Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases.

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Effects of solid lipid nanocarrier containing methyl urolithin A by coating folate-bound chitosan and evaluation of its anti-cancer activity.

BACKGROUND: Nanotechnology-based drug delivery systems have received much attention over the past decade. In the present study, we synthesized Methyl Urolithin A-loaded solid lipid nanoparticles decorated with the folic acid-linked chitosan layer called MuSCF-NPs and investigated their effects on cancer cells. METHODS: MuSCF-NPs were prepared using a high-pressure homogenization method and characterized using FTIR, FESEM, DLS, and zeta potential methods. Drug encapsulation was assessed by spectrophotometry and its cytotoxic effect on various cancer cells (MDA-MB231, MCF-7, PANC, AGS, and HepG2) by the MTT method. Antioxidant activity was assessed by the ABTS and DPPH methods, followed by expression of genes involved in oxidative stress and apoptosis by qPCR and flow cytometry. RESULTS: The results showed the formation of monodisperse and stable round nanoparticles with a size of 84.8 nm. The drug loading efficiency in MuSCF-NPs was reported to be 88.6%. MuSCF-NPs exhibited selective cytotoxicity against MDA-MB231 cells (IC50 = 40 µg/mL). Molecular analysis showed a significant increase in the expression of Caspases 3, 8, and 9, indicating that apoptosis was occurring in the treated cells. Moreover, flow cytometry results showed that the treated cells were arrested in his SubG1 phase, confirming the pro-apoptotic effect of the nanoparticles. The results indicate a high antioxidant effect of the nanoparticles with IC50 values ​​of 45 µg/mL and 1500 µg/mL against ABTS and DPPH, respectively. The reduction of catalase gene expression confirmed the pro-oxidant effect of nanoparticles in cancer cells treated at concentrations of 20 and 40 µg/mL. CONCLUSIONS: Therefore, our findings suggest that the MuSCF-NPs are suitable candidates, especially for breast cancer preclinical studies.

Levofloxacin loaded chitosan and poly-lactic-co-glycolic acid nano-particles against resistant bacteria: Synthesis, characterization and antibacterial activity.

BACKGROUND: With the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan. METHODS: LVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method. RESULTS: Data revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs. CONCLUSION: These data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.

A Microfluidics-Assisted Double-Barreled Nanobioconjugate Synthesis Introducing Aprotinin as a New Moonlight Nanocarrier Protein: Tested toward Physiologically Relevant 3D-Spheroid Models.

Proteins are promising substances for introducing new drug carriers with efficient blood circulation due to low possibilities of clearance by macrophages. However, such natural biopolymers have highly sophisticated molecular structures, preventing them from being assembled into nanoplatforms with manipulable payload release profiles. Here, we report a novel anticancer nanodrug carrier moonlighting protein, Aprotinin, to be used as a newly identified carrier for cytotoxic drugs. The Aprotinin-Doxorubicin (Apr-Dox) nanobioconjugate was prepared via a single-step microfluidics coflow mixing technique, a feasible and simple way to synthesize a carrier-based drug design with a double-barreled approach that can release and actuate two therapeutic agents simultaneously, i.e., Apr-Dox in 1:11 ratio (the antimetastatic carrier drug aprotinin and the chemotherapeutic drug DOX). With a significant stimuli-sensitive (i.e., pH) drug release ability, this nanobioconjugate achieves superior bioperformances, including high cellular uptake, efficient tumor penetration, and accumulation into the acidic tumor microenvironment, besides inhibiting further tumor growth by halting the urokinase plasminogen activator (uPA) involved in metastasis and tumor progression. Distinctly, in healthy human umbilical vein endothelial (HUVEC) cells, drastically lower cellular uptake of nanobioconjugates has been observed and validated compared to the anticancer agent Dox. Our findings demonstrate an enhanced cellular internalization of nanobioconjugates toward breast cancer, prostate cancer, and lung cancer both in vitro and in physiologically relevant biological 3D-spheroid models. Consequently, the designed nanobioconjugate shows a high potential for targeted drug delivery via a natural and biocompatible moonlighting protein, thus opening a new avenue for proving aprotinin in cancer therapy as both an antimetastatic and a drug-carrying agent.

