Andrea C. Ortiz

Objectives This review critically examines the integration of nanocarriers into oral tablet formulations, focusing on compaction strategies, excipient selection, and the impact of nanosystem properties on manufacturability, drug release, and biopharmaceutical performance. Literature search A comprehensive literature search was conducted in PubMed and Web of Science to identify peer-reviewed publications reporting oral tablet formulations based on nanocarriers, including polymeric nanoparticles, liposomes, mesoporous silica nanoparticles (MSNs), dendrimers, and hybrid or lipid-based nanosystems. Relevant data on formulation strategies, compression methods, excipients, in vitro and in vivo performance, and critical quality attributes were extracted and analyzed. Results After removing duplicates and assessing relevance, 40 studies were selected for in-depth review. Polymeric nanoparticles consistently enhanced controlled release, with chitosan, polylactide acid, and casein-based systems enabling mucoadhesion or delayed dissolution. Silica-based nanocarriers, particularly MSNs, enhanced powder flow and tablet hardness when used within an optimal concentration range, whereas higher loadings negatively affected compressibility. Lipid nanoparticles and self-emulsifying systems facilitated immediate or sustained release while improving drug solubility. Freeze-drying, spray drying, and 3D printing were pivotal for stabilizing sensitive carriers. Hybrid systems, including metal–organic frameworks and chitosomes, provided tailored release and pharmacokinetic enhancement. Challenges included aggregation, poor flow, mechanical fragility, and regulatory limitations, though advances in excipient engineering, smart coatings, and manufacturing technologies are mitigating these barriers. Conclusions Nanocarrier-based tablets are a promising frontier for improving oral drug delivery, offering controlled release, enhanced bioavailability, and potential for multifunctionality. While nanocrystal-based products dominate the market, newer nanosystems show increasing promise. Future directions include personalized therapies, oral delivery of biologics, and integration of multifunctional nanocarriers enabled by emerging technologies such as 3D printing and stimuli-responsive coatings.

Background: The increasing prevalence of multidrug-resistant bacterial infections highlights the need for drug-delivery strategies that improve antimicrobial exposure and sustain therapeutic activity. In this study, ciprofloxacin-loaded nanostructured lipid carriers (NLC-CIP) were developed and evaluated to better understand how formulation-dependent release behavior influences antibacterial performance against Escherichia coli. Methods: NLC-CIP were prepared and characterized in terms of size, polydispersity, encapsulation efficiency, and colloidal stability. In vitro release profiles were evaluated across different pH conditions, followed by kinetic modeling. Stability under refrigerated storage was assessed. Antibacterial performance was determined through IC₅₀ measurements and dynamic growth-kinetic analyses, while cytotoxicity was evaluated in HepG2 cells. Results: Ciprofloxacin incorporation increased hydrodynamic diameter (~116 to 194 nm) while preserving low polydispersity (PdI~0.04), high colloidal stability, and encapsulation efficiency (96%). Release studies showed medium-dependent behavior, with rapid release at pH 1.2, 4.5, and 7.4, and more sustained profile at pH 6.8, consistent with diffusion-controlled kinetics (Weibull model). Refrigerated storage preserved release profiles while slowing early-stage kinetics. NLC-CIP showed improved apparent antibacterial activity, reducing the IC₅₀ from 4.9 to 1.2 ng/mL, and sustained bacterial suppression by decreasing growth rates and prolonging doubling times. Unloaded NLCs showed no antibacterial activity, and cytotoxicity assays confirmed favorable biocompatibility. Conclusions: Overall, these results show that NLC-based encapsulation can modulate ciprofloxacin release and reshape drug exposure over time, thereby improving antibacterial performance under the tested conditions. This study supports integrated release and growth-kinetic analyses as a more informative framework for evaluating lipid-based antibiotic delivery systems.

