HPMA-PLGA Based Nanoparticles for Effective In Vitro Delivery of Rifampicin
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.
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.
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).
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.
KeywordsHPMA (N-2-hydroxypropylmethacrylamide) nanoparticles (NPs) PLGA rifampicin (RMP) solubility tuberculosis (TB)
Rifampicin loaded HPMA-PLGA nanoparticles
Microplate Alamar Blue Assay
Minimum inhibitory concentration
Plasma protein binding
Transmission electron microscopy
World Health Organization
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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