Controlled Drug Release Applications Research Articles

DNA-Scaffolded Disulfide Redox Network for Programming Drug-Delivery Kinetics.

In response to specific stimuli, dynamic covalent materials enable the generation of new structures by reversibly forming/breaking chemical bonds, thus showing great potential for application in controlled drug release. However, using dynamic covalent chemistry to program drug-delivery kinetics remains challenging. Herein, an in situ polymerization-generated DNA-scaffolded disulfide redox network (DdiSRN) is reported in which nucleic acids are used as a scaffold for dynamic disulfide bonds. The constructed DdiSRN allows selective release of loading cargos inside cancer cells in response to redox stimuli. Moreover, the density of disulfide bonds in network can be tuned by precise control over their position and number on DNA scaffolds. As a result, drug-delivery kinetics can be programmed with a half-life, t1/2 , decreasing from 8.3 to 4.4 h, thus facilitating keeping an adequate drug concentration within the therapeutic window. Both in vitro and in vivo studies confirm that co-delivery of DOX and siRNA in combination with fast drug release inside cells using this DdiSRN enhances the therapeutic effect on multidrug-resistant cancer. This nontrivial therapeutic platform enabling kinetic control provides a good paradigm for precision cancer medicine.

Convolutional neural networks for segmentation of FIB-SEM nanotomography data from porous polymer films for controlled drug release.

Phase-separated polymer films are commonly used as coatings around pharmaceutical oral dosage forms (tablets or pellets) to facilitate controlled drug release. A typical choice is to use ethyl cellulose and hydroxypropyl cellulose (EC/HPC) polymer blends. When an EC/HPC film is in contact with water, the leaching out of the water-soluble HPC phase produces an EC film with a porous network through which the drug is transported. The drug release can be tailored by controlling the structure of this porous network. Imaging and characterization of such EC porous films facilitates understanding of how to control and tailor film formation and ultimately drug release. Combined focused ion beam and scanning electron microscope (FIB-SEM) tomography is a well-established technique for high-resolution imaging, and suitable for this application. However, for segmenting image data, in this case to correctly identify the porous network, FIB-SEM is a challenging technique to work with. In this work, we implement convolutional neural networks for segmentation of FIB-SEM image data. The data are acquired from three EC porous films where the HPC phases have been leached out. The three data sets have varying porosities in a range of interest for controlled drug release applications. We demonstrate very good agreement with manual segmentations. In particular, we demonstrate an improvement in comparison to previous work on the same data sets that utilized a random forest classifier trained on Gaussian scale-space features. Finally, we facilitate further development of FIB-SEM segmentation methods by making the data and software used openaccess.

Biomimetic clotrimazole-loaded PLGA films with enhanced adhesiveness for controlled drug release

Biomimetic adhesive surfaces have a number of potential applications in the pharmaceutical and biomedical fields. Fabrication techniques must be adapted to biocompatible and biodegradable materials required for controlled drug release applications. In this study biomimetic adhesive poly(lactic-co-glycolic acid) (PLGA) films loaded with different concentrations of clotrimazole (CTZ) were prepared without combining other adhesive excipients as a controlled release system for potential local oral drug delivery. The films were fully characterized from morphological point of view, and CTZ-loaded biomimetic films exhibited adequate surface pH values, high drug encapsulation efficiency, and loading content. The adhesion strength of the obtained films was significantly higher compared to a flat film reference under different contact conditions. Thermal analysis indicated a decrease of drug crystallinity upon incorporation into PLGA films. The in vitro release of CTZ from PLGA biomimetic films was tested in simulated saliva, and it exhibited an initial burst release, accompanied by a sustained release phase over 10 days. Finally, the mucoadhesive properties of the obtained films was studied using agar/mucin plate as a representative mucosal substrate, and the results demonstrated superior mucoadhesion potential of CTZ-loaded biomimetic film in comparison to its flat counterpart. Having demonstrated the ability to load CTZ into PLGA biomimetic films with enhanced adhesion capacity, the potential use in local oral drug delivery applications warrants further in vitro and in vivo investigations.

