D,L-lactide

FID:

Flame ionization detector

GPC:

Gel permeation chromatography

1H-NMR:

Proton-nuclear magnetic resonance

PDI:

Polydispersity index

SEC:

Size exclusion chromatography

A s/A is :

Areasample/Ainternal standard

PBS:

Phosphate buffer solution

THF:

Tetrahydrofuran

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Funding

This work was supported by the grant number 951793 from Mashhad University of Medical Sciences.

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Authors and Affiliations

  1. Pharmaceutical Technology Institute, Nanotechnology Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Mohammadpour

  2. Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Hossein Kamali, Maryam Bagheri, Seyedeh Nesa Rezaeian Shiadeh & Elham Khodaverdi

  3. Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Hossein Kamali & Elham Khodaverdi

  4. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Farzin Hadizadeh

  5. Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Farzin Hadizadeh

  6. School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

    Ali Nazari

  7. Department of Advanced Sciences and Technologies, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

    Fatemeh Oroojalian

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  1. Fatemeh Mohammadpour
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Mohammadpour, F., Kamali, H., Hadizadeh, F. et al. The PLGA Microspheres Synthesized by a Thermosensitive Hydrogel Emulsifier for Sustained Release of Risperidone. J Pharm Innov 17, 712–724 (2022). https://doi.org/10.1007/s12247-021-09544-7

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