Release Kinetics Research Articles

Repurposing simvastatin in cancer treatment: an updated review on pharmacological and nanotechnological aspects.

Management of cancer is challenging due to non-targeting and high side effect issues. Drug repurposing is an innovative method for employing medications for other disease therapy in addition to their original use. Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor, is a lipid-lowering drug that is being studied for the treatment of cancer in various in vitro and in vivo models. Nanotechnology offers a potential platform for incorporation of drugs with enhanced pharmaceutical (solubility, release characteristics, stability, etc.) and biological characteristics (targeting, pharmacokinetic, pharmacodynamic). Utilizing a variety of resources such as Scopus, Springer, Web of Science, Elsevier, Bentham Science, Taylor & Francis, and PubMed, a thorough literature search was carried out by looking through electronic records published between 2003 and 2024. The keywords used were simvastatin, drug repurposing, anti-cancer simvastatin, pharmaceutical properties of simvastatin, simvastatin nanoformulations, simvastatin patents, clinical trials, etc. Numerous articles were looked for, filtered, checked out, and incorporated. Pure simvastatin has been researched as a repurposed medication for the treatment of cancer in several in vitro and in vivo models, such as carcinoma of the lung, colon, liver, prostate, breast, and skin. Simvastatin also incorporated into different nanocarriers (nanosuspensions, microparticles/nanoparticles, liposomes, and nanostructured lipid carriers) and showed improvement in solubility, bioavailability, drug loading, release kinetics, and targeting. Clinical trial and patent reports suggest potential of simvastatin in cancer therapy. The preclinical studies of pure simvastatin in in vitro and in vivo models showed the potential for its ability to inhibit cancer cell growth and further incorporation into nanoformulations strengthened its preclinical and pharmaceutical characteristics.

Modulating Adjuvant Release Kinetics from Scaffold Vaccines to Tune Adaptive Immune Responses.

Increasing the potency, quality and durability of vaccines represents a major public health challenge. A critical parameter that shapes vaccine immunity is the spatiotemporal context in which immune cells interact with antigen and adjuvant. While various material-based strategies have demonstrated that extended antigen release enhances both cellular and humoral immunity, the effect of adjuvant kinetics on vaccine-mediated immunity remains incompletely understood. Here, we use a previously characterized mesoporous silica rod (MPS) biomaterial vaccine to develop a facile, electrostatics-driven approach to tune in vivo kinetics of the TLR9 agonist CpG. We demonstrate that rapid release of CpG from MPS vaccines, mediated by alterations in MPS chemistry that tune surface charge, generates potent cytotoxic T cell responses and robust, Th1-skewed IgG2a/c antibody titers. Immunophenotyping of lymphoid organs after MPS vaccination with slow or fast CpG release kinetics suggests that differential engagement of migratory dendritic cells and natural killer cells may contribute to the more potent responses observed with rapid adjuvant release. Taken together, these findings suggest that vaccine approaches that pair sustained release of antigen with rapid release of adjuvants with similar characteristics to CpG may drive particularly potent Th1 responses. This article is protected by copyright. All rights reserved.

HER2 siRNA Facilitated Gene Silencing Coupled with Doxorubicin Delivery: A Dual Responsive Nanoplatform Abrogates Breast Cancer.

The present study investigated the concurrent delivery of antineoplastic drug, doxorubicin, and HER2 siRNA through a targeted theranostic metallic gold nanoparticle designed using polysaccharide, PSP001. The as-synthesized HsiRNA@PGD NPs were characterized in terms of structural, functional, physicochemical, and biological properties. HsiRNA@PGD NPs exposed adequate hydrodynamic size, considerable ζ potential, and excellent drug/siRNA loading and encapsulation efficiency. Meticulous exploration of the biocompatible dual-targeted nanoconjugate exhibited an appealing biocompatibility and pH-sensitive cargo release kinetics, indicating its safety for use in clinics. HsiRNA@PGD NPs deciphered competent cancer cell internalization, enhanced cytotoxicity mediated via the induction of apoptosis, and excellent downregulation of the overexpressing target HER2 gene. Further in vivo explorations in the SKBR3 xenograft breast tumor model revealed the appealing tumor reduction properties, selective accumulation in the tumor site followed by significant suppression of the HER2 gene which contributed to the exclusive abrogation of breast tumor mass by the HsiRNA@PGD NPs. Compared to free drugs or the monotherapy constructs, the dual delivery approach produced a synergistic suppression of breast tumors both in vitro and in vivo. Hence the drawings from these findings implicate that the as-synthesized HsiRNA@PGD NPs could offer a promising platform for chemo-RNAi combinational breast cancer therapy.