Stimulus-responsive nanomaterials under physical regulation for biomedical applications.

Cancer is a growing threat to human beings. Traditional treatments for malignant tumors usually involve invasive means to healthy human tissues, such as surgical treatment and chemotherapy. In recent years the use of specific stimulus-responsive materials in combination with some non-contact, non-invasive stimuli can lead to better efficacy and has become an important area of research. It promises to develop personalized treatment systems for four types of physical stimuli: light, ultrasound, magnetic field, and temperature. Nanomaterials that are responsive to these stimuli can be used to enhance drug delivery, cancer treatment, and tissue engineering. This paper reviews the principles of the stimuli mentioned above, their effects on materials, and how they work with nanomaterials. For this aim, we focus on specific applications in controlled drug release, cancer therapy, tissue engineering, and virus detection, with particular reference to recent photothermal, photodynamic, sonodynamic, magnetothermal, radiation, and other types of therapies. It is instructive for the future development of stimulus-responsive nanomaterials for these aspects.

Mesoporous silicate/alginate composites as a carrier for amitriptyline hydrochloride and in vitro release

The objective of this research is to prepare mesoporous silica (M41) based nanomaterials and encapsulate in the solid polymeric matrix for controlled drug release application. Amitriptyline (AT) -loaded M41/sodium alginate (AL) composite microparticles were prepared by the ion exchanged gelation techniques. Composite microparticles were characterized by FT-IR spectroscopy; surface area analysis and scanning electron microscopy. Here we propose mesoporous silica (M41) for loading of hydrophilic drug, amitriptyline (AT) and further constructed drug loaded M41 into a pH-responsive alginate microparticles. The resulting drug loaded composites microparticles was characterized by powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR), particle size and zeta potential analyzer. Drug loading was confirmed by the decrease of specific surface area and pore volume in the drug loaded composites as well microparticles. The morphology of drug loaded hybrid nanomaterials and composite micro spherical particles were evaluated by scanning and transmission electron microscopy (SEM and TEM, respectively) measurements. The AT release from microspheres composites was pH dependent, and the release rate was much lesser in gastric pH than that in intestinal pH media. Thus, the biocompatible composite spherical particles hold the substantial potential to be further developed as effective and safe drug-delivery carriers. Drug release kinetics ( in vitro in simulated gastric and intestinal fluids) showed that both of them were affected by the properties of materials. The release profile of AT from composites was best fitted in Higuchi kinetic model while the Korsmeyer–Peppas model suggested a non fickian diffusion release mechanism. Such formulations show potential as an efficient controlled drug delivery system.

Developing poly(Agar-co-Glycerol-co-Thyme Oil) based organo-hydrogels for the controlled drug release applications