Eugenol-Loaded Transethosomal Gel for Improved Skin Delivery and Treatment of Atopic Dermatitis.

Atopic dermatitis is a skin condition characterized by lichenification (thickening and increased skin marking), eczematous lesions, dry skin, itching, and pruritus. Eugenol is an aromatic polyphenolic compound that has attracted the attention of researchers due to its anti-inflammatory, anti-oxidant, and anti-cancer properties. The primary goal of the present study was to develop and evaluate eugenol-loaded transethosomes for the treatment of AD. Eugenol-loaded transethosomes were formulated using the ethanol injection method and subsequently subjected to particle size analysis, zeta potential, entrapment efficiency, deformability index, and HRTEM analysis. Transethosomal gel was prepared by direct-dispersion method by using Carbopol 940®. Results showed transethosomes to be lipid bilayer structures with acceptable size, and high entrapment efficiency. Transethosomal formulation showed shear-thinning behavior. Eugenol-loaded transethosomal gel was significantly able to enhance the retention of the drug in the skin. Transethosomal gel was significantly able to reduce Ear thickness, DLC, TLC, and IL-6 levels in mice model of AD. These results indicate that the eugenol-loaded transethosomal gel could be a promising carrier for the topical administration of eugenol for the treatment of AD.

Influence of Different Ratios of DSPE-PEG2k on Ester Prodrug Self-Assembly Nanoparticles for Cell Migration and Proliferation Suppression.

Background: Bufalin (BFL, an active anti-tumor compound derived from toad venom) is limited in its application due to high toxicity and rapid metabolism of the cardiotonic steroid. Ester prodrug self-assembly nanoparticles have shown significant improved effects in addressing the above-mentioned issues. Methods: An ester bond was formed between linoleic acid and bufalin to synthesize linoleic acid-bufalin prodrug (LeB). The self-assembly nanoparticles (LeB-PSNs) containing different mass ratios of DSPE-PEG2k and prodrug (6:4, 7:3, 8:2, 9:1 and 10:0) were prepared via co-precipitation method and defined as 6:4-PSNs, 7:3-PSNs, 8:2-PSNs, 9:1-PSNs and LeB-PSNs, respectively. Further, the characterization (particle size, zeta potential, surface morphology and stability) of the nanoparticles was carried out. Finally, we evaluated the impact of different ratios of DSPE-PEG2k on the hydrolysis rate, cytotoxicity, cellular uptake, cell migration and proliferation suppression potential of the prodrug nanoparticles. Results: The linoleic acid-bufalin prodrug (LeB) was successfully synthesized. Upon the addition of DSPE-PEG2k at different weight ratios, both particle size and polydispersity index (PDI) significantly decreased, while the zeta potential increased remarkably. No significant differences in particle size, PDI and Zeta potential were observed among the 9:1, 8:2 and 7:3 PSNs. Notably, the 8:2 (w/w) DSPE-PEG2k nanoparticles exhibited superior stability, hydrolysis and cellular uptake rates, along with efficient cell cytotoxicity, cell migration and proliferation suppression. Conclusion: These findings indicate that DSPE-PEG2k could improve the performance of BFL prodrug nanoparticles, namely enhancing stability and achieving adaptive drug release by modulating the hydrolysis rate of esterase. This study therefore provides more opportunities for the development of BFL application.

Synergistic effect of mesoporous silica nanocarrier-assisted photodynamic therapy and anticancer agent activity on lung cancer cells.