Pluronic P123/DMSO Lyotropic Liquid Crystal for Incorporating Bioactive Substances for Topical Application.

Lyotropic liquid crystals (LLCs) have attracted considerably growing interest in drug delivery applications over the last years. The structure of LLC matrices is complementary to cell membranes and provides an efficient, controlled, and selective release of drugs. In this work, a complex of experimental methods was used to characterize binary LLCs Pluronic P123/DMSO and triple LLC systems Pluronic P123/DMSO/Ibuprofen, which are interesting as transdermal drug delivery systems. Liquid crystalline, thermal, and rheological properties of LLCs were studied. Concentration and temperature areas of the lyomesophase existence were found, and phase transition enthalpies were evaluated. Intermolecular interactions among the components were studied by infrared (IR) spectroscopy. In vitro studies of Ibuprofen (Ibu) release from various LLCs allow differentiation of its release depending on the polymer content. Atomic force microscopy and contact angle methods were used to characterize the surface morphology of the hydrophobic membrane, which was used as a stratum corneum model, and also evaluate the adhesion work of the LLCs. A complex analysis of the results provided by these experimental methods allowed revealing correlations between the phase behavior and rheological characteristics of the LLCs and release kinetics of ibuprofen. The proposed biocompatible systems have considerable potential for a transdermal delivery of bioactive substances.

Design and Development of a Polymeric-Based Curcumin Nanoparticle for Drug Delivery Enhancement and Potential Incorporation into Nerve Conduits

Peripheral nerve injuries (PNI) impact millions of individuals in the United States, prompting thousands of nerve repair procedures annually. Nerve conduits (NC) are commonly utilized to treat nerve injuries under 3 cm but larger gaps still pose a challenge for successful peripheral nerve regeneration (PNR) and functional recovery. This is partly attributed to the absence of bioactive agents such as stem cells or growth factors in FDA-approved conduits due to safety, harvesting, and reproducibility concerns. Therefore, curcumin, a bioactive phytochemical, has emerged as a promising alternative bioactive agent due to its ability to enhance PNR and overcome said challenges. However, its hydrophobicity and rapid degradation in aqueous solutions are considerable limitations. In this work, a nanoscale delivery platform with tannic acid (TA) and polyvinylpyrrolidone (PVP) was developed to encapsulate curcumin for increased colloidal and chemical stability. The curcumin nanoparticles (CurNPs) demonstrate significantly improved stability in water, reduced degradation rates, and controlled release kinetics when compared to free curcumin. Further, cell studies show that the CurNP is biocompatible when introduced to neuronal cells (SH-SY5Y), rat Schwann cells (RSC-S16), and murine macrophages (J774 A.1) at 5 μM, 5 μM, and 10 μM of curcumin, respectively. As a result of these improved physicochemical properties, confocal fluorescence microscopy revealed superior delivery of curcumin into these cells when in the form of CurNPs compared to its free form. A hydrogen peroxide-based oxidative stress study also demonstrated the CurNP’s potential to protect J774 A.1 cells against excessive oxidative stress. Overall, this study provides evidence for the suitability of CurNPs to be used as a bioactive agent in NC applications.

Preparation and Characterization of Amoxicillin-Loaded Polyvinyl Alcohol/Sodium Alginate Nanofibrous Mat: Drug Release Properties, Antibacterial Activity, and Cytotoxicity