In this study, it was aimed to investigate the synthesis, characterization and drug release behaviors of organo-hydrogels containing pH-sensitive Agar (A), Glycerol (G), Thyme Oil (TO). The novel organo-hydrogels containing TO were prepared in an emulsion media by the free-radical polymerization and crosslinking reactions among Agar (A), Glycerol (G), TO, N, N, methylenebisacrylamide (MBA) or glutaraldehyde (GA) reagent. Swelling ability (ethanol, acetone, ethanol/ID water (1:1), acetone/ID water (1:1) and gasoline environments and different pH), Fourier Transform Infrared Spectroscopy (FTIR) analysis and 5-Fluorouracil (5-Flu) drug release of the organo-hydrogels were profoundly determined and some structural parameters for organo-hydrogels such as blood clotting, hemolysis analysis, antioxidant analysis were also evaluated in this study. The FTIR spectra confirmed that the TO was bonded onto the organo-hydrogel structure, and the A, G and TO macromolecular chains interpenetrated through the MBA or GA reagent. When swelling analyzes were examined, it was determined that organo-hydrogels, which added thyme oil to the structure, swelled not only in pure water and tap water but also in organic solvents such as ethanol, acetone, ethanol/ID water (1:1), acetone/ID water (1:1) and gasoline. All of the organo-hydrogels synthesized in the light of blood clotting, hemolysis analysis, antioxidant analysis were hemocompatible and could be used within the body. The release results indicated that the organo-hydrogel p(AG-m-TO)3 and p(AG-g-TO)3 had the highest 84.3% and 73.3% release capacity. In addition, it was reported that the release capacities of organo-hydrogels were inversely proportional to the increased amount of TO. When 5-Flu drug release was examined in terms of kinetic models, it was observed that the release adapted to the Korsmeyer-Peppas (KPKM) model. And it was also determined that organo-hydrogels based on p(AG-m-TO) comply with the non-Fick law and organo-hydrogels based on p(AG-g-TO) comply with the Case II transport. In the light of the results obtained, their easy formability, their appropriate mechanical and physical properties make Organo-hydrogels suitable candidates for drug delivery systems.

Sponge-derived natural bioactive glass microspheres with self-assembled surface channel arrays opening into a hollow core for bone tissue and controlled drug release applications

Porous, bioactive microspheres have always been a dream material to biomedical scientists for bone regeneration and drug delivery applications due to their interconnectivity, unique pore geometry, encapsulation ability and porosity spanning macroscopic, microscopic and nanoscopic length scales. Extensive efforts have been made to produce such materials synthetically at a great cost of money, time and labor. Herein, naturally-assembled multifunctional, open-channeled and hollow bioactive micro silica spheres (diameter 209.4 ± 38.5 µm) were discovered in a marine sponge (Geodia macandrewii), by peeling the outer surface of the sterrasters using hydrogen fluoride. The obtained micro silica spheres exhibited valuable characteristics such as homogeneously distributed pores, a cavity in the center of the sphere, and channels (approx. 3000) opening from each pore into the central cavity. Simulated body fluid analysis demonstrated the bioactivity of the micro silica spheres; whereas, no bioactivity was recorded for the original untreated sterrasters. The non-cytotoxicity and osteogenic ability of the isolated microspheres were confirmed through osteoblast cell culture. Finally, these silica based porous microspheres were tested for controlled drug release capacity. The spheres showed excellent loading and release abilities for an anti-cancer drug, carboplatin, in simulated solutions and in human cancer cell culture, HeLa, through a real time cell analyzer system. The drug loading capacity of the porous beads was determined as 10.59%. Considering the unique biological and physicochemical properties, these novel bioactive silica spheres, which we name as giant macroporous silica (GMS), are promising materials for a range of applications including bone tissue engineering and drug delivery.

Nanoparticles and Colloidal Hydrogels of Chitosan-Caseinate Polyelectrolyte Complexes for Drug-Controlled Release Applications.

Chitosan–caseinate nanoparticles were synthesized by polyelectrolyte complex (PEC) formation. Caseinate is an anionic micellar nanocolloid in aqueous solutions, which association with the polycationic chitosan yielded polyelectrolyte complexes with caseinate cores surrounded by a chitosan corona. The pre-structuration of caseinate micelles facilitates the formation of natural polyelectrolyte nanoparticles with good stability and sizes around 200 nm. Such natural nanoparticles can be loaded with molecules for applications in drug-controlled release. In the nanoparticles processing, parameters such as the chitosan degree of acetylation (DA) and molecular weight, order of addition of the polyelectrolytes chitosan (polycation) and caseinate (polyanion), and added weight ratio of polycation:polyanion were varied, which were shown to influence the structure of the polyelectrolyte association, the nanoparticle size and zeta potential. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) analyses revealed the chemical structure of hydrogel colloidal systems consisting of nanoparticles that contain chitosan and caseinate. Transmission electron microscopy (TEM) allowed further characterization of the spherical morphology of the nanoparticles. Furtherly, insulin was chosen as a model drug to study the application of the nanoparticles as a safe biodegradable nanocarrier system for drug-controlled release. An insulin entrapment efficiency of 75% was achieved in the chitosan-caseinate nanoparticles.

