Synchrotron SAXS establishes characteristic repeat spacing as a quantitative structural metric directly governing hydrophilic release kinetics, providing a rational design framework linking mesophase architecture to functional performance across a range of payload structures.
Abstract
Liquid crystalline mesophases exhibit structurally programmable internal architectures that enable co-loading of chemically orthogonal molecules within a single composite material. Realizing the potential of these materials for drug delivery requires a quantitative understanding of how tuning the composition affects internal mesophase architecture and consequently performance metrics such as payload release. Here, Flash NanoPrecipitation with hydrophobic ion pairing is used to prepare nanocarriers containing liquid crystalline mesophases co-encapsulating two compounds from widely different chemical classes: hydrophilic polymyxin B (logP –6) with one of four hydrophobic co-core materials (logP 7-11), achieving >75% encapsulation efficiency and up to 32% and 50% mass loadings for polymyxin and co-core. Synchrotron SAXS is used to quantify characteristic mesophase repeat spacing, which is found to be tunable as a function of composition. A strong correlation between d-spacing and polymyxin release rate is presented. Co-core chemistry and weight fraction jointly govern mesophase architecture, and repeat distance emerges as a structural metric linking these to the hydrophilic payload release kinetics. Mucus diffusivity and antibacterial efficacy are assessed as independent performance metrics, and results corroborate the release behavior. These findings establish a quantitative framework connecting material composition, mesophase architecture, and functional performance that can be applied toward rational co-formulation design. ToC Graphic Text Flash NanoPrecipitation yields liquid crystalline nanocarriers co-encapsulating with high efficiency payloads with widely distinct physicochemical properties. Synchrotron SAXS establishes characteristic repeat spacing as a quantitative structural metric directly governing hydrophilic release kinetics, providing a rational design framework linking mesophase architecture to functional performance across a range of payload structures.
Poor aqueous solubility remains a critical barrier to the development of
orally administered drugs, particularly those in the Biopharmaceutics Classification
System (BCS) Class II and IV. In recent years, Mesoporous Silica Materials (MSMs)
have emerged as promising inorganic carriers for improving solubility and bioavailability.
Their unique structural attributes, including high specific surface area, tunable
pore sizes (2–50 nm), large pore volume, and abundant surface silanol groups, enable
efficient drug adsorption, stabilization in the amorphous form, and prevention of recrystallization.
Various synthesis methods such as sol–gel processing, liquid crystal
templating, and microwave-assisted techniques allow precise control of pore architecture,
while diverse drug-loading approaches (e.g., solvent evaporation, incipient wetness
impregnation, co-milling, melt methods) enhance encapsulation efficiency and
dissolution kinetics. Encapsulation within mesopores promotes spatial confinement
and amorphization of poorly soluble drugs, significantly increasing dissolution rates
and oral bioavailability. Functionalization of Mesoporous Silica Nanoparticles
(MSNs) with hydrophilic groups or targeting ligands further improves wettability,
dispersion, and site-specific delivery. Applications span the delivery of hydrophobic
agents including fenofibrate, itraconazole, and carvedilol, with multiple-fold improvements
in dissolution and therapeutic efficacy. Poor aqueous solubility remains a
major limitation in the oral delivery of BCS class II and IV drugs. Mesoporous Silica
Materials (MSMs) have emerged as versatile inorganic nanocarriers due to their high
surface area, tunable pore architecture, and amenability to surface functionalization,
enabling efficient drug loading, amorphization, and dissolution enhancement. This
review uniquely integrates synthesis strategies, pharmaceutical optimization techniques,
and biological performance under a unified framework, with particular emphasis
on translational relevance. Recent advances in solvent-free loading, surface
engineering, and stimuli-responsive systems are critically discussed alongside emerging
in vivo pharmacokinetic, biodegradation, and toxicological evidence. Despite
promising preclinical outcomes, challenges related to large-scale manufacturing,
long-term biocompatibility, controlled clearance, and regulatory standardization remain.
Addressing these gaps through biodegradable designs, rational particle engineering,
and robust in vivo evaluation will be crucial for advancing mesoporous silica-
based drug delivery systems toward clinical application.
Harshad S. Kapare, Kunal R. Girase, P. Karwa et al.· Current Materials Science· 0 citations
The development of efficient and targeted drug delivery systems remains a significant challenge, particularly for active pharmaceutical ingredients with poor aqueous solubility. Among various nanocarrier systems, Mesoporous Silica Nanoparticles (MSNs) have emerged as promising candidates due to their high surface area, tunable pore size (2-50 nm), thermal stability, and chemical modifiability. This review comprehensively discusses the rationale behind the utilization of MSN as drug delivery systems, focusing on how the type and concentration of surfactants, along with surface functionalization strategies, influence their physicochemical characteristics and pharmacokinetic performance. The synthesis of MSNs typically involves sol-gel processes using silica precursors (e.g., tetraethyl orthosilicate) and surfactants (e.g., cetyl trimethyl ammonium bromide, Pluronic F127), which dictate the morphology, particle size, and pore architecture of the resulting nanoparticles. Furthermore, surface modifications employing functional groups such as polyethylene glycol or pH-responsive polymers enhance biocompatibility, prolong systemic circulation, and enable controlled and site-specific drug release. Evidence from recent studies demonstrates that MSNs significantly improve drug loading efficiency, enhance solubility and bioavailability, and reduce off-target toxicity. Consequently, MSNs represent a highly versatile and modifiable platform with considerable potential for addressing the limitations of conventional drug delivery systems, particularly in oncology and the treatment of chronic diseases.