Investigating combined treatment methodologies is crucial for addressing the complex nature of cancer. As an emerging strategy, nano-biotechnology encourages the design of unique nanocarriers possessing simultaneous therapeutic application properties. This study aims to explore the combined effects of photodynamic and anticancer treatments using a multifunctional nanocarrier system co-administering the photosensitizer IR780 and the anticancer agent curcumin (Cur) on lung cancer cells. Nanocarriers were prepared by encapsulation IR780 and Cur inside polyethylene glycol-capped mesoporous silica nanoparticles (Cur&IR780@MSN). Various concentrations of nanocarriers were evaluated on A549 cells following 5 min NIR laser light (continuous wave, 785 nm, 500 mW/cm2) irradiation. The internalization of nanocarriers was observed through the fluorescence of Cur. Changes in cell viability were determined using the MTT assay and AO/PI staining. A scratch assay analysis was also performed to examine the impact of combined treatments on cell migration. Characterization of the nanocarriers revealed adequate hydrophobic drug loading, temperature-inhibited feature, enhanced reactive oxygen species generation, a pH-dependent curcumin release profile, and high biocompatibility. Cur&IR780@MSN, which enabled the observation of synergistic treatment efficacy, successfully reduced cell viability by up to 78%. In contrast, monotherapies with curcumin-loaded nanocarriers (Cur@MSN) and IR780-loaded nanocarriers (IR780@MSN) resulted in a 38% and 56% decrease in cell viability, respectively. The constructed Cur&IR780@MSN nanocarrier has demonstrated remarkable performance in the application of combination therapies for lung cancer cells. These nanocarriers have the potential to inspire future studies in tumor treatment methods.

Characterization of Drug with Good Glass-Forming Ability Loaded Mesoporous Silica Nanoparticles and Its Impact Toward in vitro and in vivo Studies.

Solid oral dosage forms are mostly preferred in pharmaceutical formulation development due to patient convenience, ease of product handling, high throughput, low manufacturing costs, with good physical and chemical stability. However, 70% of drug candidates have poor water solubility leading to compromised bioavailability. This phenomenon occurs because drug molecules are often absorbed after dissolving in gastrointestinal fluid. To address this limitation, delivery systems designed to improve the pharmacokinetics of drug molecules are needed to allow controlled release and target-specific delivery. Among various strategies, amorphous formulations show significantly high potential, particularly for molecules with solubility-limited dissolution rates. The ease of drug molecules to amorphized is known as their glass-forming ability (GFA). Specifically, drug molecules categorized into class III based on the Taylor classification have a low recrystallization tendency and high GFA after cooling, with substantial "glass stability" when heated. In the last decades, the application of mesoporous silica nanoparticles (MSNs) as drug delivery systems (DDS) has gained significant attention in various investigations and the pharmaceutical industry. This is attributed to the unique physicochemical properties of MSNs, including high loading capacity, recrystallization inhibition, excellent biocompatibility, and easy functionalization. Therefore, this study aimed to discuss the current state of good glass former drug loaded mesoporous silica and shows its impact on the pharmaceutical properties including dissolution and physical stability, along with in vivo study. The results show the importance of determining whether mesoporous structures are needed in amorphous formulations to improve the pharmaceutical properties of drug with a favorable GFA.

Preparation and Evaluation of Folate Modified PEG-PLLA Nanoparticles Loaded with Lycorine for Glioma Treatment.