AbstractThis study aimed to prepare a polyvinyl alcohol/sodium alginate (PVSA) nanofibrous mat as an amoxicillin (AMOX) delivery system. AMOX was loaded to the PVSA nanofibers during electrospinning, and the AMOX-loaded PVSA (PVSA/AMOX) nanofibrous mat was cross-linked by glutaraldehyde (GA). The PVSA/AMOX nanofibrous mat was characterized by Fourier Transform infrared spectroscopy, scanning electron microscopy, Brunauer–Emmett–Teller, and mercury porosimetry analyses. The thickness, air permeability, and water vapor transmission rate of the PVSA/AMOX nanofibrous mat were 0.43 ± 0.08 mm, 17.2 ± 4.91 L/m2/s, and 1485 ± 13.6 g/m2/d, respectively, which were suitable for wound dressing applications. The tensile strength was 6.73 ± 0.48 MPa and elongation at a maximum load was 81.9 ± 17.0%, within the ranges of human skin’s values. The total porosity was 59.4%, enabling cell adhesion, migration, and proliferation. The PVSA/AMOX nanofibrous mat has high swelling (319 ± 4.2%) and low degradation (2.2 ± 0.1% in 10 days) ratios. The nanofibrous mat cross-linked with 0.25% GA solution for 20 min had a 73.07% cumulative release for 90 min. The drug release kinetics were obeyed to the Korsmeyer-Peppas model. The nanofibrous mat presented antibacterial activity on S. aureus ATCC 29213 and E. coli ATCC 25922, and there was no cytotoxic effect on the human normal keratinocyte cells, demonstrating the potential for use in wound dressing applications.

Encapsulation of W/O/W Acerola Emulsion by Spray Drying: Optimization, Release Kinetics, and Storage Stability

Acerola (Malpighia emarginata DC.) is a sub-tropical and tropical fruit renowned for its high levels of vitamin C and phenolic compounds, which offer health benefits. This study aimed to optimize the spray drying process by determining the inlet and outlet temperatures using response surface methodology (RSM) with the central composite design. Additionally, it aimed to evaluate the release kinetics in the hydrophilic food simulation environment and the stability of the resulting powder under various storage temperatures. The RSM method determined the optimal inlet and outlet temperatures as 157 °C and 91 °C, respectively. High-accuracy prediction equations (R2 ≥ 0.88) were developed for moisture content (3.02%), process yield (91.15%), and the encapsulation yield of total polyphenol content (61.44%), total flavonoid content (37.42%), and vitamin C (27.19%), with a predicted monolayer moisture content below 4.01%, according to the BET equation. The powder exhibited good dissolution characteristics in the acidic hydrophilic food simulation environment and showed greater stability when stored at 10 °C for 30 days, compared to storage at 35 °C and 45 °C.

New Hydrophilic Matrix Tablets for the Controlled Released of Chlorzoxazone

The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20–40 w/w % Kollidon®SR, 3–7 w/w % chitosan while the auxiliary substances: Aerosil® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0–2 h) and the second (2–36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1—the similarity factor, and f2—the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.

Precisely Programmable Degradation and Drug Release Profiles in Triblock Copolyether Hydrogels with Cleavable Acetal Pendants.

Hydrogels hold significant promise as drug delivery systems due to their distinct advantage of sustained localized drug release. However, the challenge of regulating the initial burst release while achieving precise control over degradation and drug-release kinetics persists. Herein, we present an ABA-type triblock copolymer-based hydrogel system with precisely programmable degradation and release kinetics. The resulting hydrogels were designed with a hydrophilic poly(ethylene oxide) midblock and a hydrophobic end-block composed of polyethers with varying ratios of ethoxyethyl glycidyl ether and tetrahydropyranyl glycidyl ether acetal pendant possessing different hydrolysis kinetics. This unique side-chain strategy enabled us to achieve a broad spectrum of precise degradation and drug-release profiles under mildly acidic conditions while maintaining the cross-linking density and viscoelastic modulus, which is unlike the conventional polyester-based backbone degradation system. Furthermore, programmable degradation of the hydrogels and release of active therapeutic agent paclitaxel loaded therein are demonstrated in an in vivo mouse model by suppressing tumor recurrence following surgical resection. Tuning of the fraction of two acetal pendants in the end-block provided delicate tailoring of hydrogel degradation and the drug release capability to achieve the desired therapeutic efficacy. This study not only affords a facile means to design hydrogels with precisely programmable degradation and release profiles but also highlights the critical importance of aligning the drug release profile with the target disease.

