Chetan Yewale

Epidermal growth factor receptor targeting in cancer: A review of trends and strategies

The epidermal growth factor receptor (EGFR) is a cell-surface receptor belonging to ErbB family of tyrosine kinase and it plays a vital role in the regulation of cell proliferation, survival and differentiation. However; EGFR is aberrantly activated by various mechanisms like receptor overexpression, mutation, ligand-dependent receptor dimerization, ligand-independent activation and is associated with development of variety of tumors. Therefore, specific EGFR inhibition is one of the key targets for cancer therapy. Two major approaches have been developed and demonstrated benefits in clinical trials for targeting EGFR; monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). EGFR inhibitors like, cetuximab, panitumumab, etc. (mAbs) and gefitinib, erlotinib, lapatinib, etc. (TKIs) are now commercially available for treatment of variety of cancers. Recently, many other agents like peptides, nanobodies, affibodies and antisense oligonucleotide have also shown better efficacy in targeting and inhibiting EGFR. Now a days, efforts are being focused to identify molecular markers that can predict patients more likely to respond to anti-EGFR therapy; to find out combinatorial approaches with EGFR inhibitors and to bring new therapeutic agents with clinical efficacy. In this review we have outlined the role of EGFR in cancer, different types of EGFR inhibitors, preclinical and clinical status of EGFR inhibitors as well as summarized the recent efforts made in the field of molecular EGFR targeting.

Proteins: emerging carrier for delivery of cancer therapeutics.

Introduction: Over the past decades, proteins have emerged as versatile carriers for the diagnosis and treatment of cancer, diabetes, rheumatoid arthritis, and many more diseases. Proteins have gained considerable attention in formulation of several delivery systems for anticancer drugs due to their nontoxic, non-immunogenic, biocompatible and biodegradable nature. Proteins are good candidates for conjugation with drugs as they provide good pharmacokinetics as well as better cancer tissue accumulation. Protein nanoparticulate systems are also of advancing importance owing to their modifiable functionalities and potential applications in various biological fields. The customizable nature of proteins also makes them outstanding carriers as target-specific delivery systems. Areas covered: This review emphasizes on protein conjugates (drug-albumin, drug-gelatin, drug-transferrin, and drug-antibody conjugates), protein nanoparticles (prepared using albumin, gelatin, casein, silk proteins, elastin, and lectins), surface modification of protein nanoparticles (using surfactant, polyethylene glycol, cationic/thermosensitive polymers, folic acid, monoclonal antibodies, and peptides/proteins), and their preclinical and clinical status with respect to cancer therapy. Expert opinion: The major obstacles for commercial success of protein-based delivery are lack of inexpensive as well as quality methods for their preparation and quality control; and if overcome, proteins will stand out as a superior drug-delivery carrier for cancer therapy.

Amphotericin B topical microemulsion: formulation, characterization and evaluation.

The present studies were designed to develop a microemulsion (ME) formulation of Amphotericin B (Amp B) for the treatment of invasive fungal infections. The oil phase was selected on the basis of drug solubility whereas the surfactant and co-surfactant were screened and selected on the basis of their oil solubilizing capacity as well as their efficiency to form ME. Pseudo-ternary phase diagrams were constructed and on the basis of ME existence ranges various formulations of Amp B were developed. The influence of surfactant and co-surfactant mass ratio (Smix) on the ME formation and permeation of ME through excised rat skin was studied. The optimized formulation (ME 7) consisting of 0.1% (w/w) Amp B, 5% (w/w) Isopropyl Myristate and 35% (w/w) Smix (3:1, Tween 80 and Propylene glycol), has shown a globule size of 84.20 ± 2.13 nm, a polydispersity index of 0.164 ± 0.031, pH 7.36 ± 0.02 and conductance of 229.3 ± 1.95 μS. ME 7 exhibited 2-fold higher drug permeation as compared to plain drug solution. Besides this, the formulation was also evaluated for drug content, stability, skin retention, skin sensitivity and anti-fungal activity. In vitro anti-fungal activity in Trichophyton rubrum fungal species have shown that ME7 has higher zone of inhibition and the formulation was found stable at 2-8°C and at room temperature (25 ± 2°C) for the period of three months. The results indicate that, the investigated ME may be used as a promising alternative for Amp B therapy.

Topical Amphotericin B solid lipid nanoparticles: Design and development.

The present work is focused on design and development of topical Amphotericin B solid lipid nanoparticles (SLNs) to improve the therapeutic antifungal activity. Amphotericin B loaded SLNs were prepared by novel solvent diffusion method and were characterized for particle size, zeta potential, drug entrapment, surface morphology, in vitro antifungal activity, ex vivo permeation, retention and skin-irritation. Optimized SLNs were spherical with average size of 111.1±2.2nm, zeta potential of -23.98±1.36mV and 93.8±1.8% of drug entrapment. Characterization of Amphotericin B SLNs by differential scanning calorimetry, Fourier transform infrared spectroscopy and Powder X-ray diffraction studies revealed absence of interaction between Amphotericin B and lipid. Amphotericin B is well dispersed in the lipid matrix without any crystallization. The SLNs were lyophilized with and without cryoprotectants to evaluate the stability and it was observed that the particle size of the SLNs significantly increased in SLN formulations lyophilized without cryoprotectant. The optimized SLN 5 formulation exhibited 2 fold higher drug permeation as compared to plain drug dispersion and higher zone of inhibition in Trichophyton rubrum fungal species. Formulation was found to be stable at 2-8°C and 25±2°C for the period of three months. Results of present study indicate that SLNs are suitable carriers for entrapment of poorly water soluble drugs and for enhancement of therapeutic efficacy of antifungal drug.

Formulation and development of taste masked fast-disintegrating tablets (FDTs) of Chlorpheniramine maleate using ion-exchange resins

Context: Masking of bitter taste of drug for better patient compliance. Objective: The objective of this research was to mask the bitter taste of Chlorpheniramine maleate using cation exchange resins. Materials and methods: Different cation exchange resins were used for taste masking. The drug resin complexes (DRC) were prepared by batch process. Complexes of ion-exchange resin and Chlorpheniramine maleate were prepared by taking drug: resin ratios 1:1, 1:2, 1: 3 and 1:4 (w/w). The optimum drug: resin ratio and the time required for maximum complexation was determined. The drug resinates were evaluated for the drug content, taste, drug release, FTIR, DSC and X-ray diffraction (PXRD). Results and discussion: The X-ray diffraction study confirmed the monomolecularity of entrapped drug in the resin beads. The taste evaluation depicted the successful taste masking of Chlorpheniramine maleate with DRCs. Fast disintegrating tablets (FDTs) were developed depending upon percent complexation, release study at salivary and gastric pH, taste evaluation; Chlorpheniramine maleate: Indion-234 complex of ratio 1:2 was used to develop and formulate FDTs. The drug release of 94.77% in 30 min was observed from FDTs. Conclusion: The Effective taste masking can be obtained from DRC that can be formulated as FDTs for better patient compliance.