ABSTRACT
The present investigation was envisaged to develop liposomal formulation for efficacious and targeted delivery of epidermal growth factor receptor (EGFR) inhibitor (erlotinib) against pancreatic cancer. The marketed formulations bearing current EGFR inhibitors exhibit serious adverse effects including severe skin, hemolytic and gastrointestinal toxicity. To address the obstacles, we have developed the liposomal formulation, by ether injection method, comprising erlotinib, a tyrosine kinase EGFR inhibitor, proposed to be targeted through enhanced permeability and retention effect (EPR) effect against pancreatic cancer. On succeeding, the liposomes were characterized for various pharmaceutical attributes. The developed liposomes found to sustain a particle size of 121 ± 10.7 nm, whereas PDI of 0.22 ± 0.01 with the surface charge value of -33.7 ± 2.30 mV. The entrapment efficiency and drug loading were found to be 82.60 and 15.89 (%w/w), respectively. The hemolysis study suggested that the developed formulation was safer compared with native drug solution. The proof of concept for enhanced efficacy and decreased toxicity has been established through in vitro assays. The IC50 for free erlotinib and formulation was found to be 2.0 ± 0.3 µg/ml and 1.1 ± 0.1 µg/ml, respectively. The effectivity was evident by cellular uptake study and apoptosis, whereas cell cycle arrest study indicated that erlotinib arrests the G0/G1 phase of cell cycle. Further the erlotinib-asolectin liposomal formulation enhanced cytotoxicity in PANC-1 cells at relatively low dose, proving to be an alternative for current chemotherapeutics against pancreatic cancer.
Subject(s)
Liposomes , Pancreatic Neoplasms , Humans , Erlotinib Hydrochloride/pharmacology , Cell Line, Tumor , ErbB Receptors/metabolism , Protein Kinase Inhibitors/pharmacology , Pancreatic NeoplasmsSubject(s)
Antineoplastic Agents , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Antineoplastic Agents/adverse effects , Benzamides , Humans , Imatinib Mesylate/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/chemically induced , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapySubject(s)
Lymphohistiocytosis, Hemophagocytic , Lymphoma, T-Cell, Cutaneous , Lymphoma, T-Cell , Panniculitis , Skin Neoplasms , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphoma, T-Cell/complications , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell, Cutaneous/diagnosis , Panniculitis/diagnosis , Panniculitis/drug therapy , Panniculitis/etiology , Skin Neoplasms/drug therapyABSTRACT
Acanthosis nigricans is associated with numerous systemic disorders. These include endocrinological conditions such as, diabetes, acromegaly, Cushing's syndrome, thyroid dysfunction, as well as metabolic abnormalities like obesity and polycystic ovarian disease. Its association with visceral malignancy is known. Moreover, Acanthosis nigricans is known to be a cutaneous marker of insulin resistance (IR) and hyperinsulinemia. The primary aim of this study was to study clinical and histopathological patterns of acanthosis nigricans and its correlation with dermoscopic patterns and treatment implications. 103 patients clinically diagnosed as acanthosis nigricans were enrolled in the study. Clinical evaluation, dermoscopy, and skin biopsy was done for histopathological evaluation. Consistency was observed in the changes seen on dermoscopy with clinical and histopathological findings. Common dermoscopy findings were Crista Cutis, Sulcus Cutis, Papillary projections, hyperpigmented dots, crypts, and blotching Dermoscopic findings can be correlated with histopathological features. Dermoscopy allows visualization on higher magnification which helps to pick up subtle changes which are not visible to naked eye. Dermoscopy can be a useful tool to distinguish acanthosis nigricans from other pigmentary disorders in patients who are not willing for histopathological examination and helps in treatment making decisions.