Recent Advances in Micro-Electro-Mechanical Devices for Controlled Drug Release Applications.

In recent years, controlled release of drugs has posed numerous challenges with the aim of optimizing parameters such as the release of the suitable quantity of drugs in the right site at the right time with the least invasiveness and the greatest possible automation. Some of the factors that challenge conventional drug release include long-term treatments, narrow therapeutic windows, complex dosing schedules, combined therapies, individual dosing regimens, and labile active substance administration. In this sense, the emergence of micro-devices that combine mechanical and electrical components, so called micro-electro-mechanical systems (MEMS) can offer solutions to these drawbacks. These devices can be fabricated using biocompatible materials, with great uniformity and reproducibility, similar to integrated circuits. They can be aseptically manufactured and hermetically sealed, while having mobile components that enable physical or analytical functions together with electrical components. In this review we present recent advances in the generation of MEMS drug delivery devices, in which various micro and nanometric structures such as contacts, connections, channels, reservoirs, pumps, valves, needles, and/or membranes can be included in their design and manufacture. Implantable single and multiple reservoir-based and transdermal-based MEMS devices are discussed in terms of fundamental mechanisms, fabrication, performance, and drug release applications.

Multidimensional gradient hydrogel and its application in sustained release

We prepared two types of multidimensional gradient hydrogels by simple electrophoresis using spherical graphite electrode. To explore their application in controlled drug release, rhodamine B (RB) and sodium salicylate (SS) were used as oppositely charged drug models respectively to in situ loading into the hydrogels by electrostatic interaction with the charged components accordingly. In both cases, the model drugs and the charged components of the hydrogels were gradiently distributed with the drug concentration increased from the gel surface to the gel core. For the crosslinking gradient hydrogel prepared at 2 V, the network size near the gel surface is about 3 times that of the gel core, and the release rate is 0.85 times of that of the non-gradient hydrogel. For the polymer chain gradient hydrogel prepared at 2.5 V, the relative content of polymer chain near the core of the gel is 2.5 times that of the gel surface, and the release rate is 0.71 times of the non-gradient hydrogel.

Design of polyester structure in amphiphilic copolymer coated on magnetite nanoparticle: Effect on loading and sustaining release of indomethacin

This works presented the surface modification of magnetite nanoparticles (MNPs) with the copolymers containing hydrophilic mPEG and hydrophobic polyester for use in drug controlled release applications. Polyester moieties in the copolymers were adsorbed on MNPs to form hydrophobic layer for entrapment of a hydrophobic indomethacin model drug, while hydrophilic mPEG provided their good water dispersibity. Three different polyester structures in the copolymer for MNP coating were; 1) saturated, 2) unsaturated and 3) crosslinked polyesters. The copolymer structures were characterized via1H NMR and their coatings were confirmed by FTIR. These water dispersible MNPs contained 53–61% copolymer in the complexes with the size ranging between 8 and 14 nm. The MNPs containing saturated polyester showed higher drug entrapment and loading efficiencies than the other two samples. Interestingly, those containing crosslinked polyester exhibited a potential to sustain the release of the entrapped drug. These complexes might be suitable for use as vehicles for entrapment of hydrophobic drugs with tunable and controllable release rate.

