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. 2022 Mar 10;7(11):9452-9464.
doi: 10.1021/acsomega.1c06796. eCollection 2022 Mar 22.

Hispolon-Loaded Liquid Crystalline Nanoparticles: Development, Stability, In Vitro Delivery Profile, and Assessment of Hepatoprotective Activity in Hepatocellular Carcinoma

Mohammad Javed Ansari  1 , Mahfoozur Rahman  2 , Khalid S Alharbi  3 , Waleed M Altowayan  4 , Ahmed Mahmoud Abdelhaleem Ali  5 , Waleed H Almalki  6 , Md Abul Barkat  7 , Tanuja Singh  8 , Shehla Nasar  9 , Md Habban Akhter  10 , Sarwar Beg  11 , Hani Choudhry  12
Affiliations

Hispolon-Loaded Liquid Crystalline Nanoparticles: Development, Stability, In Vitro Delivery Profile, and Assessment of Hepatoprotective Activity in Hepatocellular Carcinoma

Mohammad Javed Ansari et al. ACS Omega. .

Abstract

The present work describes the development and characterization of liquid crystalline nanoparticles of hispolon (HP-LCNPs) for treating hepatocellular carcinoma. HP-LCNPs were prepared by a top-down method utilizing GMO as the lipid and Pluronic F-127 as the polymeric stabilizer. The prepared formulations (HP1-HP8) were tested for long-term stability, where HP5 showed good stability with a particle size of 172.5 ± 0.3 nm, a polydispersity index (PDI) of 0.38 ± 0.31 nm, a zeta potential of -10.12 mV ± 0.05, an entrapment efficiency of 86.81 ± 2.5%, and a drug loading capacity of 12.51 ± 1.12%. Optical photomicrography and transmission electron microscopy images demonstrated a consistent, low degree of aggregation and a spherical shape of LCNPs. The effect of temperature and pH on the optimized formulation (HP5) indicated good stability at 45 °C and at pH between 2 and 5. In vitro gastrointestinal stability indicated no significant change in the particle size, PDI, and entrapment efficiency of the drug. The drug release study exhibited a biphasic pattern in simulated gastric fluid (pH 1.2) for 2 h and simulated intestinal fluid (pH 7.4) for up to 24 h, while the best fitting of the profile was observed with the Higuchi model, indicating the Fickian diffusion mechanism. The in vivo pharmacokinetic study demonstrated nearly 4.8-fold higher bioavailability from HP5 (AUC: 1774.3 ± 0.41 μg* h/mL) than from the HP suspension (AUC: 369.11 ± 0.11 μg* h/mL). The anticancer activity evaluation revealed a significant improvement in antioxidant parameters and serum hepatic biomarkers (SGOT, SGPT, ALP, total bilirubin, and GGT) in the diethyl nitrosamine-treated group of rats with the optimized LCNP formulation (HP5) vis-à-vis HP suspension.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Particle size distribution of optimized HP5 (A,B), optical photomicrograph of the said formulation (C), and TEM image of the said formulation (D). HP5; hispolon-loaded LCNPs.
Figure 2
Figure 2
(A,B) Effect of temperature on the particle size and PDI of HP5.
Figure 3
Figure 3
(A,B) Effect of pH on the particle size and PDI of HP5.
Figure 4
Figure 4
In vitro release profiles of HP suspension and HP5.
Figure 5
Figure 5
Evaluation of cell viability of HP suspension, HP5, and blank LCNP formulation at various concentrations following incubation with HepG2 cells: (A) for 24 h and (B) for 48 h.
Figure 6
Figure 6
Comparative curves showing pharmacokinetic profile of HP suspension and HP5; data expressed as mean ± S.D. (n = 6).
Figure 7
Figure 7
Biodistribution profiles of HP suspension and HP5 at various time intervals showing relatively enhanced uptake of HP5 by liver and the liver tumor. Statistical significance compared with HP suspension and HP5 (HP-LCNPs): p < 0.01 and p < 0.01. HP; hispolon.
See this image and copyright information in PMC

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