Propolis is a chemically complex natural product with recognized antioxidant potential, but its compositional heterogeneity and poor aqueous solubility complicate formulation and interpretation of in vitro release behavior. In this study, a nanostructured lipid carrier (NLC) based on Gelucire^® 44/14 was developed as a physicochemical platform to modulate the accessibility of a selected Chilean ethanolic propolis extract. Propolis extracts from different origins were first screened using complementary antioxidant assays (DPPH, ABTS, ORAC, FRAP), leading to the selection of the Peñaflor extract, which exhibited the highest phenolic content (~41 mg GAE/g) and antioxidant capacity. The selected extract was incorporated into NLCs with encapsulation efficiencies above 90%, a narrow size distribution (~200 nm), and high stability over 90 days. Under simple aqueous conditions, propolis release remained limited (<15% over 6 h), consistent with diffusion- and partition-controlled transport. In simulated gastrointestinal media containing bile components, pronounced pH- and composition-dependent effects were observed. While fed-state intestinal conditions induced extensive morphological remodeling without increasing the analytically accessible fraction (<3% at 4 h), fasted-state intestinal media promoted a higher accessible fraction (~14% within 1 h) without complete carrier disruption, as confirmed by transmission electron microscopy. Preliminary cytocompatibility studies in HepG2 cells showed acceptable viability at 10–40 µg/mL and concentration-dependent effects at higher doses. Overall, this work demonstrates that bile components modulate propolis accessibility through dynamic partitioning and colloidal reorganization rather than simple carrier breakdown, providing a physicochemical framework for future digestion and absorption studies.

Antioxidant nanomaterials, particularly mesoporous silica nanoparticles (MSNs) functionalized with polyphenols, offer innovative solutions for protecting oxidation-sensitive components and enhancing bioavailability in pharmaceuticals or extending the shelf life of nutraceutical and food products. This study investigates the influence of MSNs functionalized with caffeic acid (MSN-CAF) on powder flow properties and their tableting performance. Aminated MSNs were synthesized via co-condensation and conjugated with caffeic acid using EDC/NHS chemistry. Antioxidant capacity was evaluated using DPPH^●, ABTS^●+, ORAC, and FRAP assays. Powder blends with varying MSN-CAF concentrations (10–70%) were characterized for flow properties (angle of repose, Hausner ratio, Carr’s index), tablets were produced via direct compression, and critical quality attributes (weight uniformity, hardness, friability, disintegration, nanoparticle release) were assessed. MSN-CAF exhibited reduced antioxidant capacity compared with free caffeic acid due to pore entrapment but retained significant activity. Formulation F1 (10% MSN-CAF) showed excellent flowability (angle of repose: 12°, Hausner ratio: 1.16, Carr’s index: 14%), enabling robust tablet production with rapid disintegration, low friability, and complete nanoparticle release in 10 min. Additionally, the antioxidant nanomaterial demonstrated biocompatibility with the HepG2 cell line. MSN-CAF is a versatile nanoexcipient for direct compression tablets, offering potential as an active packaging agent and delivery system in the nutraceutical and food industries.

Background/Objectives: Rifampicin is a typical antibiotic used for the treatment of Staphylococcus aureus (S. aureus) infections; however, its clinical utility is limited by poor aqueous solubility, chemical instability, and increasing bacterial resistance. Nanostructured lipid carriers (NLCs) offer a promising strategy to improve drug solubility, stability, and antimicrobial performance. Methods: In this study, rifampicin-loaded NLC (NLC-RIF) was developed using a hot homogenization with a low energy method and characterized in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, colloidal stability, and drug loading. Results: In vitro release studies under sink conditions demonstrated a biphasic release pattern, best described by the Korsmeyer–Peppas model, suggesting a combination of diffusion and matrix erosion mechanisms. Antimicrobial activity against S. aureus revealed a substantial increase in potency for NLC-RIF, with an IC₅₀ of 0.46 ng/mL, approximately threefold lower than that of free rifampicin. Cytotoxicity assays in HepG2 cells confirmed over 90% cell viability across all tested concentrations. Conclusions: These findings highlight the potential of NLC-RIF as a biocompatible and effective nanocarrier system for enhancing rifampicin delivery and antibacterial activity.

