PEGylated-PLGA Nanoparticles Coated with pH-Responsive Tannic Acid–Fe(III) Complexes for Reduced Premature Doxorubicin Release and Enhanced Targeting in Breast Cancer

Abstract

Biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been widely used as delivery vehicles for chemotherapy drugs. However, premature drug release in PLGA NPs can damage healthy tissue and cause serious adverse effects during systemic administration. Here, we report a tannic acid− Fe(III) (Fe III −TA) complex-modified PLGA nanoparticle platform (DOX-TPLGA NPs) for the tumor-targeted delivery of doxorubicin (DOX). A PEGylated-PLGA inner core and Fe III −TA complex outer shell were simultaneously introduced to reduce premature drug release in blood circulation and increase pH-triggered drug release in tumor tissue. Compared to the unmodified NPs, the initial burst rate of DOX-TPLGA NPs was significantly reduced by nearly 2-fold at pH 7.4. Moreover, the cumulative drug release rate at pH 5.0 was 40% greater than that at pH 7.4 due to the pH-response of the Fe III −TA complex. Cellular studies revealed that the TPLGA NPs had enhanced drug uptake and superior cytotoxicity of breast cancer cells in comparison to free DOX. Additionally, the DOX-TPLGA NPs efficiently accumulated in the tumor site of 4T1-bearing nude mice due to the enhanced permeability and retention (EPR) effect and reached a tumor inhibition rate of 85.53 ± 8.77% (1.31-fold versus DOX-PLGA NPs and 3.12-fold versus free DOX). Consequently, the novel TPLGA NPs represent a promising delivery platform to enhance the safety and efficacy of chemotherapy drugs.

Evaluating the effect of synthesis, isolation, and characterisation variables on reported particle size and dispersity of drug loaded PLGA nanoparticles

“…20 For intravenous administration in cancer therapy, PLGA particles of size in the range of 120-150 nm showed improved tumour accumulation and enhanced tumour inhibition rate in mouse breast tumour models (4T1-bearing nude mice). 21 In contrast, submicron particles (500 nm) were demonstrated to be optimal to promote a sustained release of ketamine and hydromorphone for over a month, and are suitable for pain management. 22 The choice of the PLGA nanoparticles (NP) fabrication technique is driven by the application, physico-chemical characteristics of the therapeutic to be encapsulated, and the required size and drug release rate.…”

Peptide nucleic acid delivered by nanoparticles as a gene editing tool: Methods of design, preparation and evaluation

“…The ideal size and shape of NPs differ according to its intended application. For example, PLGA NPs (size range: 120-150 nm) showed enhanced tumor accumulation when administrated intravenously in cancers, however, submicron NPs (500 nm) showed optimal sustained drug release (23,24). The diameter of PLGA PNA/DNA NPs are typically between 250-290 nm as measured by DLS (25) while in other patches the mean diameter was 150 nm 13 .…”

In vitro Antitumor Properties of Fucoidan-Coated, Doxorubicin-Loaded, Mesoporous Polydopamine Nanoparticles

“…The optimal carrier-to-DOX concentration ratio was optimized ( Figure 5 a). The LC increased with the increase in DOX concentration because at increased concentrations, DOX enters the pores of MPDA more easily [ 30 ]. When the concentration of DOX was increased from 25 mg/L to 100 mg/L, the EE decreased from 95.96% ± 1.8% to 58% ± 1.2% because the concentration of DOX exceeded the LC of MPDA.…”