Lycorine is a kind of natural active ingredient with a strong antitumor effect. In this study, folate ligand-conjugated polyethylene glycol-block-poly(l-lactide) (PEG-PLLA) nanoparticles (FA-PEG-PLLA NPs) were designed to deliver lycorine to enhance its anti-glioma activity. The successful preparation of the FA-PEG-PLLA polymer was confirmed by 1H-NMR, FT-IR, XRD, TGA, and DSC. The optimal formulation for LYC@FA-PEG-PLLA NPs was determined by response surface analysis as follows: sodium dodecyl sulfate (SDS) of 1%, carrier material of 0.03 g, organic phase volume of 3 mL, and ultrasonic power of 20%. The LYC@FA-PEG-PLLA NPs exhibited an encapsulation efficiency of 83.58% and a particle size of 49.71 nm, demonstrating good stability. Hemolysis experiments, MTT assays, and cell scratch assays revealed excellent biocompatibility of FA-PEG-PLLA and superior anti-glioma activity of LYC@FA-PEG-PLLA NPs compared to the raw drug. Additionally, cell apoptosis assays, ROS experiments, and western blot analysis demonstrated that LYC@FA-PEG-PLLA NPs contributed to cell apoptosis by inducing ROS generation and increasing the expression of NF-κB inhibitory protein IκBα. These results suggested that LYC@FA-PEG-PLLA NPs hold promise for glioma treatment.

Hydrogen-bonded cytosine-endowed supramolecular polymeric nanogels: Highly efficient cancer cell targeting and enhanced therapeutic efficacy.

We demonstrate that cytosine moieties within physically cross-linked supramolecular polymers not only manipulate drug delivery and release, but also confer specific targeting of cancer cells to effectively enhance the safety and efficacy of chemotherapy-and thus hold significant potential as a new perspective for development of drug delivery systems. Herein, we successfully developed physically cross-linked supramolecular polymers (PECH-PEG-Cy) comprised of hydrogen-bonding cytosine pendant groups, hydrophilic poly(ethylene glycol) side chains, and a hydrophobic poly(epichlorohydrin) main chain. The polymers spontaneously self-assemble into a reversibly hydrogen-bonded network structure induced by cytosine and directly form spherical nanogels in aqueous solution. Nanogels with a high hydrogen-bond network density (i.e., a higher content of cytosine moieties) exhibit outstanding long-term structural stability in cell culture substrates containing serum, whereas nanogels with a relatively low hydrogen-bond network density cannot preserve their structural integrity. The nanogels also exhibit numerous unique physicochemical characteristics in aqueous solution, such as a desirable spherical size, high biocompatibility with normal and cancer cells, excellent drug encapsulation capacity, and controlled pH-responsive drug release properties. More importantly, in vitro experiments conclusively indicate the drug-loaded PECH-PEG-Cy nanogels can selectively induce cancer cell-specific apoptosis and cell death via cytosine receptor-mediated endocytosis, without significantly harming normal cells. In contrast, control drug-loaded PECH-PEG nanogels, which lack cytosine moieties in their structure, can only induce cell death in cancer cells through non-specific pathways, which significantly inhibits the induction of apoptosis. This work clearly demonstrates that the cytosine moieties in PECH-PEG-Cy nanogels confer selective affinity for the surface of cancer cells, which enhances their targeted cellular uptake, cytotoxicity, and subsequent induction of programmed cell death in cancer cells.

Exploring oral drug delivery: In vitro release and mathematical modeling of hydrophobic drug (Na-L-thyroxine) and its cyclodextrin inclusion complex in chitosan microparticles.

Na-l-Thyroxine (Na-l-Thy) is a frequently prescribed synthetic hormone for hypothyroidism treatment. Despite its efficacy, its hydrophobic nature poses a challenge for achieving optimal bioavailability. To address this, researchers explored various delivery methods, including micro-formulations and nano-formulations, for precise and prolonged release of hydrophobic and hydrophilic drugs. In this study, we developed micro-formulations with cyclodextrin and chitosan. Docking studies identified γ-cyclodextrin as the preferred option for forming a stable complex with Na-l-Thyroxine compared to α, and ß-cyclodextrins. Two micro-formulations were prepared compared: Na-l-Thyroxine loaded on chitosan (CS + Na-l-Thy) and Na-l-Thyroxine and γ-cyclodextrin inclusion complex (IC) loaded on chitosan (CS + IC). CS + IC exhibited superior encapsulation efficiency (91.25 %) and loading capacity (18.62 %) compared to CS + Na-l-Thy (encapsulation efficiency: 70.24 %, loading capacity: 21.18 %). Characterization using FTIR, SEM, and TGA validated successful encapsulation of Na-l-Thy in spherical microparticles with high thermal stability. In-vitro release studies at pH 1.2 and 7.4 showed that the CS + IC microparticles displayed gradual, consistent drug release compared to CS + Na-l-Thy -Thy. Both formulations showed faster release at pH 1.2 than at pH 7.4. Reaction kinetics analysis of release studies of CS + Na-l-Thy and CS + IC were best described by Higuchi kinetic model and Korsemeyer-Peppas kinetic model respectively. This study suggests that the CS + IC microparticles are an effective and stable delivery system for sustained release of hydrophobic Na-l-Thy.

