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

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.

Natural Oils Enhance the Topical Delivery of Ketoconazole by Nanoemulgel for Fungal Infections

“…The drawn-off samples were put back into the same volumes of fresh medium. The different time point samples were assayed with a UV–visible spectrophotometer. , Further, the drug release data were applied into the kinetic mathematical models like first order, Higuchi matrix, zero order, Korsemeyer–Peppas, and Hixson–Crowell, as shown below in the equations and a model of good fit was evaluated. , normalHiguchi model : 0.25em F = k × t 1 / 2 zero − normalorder kinetics : 0.25em F = k × t first − normalorder kinetics : 0.25em ln nobreak0em.25em⁡ F = k × t 2 Korsmeyer − normalPeppas model ; 0.25em F = k × t n Hixson–Crowell model: W 0 1 / 3 − W t 1 / 3 = κ t In the above equations (–), F indicates the drug release fraction, “ k ” is a constant, “ t ” is the time, “ n ” is the release exponent, W 0 and W t initial and final drug concentrations, and kappa (κ) represents surface and volume relation.…”

“…55,56 Further, the drug release data were applied into the kinetic mathematical models like first order, Higuchi matrix, zero order, Korsemeyer−Peppas, and Hixson−Crowell, as shown below in the equations and a model of good fit was evaluated. 57,58 = × F k t Higuchi model: Hixson−Crowell model:…”

Design-of-Experiment-Assisted Fabrication of Biodegradable Polymeric Nanoparticles: In Vitro Characterization, Biological Activity, and In Vivo Assessment

“…On the other hand, when 0.5 < n < 1, the drug diffusion from the polymer matrix relates to an anomalous, non-Fickian drug diffusion. Further, n = 1 relates to a non-Fickian, case II (relaxational) transport or zero-order release kinetics and n > 1 relates to a supercase II transport. , …”

A “Trojan Horse” Strategy: The Preparation of Bile Acid-Modifying Irinotecan Hydrochloride Nanoliposomes for Liver-Targeted Anticancer Drug Delivery System Study

“…Modern research focuses on finding effective drug delivery systems that enable the decrease of administration with the purpose of reducing drug toxicity [ 13 , 14 ]. Nanoparticles play an important role in cancer therapy, such as Ansari et al’s prepared hispolon-loaded liquid crystalline nanoparticles, which significantly improved the biological indices associated with liver cancer [ 15 ]; Shnoudeh et al fabricated gold (Au), iron (Fe), and selenium (Se) nanoparticles (NPs) with an excellent biocompatibility [ 16 ]. Liposomes are widely studied nanoparticles, which are lipid bilayers of bubbles encapsulating drugs.…”