pH-Responsive Nanogels for Site-Specific Drug Delivery: Synthesis, Characterization, and Stimuli-Triggered Release Behavior

Saba Niaz ¹, Sam Au ¹*

This study developed optimized nanogels for precise, pH-responsive drug release, potentially reducing side effects and improving targeted delivery efficiency.

Abstract

Background: Traditional drug delivery systems face limitations such as low solubility, instability, and toxicity, which can impact efficacy and safety. pH-responsive nanogels offer an innovative approach for controlled and targeted drug delivery, particularly for oral administration, by releasing drugs based on environmental pH changes. Objective: This study aimed to synthesize and characterize novel, physically cross-linked pH-responsive nanogels using poly(L-lysine isophthalamide) grafted with decylamine (PLP-NDA) and evaluate their potential as oral drug delivery vehicles. Methods: PLP-NDA nanogels were synthesized using a surfactant-free nanoprecipitation method, combining anionic and amphiphilic properties with hydrophobic segments for stable nanogel formation and drug loading. The nanogels were characterized for particle size, zeta potential, and stability under varied ionic strengths and pH levels. Nile red (NR) was used as a model hydrophobic drug to assess encapsulation efficiency and release profiles in simulated fasted gastric (pH 1.6) and intestinal fluids (pH 6.5). Results: The synthesized PLP-NDA nanogels had an average particle size of 101.3 ± 1.2 nm and a zeta potential of -37.51 ± 3.32 mV, demonstrating stability over 28 days. Encapsulation efficiency of NR was 16.5 ± 2.1%, with a particle size of 124.5 ± 2.1 nm for PLP-NDA-NR nanogels. Drug release studies showed complete release in intestinal fluid (pH 6.5) within 24 hours, while release in gastric fluid (pH 1.6) was 54.0 ± 3.7%. Conclusion: PLP-NDA nanogels exhibit favorable characteristics for pH-triggered drug release, showing stability and efficient drug encapsulation. These nanogels are promising candidates for oral drug delivery systems targeting gastrointestinal applications, with potential for future clinical development.

Keywords: pH-responsive nanogels, Drug delivery systems (DDS), Polymeric hydrogels, Site-specific release, Biocompatible nanocarriers

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