Bioreducible Amphiphilic Hyperbranched Polymer-Drug Conjugate for Intracellular Drug Delivery.

This paper reports synthesis of a bioreducible hyperbranched (HB) polymer by A2+B3 approach from commercially available dithiothreitol (DTT) (A2) and an easily accessible trifunctional monomer (B3) containing three reactive pyridyl-disulfide groups. Highly efficient thiol-activated disulfide exchange reaction leads to the formation of the HB polymer (Mw = 21000; D = 2.3) with bioreducible disulfide linkages in the backbone and two different functional groups, namely, hydroxyl and pyridyl-disulfide in the core and periphery, respectively, of the HB-polymer. Postpolymerization functionalization of the hydroxyl-groups with camptothecin (CPT), a topoisomerase inhibitor and known anticancer drug, followed by replacing the terminal pyridyl-disulfide groups with oligo-oxyethylene-thiol resulted in easy access to an amphiphilic HB polydisulfide-CPT conjugate (P1) with a very high drug loading content of ∼40%. P1 aggregated in water (above ∼10 µg/mL) producing drug-loaded nanoparticles (Dh ∼ 135 nm), which showed highly efficient glutathione (GSH)-triggered release of the active CPT. Mass spectrometry analysis of the GSH-treated P1 showed the presence of the active CPT drug as well as a cyclic monothiocarbonate product, which underpins the cascade-degradation mechanism involving GSH-triggered cleavage of the labile disulfide linkage, followed by intramolecular nucleophilic attack by the in situ generated thiol to the neighboring carbonate linkage, resulting in release of the active CPT drug. The P1 nanoparticle showed excellent cellular uptake as tested by confocal fluorescence microscopy in HeLa cells by predominantly endocytosis mechanism, resulting in highly efficient cell killing (IC50 ∼ 0.6 µg/mL) as evident from the results of the MTT assay, as well as the apoptosis assay. Comparative studies with an analogous linear polymer-CPT conjugate showed much superior intracellular drug delivery potency of the hyperbranched polymer.

Multifunctional thiolated chitosan/puerarin composite hydrogels with pH/glutathione dual responsiveness for potential drug carriers.

Puerarin (PUE), a natural and biologically active isoflavone extracted from Chinese medicine Pueraria lobata, can self-assemble to form a hydrogel without other chemical modifications. However, although PUE hydrogel has pH responsivity, but it is difficult to adapt to the changeable pathological environment. Therefore, thiolated chitosan (TCS) is synthesized and hybridized with PUE hydrogel to prepare TCS10/PUE composite hydrogel. The results of rheological measurement showed that the resultant composite hydrogels inherited the low loss performance of TCS hydrogel, which means that they have stronger elasticity. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images displayed that TCS10/PUE composite hydrogel has a fibrous-network structure. X-Ray Diffractometer (XRD) and Fourier transform infrared spectroscopy (FT-IR) proved the existence of hydrogen bonds and disulfide bonds in the formation of composite hydrogel. Degradation experiment showed that TCS10/PUE composite hydrogels have pH and glutathione (pH/GSH) dual sensitivity. Furthermore, TCS10/PUE composite hydrogels exhibited multi-functionality including thixotropy, cytocompatibility, antibacterial and anti-inflammatory properties. Berberine chloride hydrate (BCH) was further used as a model drug for in vitro release study. BCH and PUE could be released cooperatively under pH/GSH dual responsivity. These results indicated that the resultant composite hydrogel has eminent pH/GSH dual responsivity and could act as a potential new intelligent drug carrier.