Shape Matters: Impact of Mesoporous Silica Nanoparticle Morphology on Anti-Tumor Efficacy

A nanoparticle’s shape is a critical determinant of its biological interactions and therapeutic effectiveness. This study investigates the influence of shape on the performance of mesoporous silica nanoparticles (MSNs) in anticancer therapy. MSNs with spherical, rod-like, and hexagonal-plate-like shapes were synthesized, with particle sizes of around 240 nm, and their other surface properties were characterized. The drug loading capacities of the three shapes were controlled to be 47.46%, 49.41%, and 46.65%, respectively. The effects of shape on the release behaviors, cellular uptake mechanisms, and pharmacological behaviors of MSNs were systematically investigated. Through a series of in vitro studies using 4T1 cells and in vivo evaluations in 4T1 tumor-bearing mice, the release kinetics, cellular behaviors, pharmacological effects, circulation profiles, and therapeutic efficacy of MSNs were comprehensively assessed. Notably, hexagonal-plate-shaped MSNs loaded with PTX exhibited a prolonged circulation time (t1/2 = 13.59 ± 0.96 h), which was approximately 1.3 times that of spherical MSNs (t1/2 = 10.16 ± 0.38 h) and 1.5 times that of rod-shaped MSNs (t1/2 = 8.76 ± 1.37 h). This research underscores the significance of nanoparticles’ shapes in dictating their biological interactions and therapeutic outcomes, providing valuable insights for the rational design of targeted drug delivery systems in cancer therapy.

Synthesis and drug release kinetics of ciprofloxacin from polyacrylamide/dextran/carbon quantum dots (PAM/Dex/CQD) hydrogels

Sustainable release of drug by utilizing β-cyclodextrin (β-CD) based inclusion complex (IC) is the prime objective of the present work. Herein, polyacrylamide/dextran containing carbon quantum dots (PAM/Dex/CQD) nanocomposite hydrogels are prepared by in situ polymerization of acrylamide. The incorporation of CQD triggers the change in orientation of the PAM/Dex polymeric chains to result the formation of stacked surface morphology of the hydrogel. The average particle size of CQD is found to be 4.13 nm from HRTEM analysis. As-synthesized nanocomposite hydrogel exhibits an optimum swelling ratio of 863 % in aqueous medium. The cytotoxicity study is conducted on HeLa cells by taking up to 2 μM concentration of the prepared nanocomposite hydrogel demonstrate 78 % cell viability. In present study, ciprofloxacin (Cipro) is taken as model drug that achieves release of 64.15 % in 32 h from β-Cipro@PAM/Dex/CQD hydrogels in acidic medium. From theoretical study, release rate constants, R2, Akaike information criterion (AIC) and model selection criterion (MSC) are computed to determine the best fitted kinetics model. Peppas-Sahlin model is the best fitted kinetics model for β-Cipro@PAM/Dex/CQD and concluded that the release of Cipro follows Fickian drug diffusion mechanism in acidic medium.

A comparative study between nanostructured lipid carriers and invasomes for the topical delivery of luteolin: Design, optimization and pre-clinical investigations for psoriasis treatment

Psoriasis is an inflammatory skin condition manifested by hyper-proliferation and reactive aberrant epidermal differentiation, in which genetic and environmental factors have a significant role. The current context is focused on designing novel nanovesicular systems (invasomes) incorporating terpenes with reported anti-inflammatory potential and loaded with a nutraceutical compound (luteolin/Lut) for treatment of psoriasis. Additionally, their topical efficacy in psoriasis treatment compared to lipid-based nanocarriers (nanostructured lipid carriers) was investigated. Invasomes were assessed regarding their particle size (PS), zeta potential (ζ-potential), drug entrapment (EE%), storage stability, in-vitro drug release profile and release kinetics. The optimized vesicles were investigated for their ex-vivo skin deposition and in-vitro anti-inflammatory potential in comparison with nanostructured lipid carriers (NLCs). The optimized formulation was selected to carry out the in-vivo study using rat model of imiquimod-induced psoriasis. Luteolin-invasomes were found to have spherical shape and promising colloidal properties. They possessed PS ranging from 277.80 to 812.91 nm, negative ζ-potential (−35.22–38.55 mV), and high EE% values, which ranged from 89.38 to 99.75 %. Furthermore, they exhibited good stability properties and significant sustainment of drug release in comparison to NLCs. In addition, they were able to enhance Lut deposition by 2.1-fold in the stratum corneum (SC) and 5.5-fold in epidermis and dermis compared to control suspension of Lut. Moreover, invasomes showed more potential to retain Lut into deep skin layers 1.5-fold higher than NLCs. They also displayed higher in-vitro anti-inflammatory activity compared to plain invasomes and control suspension, and comparable activity compared to NLCs. In the in-vivo animal study, the ability of Lut to alleviate psoriatic symptoms was significantly enhanced after its encapsulation in invasomal dispersions, where Lut-invasomes possessed a great inhibitory potential compared to the control Lut suspension, and even to Lut-NLCs. This suggests their efficiency in treating psoriasis, delineating them promising for further use in treating other inflammatory skin conditions.