Okra (Hibiscus esculentus) gum based hydrophilic matrices for controlled drug delivery applications: Estimation of percolation threshold

This study aims to explore the potential of gum extracted from okra fruit (Hibiscus esculentus) in developing hydrophilic matrices for controlled drug release applications, including determination of its percolation threshold. Flurbiprofen (poorly soluble), theophylline (sparingly soluble) and metformin (freely soluble) were employed as model drugs and incorporated using direct compression into matrices containing 40% w/w of three drugs with different physicochemical properties. Atomic force microscopy was used to study the surface texture properties of developed matrices; the surfaces of the flurbiprofen-based matrices were comparatively rough most likely as a consequence of its poor compactability. Swelling studies found that the swelling rate increased as the concentration of okra gum was increased. However, for all matrices, an increase in the gum concentration resulted in decreased drug release. The estimated percolation threshold of the okra gum calculated was found in the region of ~25% v/v plus initial porosity. Knowing the percolation threshold will enable formulators to use the minimal amount of polymer for sustain release matrices thus the controlling costs and maximising the sustainable potential of okra. This study will not only assist researchers in developing effective okra gum-based extended-release matrices but also expected to contribute towards its exploration at an industrial scale.

An Environmentally Sensitive Silk Fibroin/Chitosan Hydrogel and Its Drug Release Behaviors.

To fabricate environmentally sensitive hydrogels with better biocompatibility, natural materials such as protein and polysaccharide have been widely used. Environmentally sensitive hydrogels can be used as a drug carrier for sustained drug release due to its stimulus responsive performance. The relationship between the internal structure of hydrogels and their drug delivery behaviors remains indeterminate. In this study, environmentally sensitive hydrogels fabricated by blending silk fibroin/chitosan with different mass ratios were successfully prepared using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (EDC)/N-Hydroxysuccinimide (NHS) cross-linking agent. Scanning-electron microscopy (SEM) images showed the microcosmic surface of the gel had a 3-D network-like and interconnected pore structure. The N2 adsorption–desorption method disclosed the existence of macroporous and mesoporous structures in the internal structure of hydrogels. Data of compression tests showed its good mechanical performance. The swelling performance of hydrogels exhibited stimuli responsiveness at different pH and ion concentration. With the increase of pH and ion concentration, the swelling ratios of hydrogels (silk fibroin (SF)/ chitosan (CS) = 8/2 and 7/3) decreased. Methylene blue (MB) was loaded into the hydrogels to confirm the potential of sustained drug release and pH-responsive behavior. Therefore, due to the porous structure, stable mechanical strength, stimuli responsive swelling performance, and drug release behaviors, the SF/CS composite hydrogels have potential applications in controlled drug release.

Core-Shell Structure Design of Hollow Mesoporous Silica Nanospheres Based on Thermo-Sensitive PNIPAM and pH-Responsive Catechol-Fe3+ Complex.

A kind of core-shell hybrid nanoparticle comprised of a hollow mesoporous silica nanoparticles (HMS) core and a copolymer shell bearing N-(3,4-dihydroxyphenethyl) methacrylamide (DMA) and N-isopropylacrylamide (NIPAM) as responsive moieties was prepared. Moreover, the factors that could impact the surface morphology and hierarchical porous structure were discussed. In the presence of Fe3+, catechol-Fe3+ complexes were formed to achieve pH-responsive polymer shell, combining with thermal-sensitiveness of poly(N-isopropylacrylamide). Doxorubicin (DOX) was applied as a model drug and the behaviors of its loading/release behaviors were investigated to prove the idea. The results exhibited a significant drug loading capacity of 8.6% and embed efficiency of 94.6% under 1 mg ml–1 DOX/PBS solution. In fact, the loading capacity of drug can be easily improved to as high as 28.0% by increasing the DOX concentration. The vitro cytotoxicity assay also indicated that the as-prepared nanoparticles have no significant cytotoxicity on RAW 264.7 cells. The in vitro experiment showed that the cumulative release of DOX was obviously dependent on the temperature and pH values. This pH/temperature-sensitive hollow mesoporous silica nanosphere is expected to have potential applications in controlled drug release.

