Abstract

Inorganic diatomite nanoparticles (DNPs) have gained increasing interest as drug delivery systems due to their porous structure, long half-life, thermal and chemical stability. Gold nanoparticles (AuNPs) provide DNPs with intriguing optical features that can be engineered and optimized for sensing and drug delivery applications. In this work, we combine DNPs with gelatin stabilized AuNPs for the development of an optical platform for Galunisertib delivery. To improve the DNP loading capacity, the hybrid platform is capped with gelatin shells of increasing thicknesses. Here, for the first time, full optical modeling of the hybrid system is proposed to monitor both the gelatin generation, degradation, and consequent Galunisertib release by simple spectroscopic measurements. Indeed, the shell thickness is optically estimated as a function of the polymer concentration by exploiting the localized surface plasmon resonance shifts of AuNPs. We simultaneously prove the enhancement of the drug loading capacity of DNPs and that the theoretical modeling represents an efficient predictive tool to design polymer-coated nanocarriers.

Highlights

  • Colorectal cancer (CRC) is one of the most tough-to-detect malignancies and the currently existing treatments are often inefficient to improve the patient’s quality of life [1,2]

  • The loading capacity (LC) trend of the AuNPs on the surface of DNP (AuDNP)-LY@Gelx systems as a function of the estimated gelatin thickness reported in Figure 4c exhibited three different regimes, which can be described with the Boltzmann type equation (Equation (2)): a toe region in which the gelatin thickness did not affect the LC capacity of the system (0–5 nm); a linear region in which the LC was directly proportional to the estimated gelatin thickness (5–11 nm) due to the increase of the interactions between the drug and gelatin molecules; and a saturation region (11–14 nm) in which the drug, whose experimental concentration was kept constant (1 mg · mL−1), represents the limiting factor of the entrapment efficiency in the gelatin matrix

  • NPs can be coated by a polymeric shell that acts as a drug gatekeeper and enhances the carrier loading capacity

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Summary

Introduction

Colorectal cancer (CRC) is one of the most tough-to-detect malignancies and the currently existing treatments are often inefficient to improve the patient’s quality of life [1,2]. The high-dose administration and fast metabolization of Galunisertib can be highly toxic due to the rapid generation of undesired metabolites in the plasma [5] For this therapeutic agent, nanoscale delivery systems can protect the drug from the liver’s primary mechanism of metabolization, improving their therapeutic effect and reducing the administered dose [6]. Our group showed that when Galunisertib is encapsulated in DNPs capped by gelatin, the drug effect on CRC cells is strongly enhanced, allowing to lower the needed administered dose. We demonstrate that the DNP loading capacity can be tuned by varying the amount of gelatin rather than the mass of DNPs and that both the formation and degradation of the shells can be monitored spectroscopically, overcoming the need for high-resolution instrumentation. Through the developed optical modeling we can extract information on different design parameters of optical drug delivery systems, such as the loading capacity, coating thickness, and drug release by monitoring the plasmonic resonance of the system

Results and Discussion
Application of the Model to the Monitoring of the In-Situ LY Drug Release
Materials and Reagents
Apparatus and Characterizations
Numerical Simulations
In Vitro Drug Loading and Release Studies
Conclusions
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