IBUPROFEN INJECTABLE MICROEMULSION PREPARATION COATED BY CHITOSAN: FORMULATION, CHARACTERIZATION, IN VITRO PERFORMANCE, ANTI-INFLAMMATION ACTIVITY, AND HEMATOLOGY ASSESSMENT

Objective: This study aimed to develop, characterize, and conduct stability evaluations to ensure compliance with intravenous administration for microemulsion ibuprofen injection. In addition, hematology assessment and profile of drug release kinetics were analyzed. Methods: The formulation process commenced by introducing various chitosan concentrations into microemulsion ibuprofen injection, following a method established in a previous study. Formulation parameters studied include particle size, polydispersity index (PDI), zeta potential, kinetic of drug release, anti-inflammation activity using the 1% carrageenin induction method, and hematology assessment. Results: The results showed that the addition of 1% chitosan solution allowed for the development of the ideal microemulsion formula, with droplet size, zeta potential, and PDI of 19.37±0.32 nm,-1.53±0.12 mV, and 0.38±0.02, respectively. Kinetics of chitosan-coated ibuprofen microemulsion (MK) were governed by the squared root of time paradigm, suggesting that drug release proceeded by diffusion and was influenced by the carrier. Compared to the other groups, the paw injected with MK indicated a strong anti-inflammatory effect and did not differ significantly from the control group (p>0.05). However, Hematology analysis showed no statistically significant variations in leukocyte and erythrocyte profiles between the treatment and control groups (p>0.05). Conclusion: MK met the criteria as an intravenous preparation based on the characteristics and safety.

Nanofiber-based Delivery of Luliconazole: Fabrication, Characterization, and Therapeutic Performance Assessment.

This study introduces and assesses the potential of a Luliconazole-loaded nanofiber (LUL-NF) patch, fabricated through electrospinning, for enhancing topical drug delivery. The primary objectives involve evaluating the nanofiber structure, characterizing physical properties, determining drug loading and release kinetics, assessing antifungal efficacy, and establishing the long-term stability of the NF patch. LUL-NF patches were fabricated via electrospinning and observed by SEM at approximately 200nm dimensions. The comprehensive analysis included physical properties (thickness, folding endurance, swelling ratio, weight, moisture content, and drug loading) and UV analysis for drug quantification. In vitro studies explored sustained drug release kinetics, while microbiological assays evaluated antifungal efficacy against Candida albicans and Aspergillus Niger. Stability studies confirmed long-term viability. Comparative analysis with the pure drug, placebo NF patch, LUL-NF patch, and Lulifod gel was conducted using agar diffusion, revealing enhanced performance of the LUL-NF patch. SEM analysis revealed well-defined LUL-NF patches (0.80mm thickness) with exceptional folding endurance (> 200 folds) and a favorable swelling ratio (12.66 ± 0.73%). The patches exhibited low moisture uptake (3.4 ± 0.09%) and a moisture content of 11.78 ± 0.54%. Drug loading in 1 cm2 section was 1.904 ± 0.086mg, showing uniform distribution and sustained release kinetics in vitro. The LUL-NF patch demonstrated potent antifungal activity. Stability studies affirmed long-term stability, and comparative analysis highlighted increased inhibition compared to a pure drug, LUL-NF patch, and a commercial gel. The electrospun LUL-NF patch enhances topical drug delivery, promising extended therapy through single-release, one-time application, and innovative drug delivery strategies, supported by thorough analysis.

Bioactive Glasses Modulate Anticancer Activity and Other Polyphenol-Related Properties of Polyphenol-Loaded PCL/Bioactive Glass Composites.