Preparation of polyvinyl alcohol, chitosan and polyurethane-based pH-sensitive and biodegradable hydrogels for controlled drug release applications

In this study, novel hydrogels containing poly(azomethine-urethane) (PAMU), PVA and CS were prepared for controlled drug delivery application. FT-IR was used to confirm hydrogel structures. Thermal stability and mechanical behavior of the hydrogels were also investigated by using a thermogravimetric analysis (TG-DTA) and mechanical measurements. Swelling degree of the hydrogels were carried out at pH = 3, 7, and 12. Antibacterial properties of the hydrogels were also investigated using disc diffusion method. The obtained results showed that controlled drug release, swelling performance, and mechanical properties of the hydrogels were enhanced by increasing the amount of PAMU in the hydrogel matrix.

Effect of the cross-linking density on the gold core oxidation in hybrid core@shell Au@pNIPAM and Janus Au@p4VP systems

Here we report a detailed study that concerns the oxidation of spherical gold nanoparticles (AuNPs) encapsulated into thermo- and pH-responsive microgels. Initially, two types of hybrid systems structured as 50 nm spherical gold nanoparticles coated with a thermo-responsive (N-Isopropylacrylamide) or a pH-responsive (4-vinylpyridine) microgel are synthesized. Then, a gradual gold elimination is achieved introducing each nanohybrid system into a mixture of cetyltrimethylammonium bromide (CTAB) and gold chloride (HAuCl4), finally obtaining hollow colloidal structures with potential application in controlled drug release. The synthesis of Au@pNIPAM and Au@p4VP systems is performed at different crosslinking densities (5, 10 and 15%), and the decrease in the gold plasmon absorption band with the oxidation time is monitored at the two possible microgel states (swollen and collapsed). Two parameters are determined, the Au core etching rate and the molecule diffusion coefficient (AuCl4/CTAB complex). We also present in our study the incorporation of methyl methacrylate (MMA) as co-monomer during the p4VP polymerization to avoid the “Janus” structure in Au@p4VP partiles. This investigation offers the possibility to fabricate thermo- and pH-responsive hollow microgels that can be used for biomedical applications for controlled drug delivery purposes upon change in temperature or pH.

Oxidation-Responsive Nanoassemblies for Light-Enhanced Gene Therapy.

Microenvironment-responsive supramolecular assemblies have attracted great interest in the biomedical field due to their potential applications in controlled drug release. In this study, oxidation-responsive supramolecular polycationic assemblies named CPAs are prepared for nucleic acid delivery via the host-guest interaction of β-cyclodextrin based polycations and a ferrocene-functionalized zinc tetraaminophthalocyanine core. The reactive oxygen species (ROS) can accelerate the disassembly of CPA/pDNA complexes, which would facilitate the release of pDNA in the complexes and further benefit the subsequent transfection. Such improvement in transfection efficiency is proved in A549 cells with high H2 O2 concentration. Interestingly, the transfection efficiencies mediated by CPAs are also different in the presence or absence of light in various cell lines such as HEK 293 and 4T1. The single oxygen (1 O2 ), produced by photosensitizers in the core of CPAs under light, increases the ROS amount and accelerates the disassembly of CPAs/pDNA complexes. In vitro and in vivo studies further illustrate that suppressor tumor gene p53 delivered by CPAs exhibits great antitumor effects under illumination. This work provides a promising strategy for the design and fabrication of oxidation-responsive nanoassemblies with light-enhanced gene transfection performance.

