Abstract
Oleanolic acid (OA), which is a natural pentacyclic terpenoid, has been identified for hepato-protective, nephron-protective and cardio-tonic properties. In contrast, doxorubicin (DOX) is a famous anti-cancer drug but its efficacy is a question mark because of its known cardio-toxicity. We developed a combined nanoliposomal formulation of DOX with OA, as adjuvant, to overwhelm toxic effects of DOX without compromising anticancer activity. The entrapment efficiency and the particle size were brought in limit by the reengineered ethanolic injection method (REIM), without further extrusion. The developed formulations were stable over the study period of two months. A modified HPLC method was employed for the analysis of OA (drug retention time, Tr = 12 ± 1 min). The recovery of OA against spiked plasma samples was more than 90%. MTT assay showed anti-apoptotic synergism against HepG2 cells at non-fixed ratio (combination index, CI < 1). A sustained in vivo drug release of experimental drugs was depicted over 24 h. Histopathological examination and laboratory findings indicated no visible sign of toxicity in the treated mice group against combined delivery. Hence, this combined nanoliposomal formulation was tagged as a safer therapy for the DOX based cancer treatments.
Highlights
Combination anticancer therapy has long been in practice among the clinicians with the objectives to slowdown carcinogenesis and/or to get higher therapeutic efficacy with higher target selectivity via synergism [1]
The liposomal formulations of Oleanolic acid (OA) and DOX were prepared by Thin Film Hydration Method (TFH) method
The higher entrapment efficiency of DOX (EE > 80%) was observed in the single drug formulation (DOX loaded liposomes, DXL), but this EE was reduced to 63.21 ± 4.12% in the ODL formulation (Table 1)
Summary
Combination anticancer therapy has long been in practice among the clinicians with the objectives to slowdown carcinogenesis and/or to get higher therapeutic efficacy with higher target selectivity via synergism [1]. Multiple drugs can suppress the notorious phenomenon “cancer chemoresistance”, which is one of the major cause of the failure of single drug therapy [2]. As this approach getting attention, it is obvious to consider clinical issues, such as choice of drugs, dose adjustment, and mechanisms of synergy in account to identify the most effective combination treatment regimen [3]. Based on above mentioned findings, we were interested to figure out anticancer synergism on selected cell line i.e., HepG2 and KB, while OA and DOX employed in a single carrier system
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