In this work, bioactive glass (BG) particles obtained by three different methods (melt-quenching, sol-gel, and sol-gel-EISA) were used as modifiers of polyphenol-loaded PCL-based composites. The composites were loaded with polyphenolic compounds (PPh) extracted from sage (Salvia officinalis L.). It was hypothesized that BG particles, due to their different textural properties (porosity, surface area) and surface chemistry (content of silanol groups), would act as an agent to control the release of polyphenols from PCL/BG composite films and other significant properties associated with and affected by the presence of PPh. The polyphenols improved the hydrophilicity, apatite-forming ability, and mechanical properties of the composites and provided antioxidant and anticancer activity. As the BG particles had different polyphenol-binding capacities, they modulated the kinetics of polyphenol release from the composites and the aforementioned properties to a great extent. Importantly, the PPh-loaded materials exhibited multifaceted and selective anticancer activity, including ROS-mediated cell cycle arrest and apoptosis of osteosarcoma (OS) cells (Saos-2) via Cdk2-, GADD45G-, and caspase-3/7-dependent pathways. The materials showed a cytotoxic and antiproliferative effect on cancerous osteoblasts but not on normal human osteoblasts. These results suggest that the composites have great potential as biomaterials for treating bone defects, particularly following surgical removal of OS tumors.

Enzyme-responsive mannose-grafted magnetic nanoparticles for breast and liver cancer therapy and tumor-associated macrophage immunomodulation

ABSTRACT Background Chemo-immunotherapy modifies the tumor microenvironment to enhance the immune response and improve chemotherapy. This study introduces a dual-armed chemo-immunotherapy strategy combating breast tumor progression while re-polarizing Tumor-Associated Macrophage (TAM) using prodigiosin-loaded mannan-coated magnetic nanoparticles (PG@M-MNPs). Methods The physicochemical properties of one-step synthetized M-MNPs were analyzed, including X-ray diffraction, FTIR, DLS, VSM, TEM, zeta potential analysis, and drug loading content were carried out. Biocompatibility, cancer specificity, cellular uptake, and distribution of PG@M-MNPs were investigated using fluorescence and confocal laser scanning microscopy, and flow cytometry. Furthermore, the expression levels of IL-6 and ARG-1 after treatment with PG and PG@M-MNPs on M1 and M2 macrophage subsets were studied. Results The M-MNPs were successfully synthesized and characterized, demonstrating a size below 100 nm. The release kinetics of PG from M-MNPs showed sustained and controlled patterns, with enzyme-triggered release. Cytotoxicity assessments revealed an enhanced selectivity of PG@M-MNPs against cancer cells and minimal effects on normal cells. Additionally, immuno-modulatory activity demonstrates the potential of PG@M-MNPs to change the polarization dynamics of macrophages. Conclusion These findings highlight the potential of a targeted approach to breast cancer treatment, offering new avenues for improved therapeutic outcomes and patient survival.

Impact of Nebulization on the Physicochemical Properties of Polymer-Lipid Hybrid Nanoparticles for Pulmonary Drug Delivery.

Nanoparticles (NPs) have shown significant potential for pulmonary administration of therapeutics for the treatment of chronic lung diseases in a localized and sustained manner. Nebulization is a suitable method of NP delivery, particularly in patients whose ability to breathe is impaired due to lung diseases. However, there are limited studies evaluating the physicochemical properties of NPs after they are passed through a nebulizer. High shear stress generated during nebulization could potentially affect the surface properties of NPs, resulting in the loss of encapsulated drugs and alteration in the release kinetics. Herein, we thoroughly examined the physicochemical properties as well as the therapeutic effectiveness of Infasurf lung surfactant (IFS)-coated PLGA NPs previously developed by us after passing through a commercial Aeroneb® vibrating-mesh nebulizer. Nebulization did not alter the size, surface charge, IFS coating and bi-phasic release pattern exhibited by the NPs. However, there was a temporary reduction in the initial release of encapsulated therapeutics in the nebulized compared to non-nebulized NPs. This underscores the importance of evaluating the drug release kinetics of NPs using the inhalation method of choice to ensure suitability for the intended medical application. The cellular uptake studies demonstrated that both nebulized and non-nebulized NPs were less readily taken up by alveolar macrophages compared to lung cancer cells, confirming the IFS coating retention. Overall, nebulization did not significantly compromise the physicochemical properties as well as therapeutic efficacy of the prepared nanotherapeutics.