Chitosan and sodium alginate nanocarrier system: Controlling the release of rapeseed-derived peptides and improving their therapeutic efficiency of anti-diabetes.

Rapeseed-derived peptides (RPPs) can maintain the homeostasis of human blood glucose by inhibiting Dipeptidyl Peptidase-IV (DPP-IV) and activating the calcium-sensing receptor (CaSR). However, these peptides are susceptible to hydrolysis in the gastrointestinal tract. To enhance the therapeutic potential of these peptides, we developed a chitosan/sodium alginate-based nanocarrier to encapsulate two RPP variants, rapeseed-derived cruciferin peptide (RCPP) and rapeseed-derived napin peptide (RNPP). A convenient three-channel device was employed to prepare chitosan (CS)/sodium alginate (ALG)-RPPs nanoparticles (CS/ALG-RPPs) at a ratio of 1:3:1 for CS, ALG, and RPPs. CS/ALG-RPPs possessed optimal encapsulation efficiencies of 90.7 % (CS/ALG-RNPP) and 91.4 % (CS/ALG-RCPP), with loading capacities of 15.38 % (CS/ALG-RNPP) and 16.63 % (CS/ALG-RCPP) at the specified ratios. The electrostatic association between CS and ALG was corroborated by zeta potential and near infrared analysis. 13C NMR analysis verified successful RPPs loading, with CS/ALG-RNPP displaying superior stability. Pharmacokinetics showed that both nanoparticles were sustained release and transported irregularly (0.43 < n < 0.85). Compared with the control group, CS/ALG-RPPs exhibited significantly increased glucose tolerance, serum GLP-1 (Glucagon-like peptide 1) content, and CaSR expression which play pivotal roles in glucose homeostasis (*p < 0.05). These findings proposed that CS/ALG-RPPs hold promise in achieving sustained release within the intestinal epithelium, thereby augmenting the therapeutic efficacy of targeted peptides.

Design and Development of Gold/reduced Graphene Oxide Nanocomposite loaded with Cyclophosphamide: Potential Application in Treatment of Breast Cancer.

OBJECTIVE: Cyclophosphamide (CP) is a widely used anti-cancer drug. It works by alkylation and is commonly used in cancer treatment. In this study, the goal was to create biodegradable drug delivery carriers with minimal side effects for breast cancer treatment by developing gold nanoparticles/reduced graphene oxide (Au-rGO) nanocomposites using a sustainable synthesis method and loading them with cyclophosphamide. METHODS: Cyclophosphamide-loaded gold/reduced graphene oxide nanocomposites (Au-rGOCP) were synthesized and evaluated using FT-IR, XRD, release pattern, and FE-SEM techniques. Furthermore, the anticancer effect against breast cancer cells was evaluated through MTT and Annexin V assays. CAT, SOD, and GPx biomarkers were used to assess the antioxidant effect of the free and nano-formulated cyclophosphamide. RESULTS: The characterization results showed the effective loading of cyclophosphamide in the nanocarriers. Additionally, Au-rGO had a higher drug loading capacity for cyclophosphamide during a 24-hour contact period (92.34%). The pH value affected the amount of cyclophosphamide released from the nanocarriers. Au-rGO/CP displayed significant in vitro anti-cancer activity against MCF-7 cancer cells relative to free CP and rGO/CP. According to Annexin V assay results, Au-rGO/CP induced a higher apoptosis rate in MCF-7 breast cancer cells than other forms. CONCLUSION: In conclusion, our findings demonstrate that the gold-decorated reduced graphene oxide nanocomposite enhances treatment efficacy and significantly increases apoptosis and cell death induction. As a result, CP-loaded Au-rGO-based compounds could be a promising treatment for breast cancer.