Background/Objectives: The absence of standardized protocols for assessing in vitro drug release from nanocarriers poses significant challenges in nanoformulation development. This study evaluated three in vitro methods: sample and separate without medium replacement (independent batch), sample and separate with medium replacement, and a dialysis bag method, to characterize the release of rhodamine B from mesoporous silica nanoparticles (MSNs). Methods: Each method was examined under varying agitation conditions (shaking versus stirring). MSNs were synthesized via the sol-gel method, exhibiting a hydrodynamic diameter of 202 nm, a zeta potential of −23.5 mV, and a surface area of 688 m²/g, with a drug loading efficiency of 32.4%. Results: Release profiles revealed that the independent batch method exhibited a rapid initial burst followed by a plateau after 4 h, attributed to surface saturation effects. Conversely, the sample and separate with medium replacement method sustained the release up to 60% over 48 h, maintaining sink conditions. The dialysis method showed agitation-dependent variability, with magnetic stirring using a longer stir bar enhancing release. Kinetic analyses indicated first-order kinetics with non-Fickian diffusion. Conclusions: Overall, the results indicate that both the selection of the in vitro method and the agitation technique play a crucial role in determining the apparent drug release kinetics from nanocarriers. These findings highlight the critical role of experimental design in interpreting nanocarrier release kinetics, advocating for tailored protocols to improve reproducibility and in vitro–in vivo correlations in nanoformulation.

Stimuli-responsive nanomaterials have emerged as a promising strategy for inclusion in anticancer therapy. In particular, pH-responsive silica nanocarriers have been studied to provide controlled drug delivery in acidic tumor microenvironments. However, the intracellular microenvironment that the nanosystem must face has an impact on the anticancer effect; therefore, the design of the nanocarrier and the mechanisms that govern drug release play a crucial role in optimizing efficacy. Here, we synthesized and characterized mesoporous silica nanoparticles with transferrin conjugated on their surface via a pH-sensitive imine bond (MSN-Tf) to assess camptothecin (CPT) loading and release. The results showed that CPT-loaded MSN-Tf (MSN-Tf@CPT) had a size of ca. 90 nm, a zeta potential of −18.9 mV, and a loaded content of 13.4%. The release kinetic data best fit a first-order model, and the predominant mechanism was Fickian diffusion. Additionally, a three-parameter model demonstrated the drug-matrix interaction and impact of transferrin in controlling the release of CPT from the nanocarrier. Taken together, these results provide new insights into the behavior of a hydrophobic drug released from a pH-sensitive nanosystem.

Lipid nanocarriers have a great potential for improving the physicochemical characteristics and behavior of poorly water-soluble drugs, such as aqueous dispersibility and oral bioavailability. This investigation presents a novel nanostructured lipid carrier (NLC) based on a mixture of solid lipid glycerides, fatty acid esters of PEG 1500 (Gelucire^® 44/14), and an oil mix composed of capric and caprylic triglycerides (Miglyol^® 812). These NLCs were developed by a simple low-energy method based on melt emulsification to yield highly encapsulating and narrowly distributed nanoparticles (~100 nm, PdI = 0.1, and zeta potential = ~−10 mV). Rhodamine 123 was selected as a poorly water-soluble drug model and owing to its spectroscopic properties. The novel NLCs were characterized by dynamic light scattering (DLS), zeta potential, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and colloidal stability. The drug release was determined through a dialysis bag and vertical Franzs’ cells to provide insights about the methods’ suitability, revealing similar performance regardless of their different fluid dynamics. Rhodamine 123 followed a characteristic biphasic release profile owing to the swelling of the hydrophilic polymer coating and diffusion process from the lipid core as revealed by the Korsmeyers–Peppas kinetic modeling. Moreover, to elucidate the formation and incorporation of Rhodamine 123 into the NLC core, several molecular dynamics simulations were conducted. The temperature was shown to be an important condition to improve the formation of the nanoparticles. In addition, the liquid lipid incorporation to the formulation forms nanoparticles with imperfect centers, in contrast to nanoparticles without it. Moreover, Miglyol^® 812 improves hydrophobic molecule solubility. These results suggest the potential of novel NLC as a drug delivery system for poorly water-soluble drugs.