Polymeric nano-encapsulation of 5-fluorouracil enhances anti-cancer activity and ameliorates side effects in solid Ehrlich Carcinoma-bearing mice

Abstract

Biodegradable PLGA nanoparticles, loaded with 5-fluorouracil (5FU), were prepared using a double emulsion method and characterised in terms of mean diameter, zeta potential, entrapment efficiency and in vitro release. Poly (vinyl alcohol) was used to modify both internal and external aqueous phases and shown have a significant effect on nanoparticulate size, encapsulation efficiency and the initial burst release. Addition of poly (ethylene glycol) to the particle matrix, as part of the polymeric backbone, improved significantly the encapsulation efficiency. 5FU-loaded NPs were spherical in shape and negatively charged with a size range of 185-350 nm. Biological evaluation was performed in vivo using a solid Ehrlich carcinoma (SEC) murine model. An optimised 5FU-loaded formulation containing PEG as part of a block copolymer induced a pronounced reduction in tumour volume and tumour weight, together with an improved percentage tumour growth inhibition. Drug-loaded nanoparticles showed no significant toxicity or associated changes on liver and kidney function in tested animals, whereas increased alanine aminotransferase, aspartate aminotransferase and serum creatinine were observed in animals treated with free 5FU. Histopathological examination demonstrated enhanced cytotoxic action of 5FU-loaded nanoparticles when compared to the free drug. Based on these findings, it was concluded that nano-encapsulation of 5FU using PEGylated PLGA improved encapsulation and sustained in vitro release. This leads to increased anti-tumour efficacy against SEC, with a reduction in adverse effects.

<p>Design, Formulation and in vivo Evaluation of Novel Honokiol-Loaded PEGylated PLGA Nanocapsules for Treatment of Breast Cancer</p>

“…The tumor developed as a palpable solid tumor mass which was achieved within 12 days postimplantation in all mice. 12,20 In vivo Anti-Tumor Activity…”

“…Polymeric nanoparticles as a type of colloidal dispersions have been studied for the delivery of bioactive drugs either in pharmaceutical or biotechnological field. [9][10][11][12] Among the different polymeric nanoparticles used, nanocapsules have attracted increased attention. 13,14 Their advantages over classical drug delivery systems are numerous, as they can enhance the aqueous solubility of lipophilic drugs, control its release and increase the bioavailability of different drugs.…”

“…[17][18][19] These polymers are sufficiently stable in vitro and longcirculating in vivo besides they showed high cancer cell internalization by Enhanced Penetration Retention (EPR) effect to achieve passive targeting to tumor site. 12,20 Several attempts are described to develop different carriermediated drug delivery strategies for HK based on nanotechnology. These nano-drug delivery systems include nanosuspension, 21 nanoparticles, [22][23][24] microbubbles, 25 liposomes 26 and polymeric micelles.…”

Polymeric Microsphere Formulation for Colon Targeted Delivery of 5-Fluorouracil Using Biocompatible Natural Gum Katira

“…Chemotherapeutic agent, 5-fluorouracil (5FU) is a potential therapeutic agent for its broad spectrum of activity and clinically used in several solid tumors, viz. colorectal, breast, and head and neck cancers (Haggag et al, 2018). This 5-FU leads to the apoptotic damage of the cancer cells via interfering with thymidylate synthesis (Longley et al, 2003).…”

“…Several limitations of 5-FU restrict its use, which includes variability in oral bioavailability, non-selective bio-distribution, shorter half-life, and unfavorable toxicities. However, formulation scientists have extended their researches towards effective and safe delivery of this drug via the development of nanoemulsion (Shakeel et al, 2014), liposomal delivery (Pentak et al, 2012), polymeric nanoparticle (Haggag et al, 2018), solid-lipid nanoparticle (Patel et al, 2014), etc. A polymeric delivery system using natural gum katira has been pitched in this research, where the drug will be encased in the microsphere to obtain an optimal therapeutic response at the colon.…”