Ahmad Ainurofiq, Y. Ramadhana, Salma Aqilah Rachmadani et al.· Recent Advances in Drug Deli...· 0 citations
Magnetothermally responsive nanocarriers represent a promising platform for spatio-temporally controlled drug delivery by combining alternating magnetic field (AMF)-induced heating with thermally triggered cargo release. Among the available architectures, magnetite-core/mesoporous-silica-shell (Fe3O4@mSiO2) nanoparticles functionalized with thermoresponsive polymer gatekeepers are particularly attractive. These systems integrate a magnetic heat source, a mesoporous drug reservoir, and temperature-dependent control of pore accessibility. This review examines the fundamental principles of magnetic hyperthermia, including heat-generation mechanisms, specific absorption rate (SAR), intrinsic loss power (ILP), AMF parameters and safety, and the interplay between Néel and Brownian relaxation. It also critically discusses core–shell synthesis and architecture, drug-loading strategies, PNIPAM-, PNVCL-, and other LCST-type gatekeepers, and the physicochemical characterization required to validate the complete nanocarrier. Evidence for combined magnetic hyperthermia and chemotherapy is assessed together with hemocompatibility, immunogenicity, oxidative stress, biodistribution, degradation, long-term retention, and clearance. Although promising magnetothermal release and therapeutic effects have been reported, evidence remains dominated by in vitro studies, with limited in vivo validation. Current clinical experience concerns locally administered iron-oxide hyperthermia rather than complete thermoresponsive Fe3O4@mSiO2 drug-delivery systems. Translation will require standardized magnetothermal and release testing, reproducible scale-up, validated sterilization and endotoxin control, component-resolved pharmacokinetics, and integrated development of the nanocarrier and AMF applicator.
Juliana Jesus, M. Graça, A. S. Pires et al.· Nanomaterials· 0 citations
Polymeric photonic microspheres with visible structural colors offer safe and vibrant alternatives to traditional toxic pigments. These materials are commonly fabricated through confined self-assembly of block copolymers (BCPs) in evaporative emulsions, which can proceed by either microphase separation or organized spontaneous emulsification (OSE) to yield lamellar or porous structures with complementary optical responses. In this study, we show that amphiphilic dendronized brush block copolymers (den-BBCPs) exhibit mechanism-selective self-assembly governed by the volume fraction (f) of hydrophilic segment. At f < 50%, den-BBCPs follow the OSE pathway, generating photonic microspheres with short-range-ordered porous structures and angle-independent structural colors. In contrast, at f > 50%, microphase separation dominates, producing concentric lamellar microspheres with strong specular reflections. This pathway transition arises from the rigid dendronized architecture: increasing the volume fraction of hydrophilic segment amplifies intermolecular repulsions at the highly curved water-in-oil nanodroplet interface, destabilizing interfacial association and redirecting assembly toward microphase separation. This work establishes architectural engineering of den-BBCPs as a powerful strategy for programming self-assembly pathways and creating polymeric photonic pigments with diverse structures and optical properties.
Mohan Zheng, Tong Liang, Zhaoyan Sun et al.· Angewandte Chemie· 0 citations
Translating the solution-phase properties of colloidal nanocrystals into bulk porous monoliths requires gelation strategies that preserve the surface chemistry and electronic structure of the building blocks, a particular challenge for substoichiometric oxides whose function is tied to their oxygen vacancy population. Here, we report the homogeneous gelation of oleylamine-capped, WO3–x nanosheets through a nonredox-active, controlled destabilization route in which interparticle interactions are modulated by tuning the solvation of the ligand shell rather than by oxidative ligand removal. Two orthogonal levers, binary solvent composition and alkylamine chain length, tune the gelation time scale across orders of magnitude, from approximately 1 h to 10 days, while preserving a homogeneous, space-spanning network. Time-resolved synchrotron small-angle X-ray scattering (SAXS) resolves a hierarchical assembly pathway in which one-dimensional (1D) end-to-end attachment of the nanosheets drives network formation, followed by lamellar superstructure development upon solvent removal. Subsequent supercritical CO2 drying yields lightweight, mesoporous WO3–x monoliths that retain the oxygen-deficient character and broadband visible-to-near-infrared absorption of the constituent nanosheets, offering a versatile framework for assembling redox-sensitive oxide nanocrystals into functional porous architectures.
Tzu-Yu Tzeng, Yue-Cih Lin, Jiali Wei et al.· Journal of Physical Chemistr...· 0 citations
Covalent organic frameworks (COFs) are porous, crystalline polymers with broad application prospects. However, their microcrystalline powder morphology severely limits their practical implementation. Herein, a general phase-inversion spherical shaping strategy is reported, enabling the conversion of powdered COFs into robust microspheres with a radially hierarchical pore structure. This method is mild and scalable and has been validated across eight COFs with distinct topologies. The resulting microspheres retain approximately 90% of the intrinsic adsorption capacity of the pristine materials. As a representative demonstration, TAPB-DMTP-COF microspheres were employed in a fixed-bed continuous-flow water treatment system, where 1 g of the material effectively purified over 18 L of real water containing a mixture of bisphenols, with each concentration at 200 ppb, while maintaining high performance over 20 regeneration cycles. More notably, the TAPB-DMTP-COF microspheres themselves possess intrinsic catalytic activity for peroxymonosulfate activation, enabling sequential adsorption enrichment and catalytic degradation within the same fixed-bed column without metal modification. This work establishes a versatile COF shaping platform that extends the application scope of COFs from adsorption to advanced oxidation, offering a viable pathway to overcome a critical bottleneck in their industrial implementation.
Huina Zhou, Ning Zhang, Yingying Li et al.· Angewandte Chemie· 0 citations
