We need our bones: a pH-responsive drug delivery system for perspective microenvironment-driven therapy of osteoporosis

In this study, we report the development of a pH-responsive drug delivery system based on waste-derived zeolite X, functionalised with chitosan as a pH-sensitive linker and loaded with risedronate. Zeolite X was prepared in three ionic forms (Na⁺, Ca²⁺, and Ca²⁺/Mg²⁺) to investigate the influence of cation composition on drug loading, release behaviour, and biological response. Release studies demonstrated a pronounced pH-dependent behaviour, with rapid drug release under acidic conditions (pH 4.0) mimicking osteoclast-mediated bone resorption, and minimal release at physiological pH (7.4). Kinetic analysis indicated diffusion-dominated release in acidic environments, while desorption-controlled behaviour prevailed at neutral pH. The in vitro cytotoxicity assessment confirmed the biological safety of the Na⁺ and Ca²⁺/Mg²⁺ systems. Overall, this work demonstrates a sustainable and tuneable platform for microenvironment-driven, localised osteoporosis therapy.

Abbreviation of the samples: NaX/CaX/Ca/MgX - zeolite X in the the Na, Ca, Ca/Mg forms, CH- chitosan, RIS- risedronate.

BET/
Contains raw BET surface area and porosity analysis reports for all investigated materials (csv or xlsx). Files include adsorption–desorption isotherms and calculated textural parameters.

Cytotoxicity/
Raw biological evaluation data obtained using MC3T3-E1 preosteoblast cells (csv or xlsx).
Live/Dead staining – fluorescence microscopy images used to assess cell viability (tiff).
MTT assay – spreadsheet with absorbance values and calculated cell viability percentages (csv or xlsx).

FTIR_PAS/
Raw FTIR spectra recorded in PAS mode (OMNIC format) for all materials, including:
pristine zeolite-based systems,
chitosan-modified samples,
risedronate-loaded systems.

Release/
Contains the raw spreadsheet file with drug release data used for all kinetic analyses. The file includes time-resolved absorbance values measured under different pH conditions (csv or xlsx).

SEM_EDS/
Raw SEM–EDS mapping data for selected materials. Subfolders correspond to individual samples:
NaXCHRIS
CaXCHRIS
CaMgXCHRIS
Each folder contains:
reference SEM images,
elemental EDS maps (counts) for individual elements (e.g., Na, Ca, Mg, Si, Al, O, P).
All files are provided in original tiff format.

XRD/
Raw X-ray diffraction data for all analyzed samples. For each material, two file types are provided:
text-based diffraction intensity data (for plotting and analysis),
native instrument XRD data files (xrdml and csv).

XRF/
Raw XRF elemental composition results provided as a spreadsheet file. The data were used to determine bulk chemical composition and cation exchange efficiency (xlsx).

General notes
All data are presented without normalization, smoothing, or baseline correction, unless stated otherwise in the manuscript.
File names correspond directly to sample codes used in the publication.
The raw data provided here fully support the figures, tables, and analyses reported in the article.