Fabrication of Microalgae Oil Vesicles for Drug Delivery Applications.

In this study, it is demonstrated that natural microalgae oils, which contain fatty acid components including docosahexaenoic acid (DHA), could be directly applied to fabricate vesicular structures in aqueous phase through a forced formation process. The microalgae oil vesicles had initial average diameters of 170- 230 nm with negative charges apparently caused by dissociation of the fatty acid components. The vesicles possessed excellent stability with lifetimes for at least 450 days. The formation of the vesicular structures with hydrophilic cores/regions was confirmed by the transmission electron microscopy (TEM) image and successful encapsulation of a hydrophilic material. For encapsulation of a hydrophobic material, lutein, the vesicle size was increased probably due to the insertion of lutein into the hydrophobic vesicular bilayer structures. The analysis of Fourier transform infrared (FTIR) spectroscopy suggested that the vesicular bilayer fluidity was decreased by encapsulating lutein. However, the lutein-encapsulating microalgae oil vesicles still possessed high stability and the vesicular structures could maintain intact even at an environmental temperature up to 60℃. Applicability of the microalgae oil vesicles as drug delivery carriers was also demonstrated by successful encapsulation of curcumin. However, when the loaded curcumin was increased to a certain amount, physical stability of the microalgae oil vesicles was significantly reduced. This is probably because the vesicular structures with only limited spaces for accommodating hydrophobic materials were strongly affected by encapsulating a large amount of curcumin. It is interesting to note that by adding egg L-α-phosphatidylcholine, the curcumin encapsulation-induced instability of the microalgae oil vesicles could be alleviated. The results indicated that vesicular structures could be fabricated from microalgae oils and the microalgae oil vesicles were capable of encapsulating hydrophilic or hydrophobic materials for drug delivery applications. The findings lay a background for further dosage form development of nutritional supplements encapsulated by natural microalgae oils.

Selective Anticervical Cancer Injectable and Self-Healable Hydrogel Platforms Constructed of Drug-Loaded Cross-Linkable Unimolecular Micelles in a Single and Combination Therapy.

In the face of severe side effects of systemic chemotherapy used in cervical cancer, topical selective drug carriers with long-lasting effects are being sought. Hydrogels are suitable platforms, but their use is problematic in the case of delivery of hydrophobic drugs with anticancer activity. Herein, hydrogels constructed of unimolecular micelles displaying enhanced solubilization of aromatic lipophilic bioactive compounds are presented. Star-shaped poly(benzyl glycidyl ether)-block-poly(glycidyl glycerol ether) with an aryl-enriched core show high encapsulation capacity of poor water-soluble nifuratel and clotrimazole. Nifuratel attained selectivity against cervical cancer cells, whereas clotrimazole preserved its original selectivity. The combination of unimolecular micelles loaded with both drugs provided synergism; however, they were still selective against cervical cancer cells. The cross-linking of drug-loaded unimolecular micelles via dynamic boronic esters provided injectable and self-healable hydrogel drug carriers also displaying synergistic anticancer activity, suitable for intravaginal administration and assuring the effective coverage of the afflicted tissue area and efficient tissue permeability with hydrophobic bioactive compounds. Here, we show that the combination of star-shaped polyether amphiphiles and boronic ester cross-linking chemistry provides a new strategy for obtaining hydrogel platforms suitable for efficient hydrophobic drug delivery.

Polyurethane Microstructures for 2'-Deoxycytidinic Acid Delivery: Preparation and Preliminary Characterization.