Influence of Casting Variables on Release Kinetics of Orally Disintegrating Film.

As a new form for supplying vitamin C, orally disintegrating films (ODFs) were developed C based on hyaluronic acid (HA) under varying casting conditions and the properties were analyzed. The films with different thicknesses (2, 3, and 8 mm, for CT2, CT4, and CT8, respectively) were produced by adjustments made to casting height. Two types of 8 mm thick ODFs produced by single or double casting (4 + 4 mm for CTD4+4) methods were also compared. As film thickness increased, water vapor permeability and tensile strength also increased. Even at equal thickness, manufacturing with double casting exhibited a stronger texture and reduced disintegration compared to single casting. All ODFs met the World Health Organization's recommended daily vitamin C intake (45 mg/day) with a single sheet. Films showed over 80% dissolution in various solvents, adhering to the Hixson-Crowell cube root law, indicating vitamin C release occurred via porous penetration of the eluate. For CT2, CT4, and CTD4+4, vitamin C release was primarily governed by diffusion within the gel matrix and HA erosion. However, for CT8, HA erosion-induced release somewhat dominated. Based on the sensory test, it seems desirable to adjust the thickness of the film to 2 or 4 mm, because a thickness greater than that increased the foreign body sensation due to prolonged residence in the oral cavity.

UiO-66(Zr) as drug delivery system for non-steroidal anti-inflammatory drugs

The toxicity for the human body of non-steroidal anti-inflammatory drugs (NSAIDs) overdoses is a consequence of their low water solubility, high doses, and facile accessibility to the population. New drug delivery systems (DDS) are necessary to overcome the bioavailability and toxicity related to NSAIDs. In this context, UiO-66(Zr) metal-organic framework (MOF) shows high porosity, stability, and load capacity, thus being a promising DDS. However, the adsorption and release capability for different NSAIDs is scarcely described. In this work, the biocompatible UiO-66(Zr) MOF was used to study the adsorption and release conditions of ibuprofen, naproxen, and diclofenac using a theoretical and experimental approximation. DFT results showed that the MOF-drug interaction was due to an intermolecular hydrogen bond between protons of the groups in the defect sites, (μ3 − OH, and − OH2) and a lone pair of oxygen carboxyl functional group of the NSAIDs. Also, the experimental results suggest that the solvent where the drug is dissolved affects the adsorption process. The adsorption kinetics are similar between the drugs, but the maximum load capacity differs for each drug. The release kinetics assay showed a solvent dependence kinetics whose maximum liberation capacity is affected by the interaction between the drug and the material. Finally, the biological assays show that none of the systems studied are cytotoxic for HMVEC. Additionally, the wound healing assay suggests that the UiO-66(Zr) material has potential application on the wound healing process. However, further studies should be done.

Pioglitazone Phases and Metabolic Effects in Nanoparticle-Treated Cells Analyzed via Rapid Visualization of FLIM Images.

Fluorescence lifetime imaging microscopy (FLIM) has proven to be a useful method for analyzing various aspects of material science and biology, like the supramolecular organization of (slightly) fluorescent compounds or the metabolic activity in non-labeled cells; in particular, FLIM phasor analysis (phasor-FLIM) has the potential for an intuitive representation of complex fluorescence decays and therefore of the analyzed properties. Here we present and make available tools to fully exploit this potential, in particular by coding via hue, saturation, and intensity the phasor positions and their weights both in the phasor plot and in the microscope image. We apply these tools to analyze FLIM data acquired via two-photon microscopy to visualize: (i) different phases of the drug pioglitazone (PGZ) in solutions and/or crystals, (ii) the position in the phasor plot of non-labelled poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), and (iii) the effect of PGZ or PGZ-containing NPs on the metabolism of insulinoma (INS-1 E) model cells. PGZ is recognized for its efficacy in addressing insulin resistance and hyperglycemia in type 2 diabetes mellitus, and polymeric nanoparticles offer versatile platforms for drug delivery due to their biocompatibility and controlled release kinetics. This study lays the foundation for a better understanding via phasor-FLIM of the organization and effects of drugs, in particular, PGZ, within NPs, aiming at better control of encapsulation and pharmacokinetics, and potentially at novel anti-diabetics theragnostic nanotools.