BITS Faculty Publications
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Item Formulating ternary inclusion complex of sorafenib tosylate using β-cyclodextrin and hydrophilic polymers: physicochemical characterization and in vitro assessment(Springer, 2022-09) Marathe, Sandhya Amol; Singhvi, GautamSorafenib tosylate (SFNT) is the first-line drug for hepatocellular carcinoma. It exhibits poor solubility leading to low oral bioavailability subsequently requiring intake of large quantities of drug to exhibit desired efficacy. The present investigation was aimed at enhancing the solubility and dissolution rate of SFNT using complexation method. The binary inclusion complex was prepared with β-cyclodextrin (β-CD). The molecular docking studies confirmed the hosting of SFNT into hydrophobic cavity of β-CD, while the phase solubility studies revealed the stoichiometry of complexation with a stability constant of 735.8 M−1. The ternary complex was prepared by combining the SFNT-β-CD complex with PEG-6000 and HPMC polymers. The results from ATR-IR studies revealed no interaction between drug and excipients. The decreased intensities in ATR-IR peaks and changes in chemical shifts from NMR of SFNT in complexes indicate the possibility of SFNT hosting into the hydrophobic cavity of β-CD. The disappearance of SFNT peak in DSC and XRD studies revealed the amorphization upon complexation. The ternary complexes exhibited improved in vitro solubility (17.54 µg/mL) compared to pure SFNT (0.19 µg/mL) and binary inclusion complex (1.52 µg/mL). The dissolution profile of ternary inclusion complex in 0.1 N HCl was significantly higher compared to binary inclusion complex and pure drug. In cytotoxicity studies, the ternary inclusion complex has shown remarkable effect than the binary inclusion complex and pure drug on HepG2 cell lines.Item Exploring temozolomide encapsulated PEGylated liposomes and lyotropic liquid crystals for effective treatment of glioblastoma: in-vitro, cell line, and pharmacokinetic studies(Elsevier, 2023-05) Singhvi, Gautam; Roy, AniruddhaTemozolomide (TMZ) is one of the best choices for treating glioblastoma. However, due to the short plasma half-life, only 20–30 % brain bioavailability can be achieved using traditional formulations. In the present study, PEGylated liposomes and lyotropic liquid crystals (LLCs) were developed and investigated to prolong the plasma circulation time of TMZ. Industrially feasible membrane extrusion and modified hot melt emulsification techniques were utilized during the formulation. Liposomes and LLCs in the particle size range of 80–120 nm were obtained with up to 50 % entrapment efficiency. The nanocarriers were found to show a prolonged release of up to 72 h. The cytotoxicity studies in glioblastoma cell lines revealed a ∼1.6-fold increased cytotoxicity compared to free TMZ. PEGylated liposomes and PEGylated LLCs were found to show a 3.47 and 3.18-fold less cell uptake in macrophage cell lines than uncoated liposomes and LLCs, respectively. A 1.25 and 2-fold increase in the plasma t1/2 was observed with PEGylated liposomes and PEGylated LLCs, respectively, compared to the TMZ when administered intravenously. Extending plasma circulation time of TMZ led to significant increase in brain bioavailability. Overall, the observed improved pharmacokinetics and biodistribution of TMZ revealed the potential of these PEGylated nanocarriers in the efficient treatment of glioblastoma.Item Nanoscale Pluronic® micellar templates with varying %EO content for controlled drug release and cytotoxicity(Elsevier, 2023-08) Roy, Aniruddha; Singhvi, GautamThis study investigates the self-assembly in ethylene oxide (EO)-propylene oxide (PO)-based block copolymers (BCPs) with various molecular features like molecular weight, EO/PO ratio, HLB (Hydrophobic lipophilic balance) in aqueous solution environment. Our BCP solution systems exhibit significant changes in solution behaviour that showed micellization, micelle growth/ transition, and progressively phase separation (2ϕ), all of which are well explained by clear solution, blue point (BP) and cloud Point (CP) respectively. The solubilization of the highly hydrophobic anticancer drug-Quercetin (QCT) in such BCPs is examined using UV–Visible spectroscopy. The spectral findings inferred the dissolution capability of QCT in the examined copolymeric micellar systems in terms of drug loading efficiency (DL%), encapsulation efficiency (EE%), partition coefficient (P), and standard free energy of solubilization (ΔGo). Amongst the varied tested BCPs, it was observed that Pluronics® P123 and F127 exhibited an enhanced QCT solubilization capability than others and is explained in terms of hydrophobicity and hydrophilicity. The micellar size distribution profile expressed as hydrodynamic diameter (Dh) was determined for QCT-loaded and QCT-unloaded BCP micelles employing dynamic light scattering (DLS). The drug release profile was fitted employing various kinetic models, allowing this study to serve as an excellent foundation for QCT delivery. Reversed-phase High-performance liquid chromatography (HPLC) system determined the retention period in the QCT-loaded micelle while the structural alterations involved in Pluronics®-QCT system is inferred using small-angle neutron scattering (SANS). Fourier transform infrared spectroscopy (FT-IR) depicted the compatibility between Pluronics® and QCT which was validated further from the evaluated optimum descriptors using Gaussian 09 computational simulation framework. It was discovered that the QCT-loaded micelles exhibited a greater anticancer effect than free drug when tested in vivo on cancer cells. The anticancer activity of QCT-loaded F127 micelles was determined to be the strongest. Thus, the current study on QCT solubilization in Pluronics® will benefit considerably from its investigated outcomes.Item Nanocarriers as Potential Targeted Drug Delivery for Cancer Therapy(Springer, 2020-01) Singhvi, GautamCancer is a disease characterized by the uncontrolled growth of cells and is the leading cause of death worldwide with an incidence of 11 million new cases each year. Nanotechnology-based drug delivery systems have received much attention for cancer treatment. Nanocarriers are the delivery systems which are prepared by alteration of the size (1–1000 nm) and shape of a material to the nano-range level. Nanocarriers are prepared by utilizing natural, polymeric, inorganic magnetic silica-based materials. Various nanocarriers including liposomes, solid lipid nanoparticles, polymeric nanoparticles, dendrimers, magnetic nanoparticles, and other inorganic nanoparticles have been investigated for diagnostic, therapeutic, and drug targeting in cancer therapy. Nanocarriers act as a cancer-specific drug delivery or diagnostic agent by inherent passive targeting mechanism or adopted active targeting strategies by altering the surface properties with specific ligands. Targeted nanoparticulate systems increase the accumulation of the chemotherapeutic agent in the tumor tissue and reduce the toxicity to healthy cells. Nanocarriers extend the drug release for a longer duration and protect the drug from degradation. Nanocarriers are also proven effective for improving the pharmacokinetics of poorly soluble hydrophobic drugs by solubilizing or permeating them through lipophilic biological barriers.