Background and Objectives: Nucleotide delivery has emerged as a noteworthy research trend in recent years because of its potential utility in addressing a range of genetic defects resulting in the presence of incorrect nucleotides. The primary goals of this research were to create and to characterize polyurethane microstructures, with the aim of utilizing them for nucleotide transport. Materials and Methods: Two samples were prepared using an aliphatic diisocyanate in reaction with a mixture of polyethylene glycol and polycaprolactone diol, where 2'-deoxycytidinic acid was used as the active agent and glycerol 1,2-diacetate was used as an enhancer of the aqueous solubility. The solubility, pH, size distribution, and surface charge of the samples were measured, and encapsulation efficacy and release, cell proliferation, and irritation tests on mouse skin were conducted. Results: The results showed almost neutral acidic-basic structures with a high heterogeneity, and a medium tendency to form clusters with non-cytotoxic and non-irritative potentials. Conclusions: Future research could explore the efficacy of this carrier in delivering other nucleotides, as well as investigating the long-term effects and safety of these microstructures in vivo.

Core-Shell Structure of Photopolymer-Grafted Polyurethane as a Controlled Drug Delivery Vehicle for Biomedical Application.

Functionalized ultraviolet photocurable bisphenol A-glycerolate dimethacrylates with tailorable size have been synthesized as the core, which have further been grafted using the diisocyanate chain end of polyurethane (PU) as the shell to create a core-shell structure of tunable size for a controlled drug delivery vehicle. The core-shell structure has been elucidated through spectroscopic techniques like 1H NMR, FTIR, and UV-vis and their relative shape and size through TEM and AFM morphology. The greater cross-link density of the core is reflected in the higher glass transition temperature, and the improved thermal stability of the graft copolymer is proven from its thermogravimetric analyses. The flow behavior and enhanced strength of the graft copolymers have been revealed from rheological measurements. The graft copolymer exhibits sustained release of the drug, as compared to pure polyurethane and photopolymer, arising from its core-shell structure and strong interaction between the copolymer and drug, as observed through a significant shifting of absorption peaks in FTIR and UV-vis measurements. Biocompatibility has been tested for the real application of the novel graft copolymer in medical fields, as revealed from MTT assay, cell imaging, and cell adhesion studies. The efficacy of controlled release from a graft copolymer has been verified from the gradual cell killing and ∼70% killing in 3 days vs meager cell killing of ∼25% very quickly in 1 day, followed by the increased cell viability of the system treated with the pure drug. The mechanism of slow and controlled drug release from the core-shell structure has been explored. The fluorescence images support the higher cell-killing efficiency as opposed to a pure drug or a drug embedded in polyurethane. Cells seeded on 3D scaffolds have been developed by embedding a graft copolymer, and fluorescence imaging confirms the successful growth of cells within the scaffold, realizing the potential of the core-shell graft copolymer in the biomedical arena.

PEGylated mesoporous silica core-shell redox-responsive nanoparticles for delivering paclitaxel to breast cancer cells.

Controlling the drug release and restricting its presence in healthy organs is extremely valuable. In this study, mesoporous silica nanoparticles (MSN) as the core, loaded with paclitaxel (PTX), were coated with a non-porous silica shell functionalized with disulfide bonds. The nanoparticles were further coated with polyethylene glycol (PEG) via disulfide linkages. We analyzed the physicochemical properties of nanoparticles, including hydrodynamic size via Dynamic Light Scattering (DLS), zeta potential, X-ray Diffraction (XRD) patterns, Fourier-Transform Infrared (FTIR) spectra, and imaging through Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The drug release profile in two distinct glutathione (GSH) concentrations of 2 µM and 10 µM was measured. The cellular uptake of nanoparticles by MCF-7 cell line was determined using Confocal Laser Scanning Microscopy (CLSM) images and flow cytometry. Furthermore, the cell viability and the capability of nanoparticles to induce apoptosis in MCF-7 cell line were studied using the MTT assay and flow cytometry, respectively. Our investigations revealed that the release of PTX from the drug delivery system was redox-responsive. Also, results indicated an elevated level of cellular uptake and efficient induction of apoptosis, underscoring the promising potential of this redox-responsive drug delivery system for breast cancer therapy.