pH-Triggered release from surface-modified poly(lactic-co-glycolic acid) nanoparticles

Abstract

SummaryNanoparticles (NP) of poly(lactic-co-glycolic acid) (PLGA) represent a promising biodegradable drug delivery system. We suggest here a two-step release system of PLGA nanoparticles with a pH-tunable polymeric shell, providing an initial pH-triggered step, releasing a membrane-toxic cationic compound. PLGA nanoparticles are coated by polyelectrolytes using the layer-by-layer self-assembly technique, employing poly(acrylic acid) (PAA) as a pH-sensitive component and poly(diallyldimethylammonium chloride) (PDADMAC) as the releasable polycation. The pH during multilayer deposition plays a major role and influences the titration curve of the layer system. The pH-tunability of PAA is intensively investigated with regard to the pH region, in which the particle system becomes uncharged. The isoelectric point can be shifted by employing suitable deposition pH values. The release is investigated by quantitative 1H NMR, yielding a pH-dependent release curve. A release of PDADMAC is initiated by a decrease of the pH value. The released amount of polymer, as quantified by 1H NMR analysis, clearly depends on the pH value and thus on the state of deprotonation of the pH-sensitive PAA layer. Subsequent incubation of the nanoparticles with high concentrations of sodium chloride shows no further release and thus demonstrates the pH-driven release to be quantitative.

Development of a fast and precise method for simultaneous quantification of the PLGA monomers lactic and glycolic acid by HPLC

“…Despite the high interest in PLGA, a convenient method for the quantification of the polymer matrix is still lacking. Usually, the PLGA system is estimated by gravimetric methods after sample lyophilization or, for increasing the sensitivity, by more complex methods like mass spectrometry, nuclear magnetic resonance or other analysis methods [13], [14], [15], [16], [17]. However, these approaches suffer partly from sensitivity, as the pure polymer matrix cannot be quantified selectively or the required equipment for improving the sensitivity is expensive and the quantification is time consuming.…”

Doxorubicin Loaded PLGA Nanoparticle with Cationic/Anionic Polyelectrolyte Decoration: Characterization, and Its Therapeutic Potency

“…During the LBL self-assembly process, the pH value of polyelectrolyte solutions should be considered. The ionization degree of PAA was increased with the increasing pH value, and the protonated degree of PEI could be enhanced with the decreasing pH value [ 38 , 39 ]. Furthermore, both alkaline and acid surroundings accelerated the degradation of PLGA [ 40 ].…”

“…In particular, DOX release of AIDPN at pH 5.5 continued to constantly increase within the 72 h of the experiment until it reached its equilibrium at 63.9%, showing a significantly higher drug release (39.4%) than the corresponding nanoparticles in the physiological solution (pH 7.4). The increased DOX release at pH = 5.5 can be attributed to the higher anionic degree of PAA at pH 7.4 than at pH 5.5 [ 38 , 39 ] with stronger binding affinity to protonated DOX, which resulted in an approximately 1.6 times higher drug release from AIDPN at pH = 5.5 compared to that at pH = 7.4. Due to the additional PAA layer, the release profile of IDPN and AIDPN was significantly different in pH 7.4 PBS but similar in pH 5.5 PBS ( Figure 4 ).…”

A Review of the Structure, Preparation, and Application of NLCs, PNPs, and PLNs

“…Zhang et al [ 65 ] and Sheng et al [ 66 ] prepared PNPs by the double-emulsion evaporation method. PLGA and PLA were used as polymers, and the sizes of the nanoparticles were 188 and 100–200 nm, respectively.…”