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HPMA-PLGA Based Nanoparticles for Effective In Vitro Delivery of Rifampicin

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Abstract

Purpose

Tuberculosis (TB) chemotherapy witnesses some major challenges such as poor water-solubility and bioavailability of drugs that frequently delay the treatment. In the present study, an attempt to enhance the aqueous solubility of rifampicin (RMP) was made via co-polymeric nanoparticles approach. HPMA (N-2-hydroxypropylmethacrylamide)-PLGA based polymeric nanoparticulate system were prepared and evaluated against Mycobacterium tuberculosis (MTB) for sustained release and bioavailability of RMP to achieve better delivery.

Methodology

HPMA-PLGA nanoparticles (HP-NPs) were prepared by modified nanoprecipitation technique, RMP was loaded in the prepared NPs. Characterization for particle size, zeta potential, and drug-loading capacity was performed. Release was studied using membrane dialysis method.

Results

The average particles size, zeta potential, polydispersity index of RMP loaded HPMA-PLGA-NPs (HPR-NPs) were 260.3 ± 2.21 nm, −6.63 ± 1.28 mV, and 0.303 ± 0.22, respectively. TEM images showed spherical shaped NPs with uniform distribution without any cluster formation. Entrapment efficiency and drug loading efficiency of HPR-NPs were found to be 76.25 ± 1.28%, and 26.19 ± 2.24%, respectively. Kinetic models of drug release including Higuchi and Korsmeyer-peppas demonstrated sustained release pattern. Interaction studies with human RBCs confirmed that RMP loaded HP-NPs are less toxic in this model than pure RMP with (p < 0.05).

Conclusions

The pathogen inhibition studies revealed that developed HPR-NPs were approximately four times more effective with (p < 0.05) than pure drug against sensitive Mycobacterium tuberculosis (MTB) stain. It may be concluded that HPR-NPs holds promising potential for increasing solubility and bioavailability of RMP.

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Abbreviations

ACN:

Acetonitrile

ETB:

Ethambutol

HPMA:

N-2-hydroxypropylmethacrylamide co-polymer

HP-NPs:

HPMA-PLGA nanoparticles

HPR-NPs:

Rifampicin loaded HPMA-PLGA nanoparticles

INH:

Isoniazid

MABA:

Microplate Alamar Blue Assay

MTB:

Mycobacterium tuberculosis

MIC:

Minimum inhibitory concentration

NPs:

Nanoparticles

PLGA:

Poly-lactic-co-glycolic acid

PNPs:

Polymeric Nanoparticles

PPB:

Plasma protein binding

PYZ:

Pyrazinamide

RMP:

Rifampicin

STP:

Streptomycin

TB:

Tuberculosis

TEM:

Transmission electron microscopy

WHO:

World Health Organization

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors acknowledge the financial support from the Rajasthan Department of Science and Technlogy, Jaipur India and Department of Science and Technology, New Delhi, India through DST Start up Research Grant (Young Scientists) to Dr. Umesh Gupta. Authors would also like to acknowledge Indian Council of Medical Research (ICMR) for providing facilities at JALMA, Agra, India. The authors declare no competing financial interest.

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Authors and Affiliations

  1. Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan, 305817, India

    Sarita Rani, Avinash Gothwal, Pawan K. Pandey & Umesh Gupta

  2. ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, Uttar Pradesh, 282001, India

    Devendra S. Chauhan, Praveen K. Pachouri & Umesh D. Gupta

Authors
  1. Sarita Rani
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  2. Avinash Gothwal
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  3. Pawan K. Pandey
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  4. Devendra S. Chauhan
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  5. Praveen K. Pachouri
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  6. Umesh D. Gupta
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  7. Umesh Gupta
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Correspondence to Umesh Gupta.

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Highlights

• HPMA (N-2-hydroxypropylmethacrylamide) co-polymer was synthesized and characterized.

• HPMA-PLGA NPs were allowed to self-assemble in order to remove acetonitrile, organic solvent for safety purposes.

• Solubility of RMP was increased 65 folds via HPMA-PLGA hydrophilic co-polymer.

• Overall efficacy of the prepared polymeric nanoparticles against the Mycobacterium tuberculosis was enhanced several folds over the naïve drug RMP.

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Rani, S., Gothwal, A., Pandey, P.K. et al. HPMA-PLGA Based Nanoparticles for Effective In Vitro Delivery of Rifampicin. Pharm Res 36, 19 (2019). https://doi.org/10.1007/s11095-018-2543-x

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