Natural clinoptilolite and its functionalization: From limited adsorption to tailored performance for pharmaceutical use

Clinoptilolite is a natural microporous aluminosilicate whose structure underly unique physicochemical properties. These properties support its growing use in medical and pharmaceutical applications. Clinoptilolite has a high surface area and a high ion exchange capacity exploited in many medical applications. Recently, its selective adsorption properties have prompted researchers to study its potential for controlled or targeted drug delivery. In this particular field of application its unmodified, naturally occurring form showed limitations due to its hydrophilicity and small pore size. This is why the natural clinoptilolite mainly shows transient uptake of small or polar drug molecules and is not appropriate for delivery of larger or nonpolar pharmaceutical compounds. The presented review provides a summarized overview of the clinoptilolite physical-chemical properties relevant for its potential drug delivery properties and examines various strategies used to modify the clinoptilolite surface with different organic and inorganic agents. One large portion of studies have provided data on usage of surfactants, chitosan, amine-containing polymers, and green-synthesized nanoparticles for improvement of the clinoptilolite adsorption capacity. Therapeutic functionality of clinoptilolite has been achieved by these surface modifications, i.e. chitosan modified clinoptilolite enabled targeted delivery and wound healing applications. Nanoparticles usage for surface modification, i.e. CaO and MgO were also successfully tested for sustained 5-fluorouracil release in colon cancer therapy. Moreover, the clinoptilolite surface has been successfully functionalized with antioxidant and enzymatic agents. In summary, modifications of the clinoptilolite surface are a growing area of research for obtaining versatile platforms for controlled drug delivery and advanced therapeutic systems. Some of the fields that might benefit the most are oncology and wound care. • Zeolite clinoptilolite are exceptional ion-exchangers with prominent adsorption properties that arise from its porous aluminosilicate framework and high specific surface area • The selectivity of on-exchange in clinoptilolite depends on cation charge, size, and the Si/Al ratio where the higher ratios favour adsorption of larger and less hydrated cations • The microporous structure of clinoptilolite restricts adsorption for molecules larger than ∼0.4 nm, limiting its usage as a drug carrier for larger pharmaceutical compounds • Surface acidity and hydrophilicity of clinoptilolite depends on the Si/Al ratio and oxygen-based adsorption sites • Chemical surface modifications, including acid or surfactant treatments, can enhance clinoptilolite’s ion-exchange capacity and hydrophobicity and improve adsorption efficiency for nonpolar or drug-like molecules.