Effect of coagulation bath parameters on the morphology and absorption behavior of a skin–core filament based on biomedical polyurethane and native silk fibroin microparticles

This study investigates the effect of the constituents and temperature of a coagulation bath on the morphology and water absorption behavior of a skin–core filament, which has potential application in the field of controlled drug release, based on biomedical polyurethane (BPU) and native silk fibroin microparticles (NSFPs). BPU solution and BPU/NSFP blend solution were extruded from the cortex and core channel of a coaxial double injector into a coagulation bath with different constituents and at different temperatures to form filaments. Scanning electron microscopy analysis of the skin–core filament prepared by wet-spinning revealed that the addition of ethanol decreased the exchange speed between the solvent and non-solvent and led to the formation of micropores on the surface. Meanwhile, the interface between the cortex and core became pronounced and the water absorption capability of the filament decreased with increasing ethanol concentration in the coagulation bath. The high temperature of the coagulation bath also improved the exchange speed between the solvent and non-solvent; however, its effect on the morphology of the filament was weak. Thus, a skin–core filament with different morphologies and water absorption behaviors was fabricated by controlling the constituents and temperature of the coagulation bath during the wet-spinning process. This skin–core filament has potential applications in controlled drug release.

Dual Crosslinked Gelatin Methacryloyl Hydrogels for Photolithography and 3D Printing.

Gelatin methacryloyl (GelMA) hydrogels have been used in tissue engineering and regenerative medicine because of their biocompatibility, photopatternability, printability, and tunable mechanical and rheological properties. However, low mechanical strength limits their applications in controlled drug release, non-viral gene therapy, and tissue and disease modeling. In this work, a dual crosslinking method for GelMA is introduced. First, photolithography was used to pattern the gels through the crosslinking of methacrylate incorporated amine groups of GelMA. Second, a microbial transglutaminase (mTGase) solution was introduced in order to enzymatically crosslink the photopatterned gels by initiating a chemical reaction between the glutamine and lysine groups of the GelMA hydrogel. The results showed that dual crosslinking improved the stiffness and rheological properties of the hydrogels without affecting cell viability, when compared to single crosslinking with either ultraviolet (UV) exposure or mTGase treatment. Our results also demonstrate that when treated with mTGase, hydrogels show decreased swelling properties and better preservation of photolithographically patterned shapes. Similar effects were observed when three dimensional (3D) printed and photocrosslinked substrates were treated with mTGase. Such dual crosslinking methods can be used to improve the mechanical properties and pattern fidelity of GelMA gels, as well as dynamic control of the stiffness of tissue engineered constructs.

Loading of Cisplatin into Mesoporous Silica Nanoparticles: Effect of Surface Functionalization.

Cisplatin ( cis-diaminedichloroplatinum(II), CDDP) plays a crucial role in the treatment of various malignant tumors. However, its clinical efficacy and applicability are restricted by issues of toxicity and resistance. Here, for drug delivery purposes, the outer surface of MCM-41 mesoporous silica nanoparticles (MSNs) was functionalized with poly(ethylene glycol) ( Mw = 10 000 g/mol) or low-molecular-weight ( Mw = 1800 g/mol) branched polyethyleneimine (PEI). Given the strong affinity of sulfur for platinum, thiol-functionalized MSNs were synthesized for comparison by co-condensation with (3-mercaptopropyl)triethoxysilane. CDDP loading was performed either by adsorption or impregnation in aqueous media without the use of dimethyl sulfoxide as a solubilizer. CDDP loading capacities obtained by impregnation were higher than those obtained by adsorption and varied from 3.9 to 16.1 wt %, depending on the functional group. Loaded nanomaterials were characterized by scanning electron microscopy, scanning transmission electron microscopy-high-angle annular dark-field, and Raman spectroscopy. Depending on the functional groups, platinum-based species were either dispersed in the nanomaterials as nanocrystals or uniformly distributed as molecular species. The spectral signature of CDDP was strongly modified when platinum species were homogeneously distributed within the nanomaterials. Preliminary drug release studies performed at 37 °C showed that the behavior of CDDP-loaded MSNs strongly depends on the nature of the present functional groups. Among the functionalization routes investigated in this paper, PEI-based functionalization showed the most promising results for further applications in controlled drug release with the absence of burst release and a sustained release over 72 h.