Drug Encapsulation Efficiency Research Articles

Gaussian processes modeling for the prediction of polymeric nanoparticle formulation design to enhance encapsulation efficiency and therapeutic efficacy.

Conventional drugs have been facing various drug delivery obstacles, including first-pass metabolism for oral medications, drug degradation by cellular enzymes, off-target effects, and cytotoxicity of healthy cells. Nanoparticles (NP) application in drug delivery can compensate for these drawbacks to a great extent. NPs can be fabricated using different materials and structures to achieve desired therapeutic effects. For each type of NP material, its physicochemical properties determine compatibility with specific drugs and other supplemental compositions. The optimized material selection becomes prominent in NP development to improve NP performances. Due to the nature of NP fabrication, the process is long and expensive. To accelerate NP composition optimization, machine learning (ML) techniques are among the most promising methods for efficient data predictions and optimizations.As a proof-of concept, we created Gaussian Process (GP) models to make predictions for drug encapsulation efficiency (EE%) and therapeutic efficacy of 32 poly (lactic-co-glycolic acid) (PLGA) NPs that are formed with materials with different physicochemical properties. Two model drugs, doxorubicin (DOX) and docetaxel (DTX) were loaded separately. The IC50 values for the various NPs formulations were evaluated using the OVCAR3 epithelial ovarian cancer cell line. EE% GP model has the highest prediction accuracy with the lowest normalized root-mean-squared-error (RMSE) of 0.187. The DOX and DTX IC50 GP models have normalized RMSEs of 0.296 and 0.206, respectively, which are higher than that of the EE% GP model.

Antiepileptic drug-loaded and multifunctional iron oxide@silica@gelatin nanoparticles for acid-triggered drug delivery.

The current study developed an innovative design for the production of smart multifunctional core-double shell superparamagnetic nanoparticles (NPs) with a focus on the development of a pH-responsive drug delivery system tailored for the controlled release of Phenytoin, accompanied by real-time monitoring capabilities. In this regard, the ultra-small superparamagnetic iron oxide@silica NPs (IO@Si MNPs) were synthesized and then coated with a layer of gelatin containing Phenytoin as an antiepileptic drug. The precise saturation magnetization value for the resultant NPs was established at 26 emu g-1. The polymeric shell showed a pH-sensitive behavior with the capacity to regulate the release of encapsulated drug under neutral pH conditions, simultaneously, releasing more amount of the drug in a simulated tumorous-epileptic acidic condition. The NPs showed an average size of 41.04nm, which is in the desired size range facilitating entry through the blood-brain barrier. The values of drug loading and encapsulation efficiency were determined to be 2.01 and 10.05%, respectively. Moreover, kinetic studies revealed a Fickian diffusion process of Phenytoin release, and diffusional exponent values based on the Korsmeyer-Peppas equation were achieved at pH 7.4 and pH 6.3. The synthesized NPs did not show any cytotoxicity. Consequently, this new design offers a faster release of PHT at the site of a tumor in response to a change in pH, which is essential to prevent epileptic attacks.

Celastrol-loaded polymeric mixed micelles shows improved antitumor efficacy in 4 T1 bearing xenograft mouse model through spatial targeting.

In this study, we have proposed a novel approach that combines hyaluronic acid (HA), folic acid (FA), and celastrol (CLS) within a polymeric micelle system (HF-CLS/MLs), offering a dual-action strategy against breast cancer. Polymeric mixed micelles were prepared through the thin-film hydration method, and comprehensive quality control parameters were established, encompassing particle size, polydispersity index, zeta potential, surface morphology, encapsulation efficiency, drug content, in vitro drug release, and storage stability assessment. The average particle size of CLS-HF/MLs micelles was found to be 120 nm and their drug loading and encapsulation efficiencies were 15.9 % and 89.52 %, respectively. The in vitro release data showed that the CLS-HF/MLs targeted mixed micelles displayed a prolonged release profile compared to the free drug. Additionally, the stability of the developed polymeric mixed micelles was maintained for up to 8 weeks of storage in terms of particle size and drug content. Furthermore, both flow cytometry and confocal laser scanning microscopy studies indicated a significant enhancement in the cellular uptake efficiency and cytotoxicity of CLS-HF/MLs mixed micelles against MCF-7 cell line. In terms of pharmacokinetic analysis, the half-life and AUC values of CLS-HF/MLs mixed micelles were found to be approximately 4.71- and 7.36-folds higher than the values of free drug (CLS), respectively. The CLS-HF/MLs micelles exhibited remarkable antitumor efficacy (almost complete ablation of the 4 T1-cell bearing tumor xenografts mouse model) due to the dual receptor (CD44 and folate) targeting effects with minimal side effects. When considering the cumulative findings of our present research, it becomes evident that mixed micelles designed for chemotherapy offer a promising and potentially effective therapeutic avenue for the treatment of breast cancer.

Production of PEGylated Vancomycin-Loaded Niosomes by a Continuous Supercritical CO2 Assisted Process

Niosomes are arousing significant interest thanks to their low cost, high biocompatibility, and negligible toxicity. In this work, a supercritical CO2-assisted process was performed at 100 bar and 40 °C to produce niosomes at different Span 80/Tween 80 weight ratios. The formulation of cholesterol and 80:20 Span 80/Tween 80 was selected to encapsulate vancomycin, used as a model active compound, to perform a drug release rate comparison between PEGylated and non-PEGylated niosomes. In both cases, nanometric vesicles were obtained, i.e., 214 ± 59 nm and 254 ± 73 nm for non-PEGylated and PEGylated niosomes, respectively, that were characterized by a high drug encapsulation efficiency (95% for non-PEGylated and 98% for PEGylated niosomes). However, only PEGylated niosomes were able to prolong the vancomycin release time up to 20-fold with respect to untreated drug powder, resulting in a powerful strategy to control the drug release rate.

Fabrication of biocompatible water-soluble supramolecular nanofibers of oseltamivir with methyl-β-cyclodextrin for enhanced drug release

In recent times, there has been a growing interest in the advancement of nanofiber technology using materials based on cyclodextrin (CD). This heightened interest is primarily driven by their potential applications in controlled drug release. This research aims to create the nanofibers (NF) which involves incorporating an antiviral agent, oseltamivir (OTV) into the CD cavity, forming inclusion complexes (IC) that greatly improve drug encapsulation efficiency. To assess the physicochemical properties and drug-loading capabilities of these CD-based NF, a variety of characterization techniques can be utilized. It is noteworthy that NF containing OTV:MCD-IC/PVA demonstrates a continuous release of OTV (89.25%) at acidic conditions (pH 5.8) when compared to NF holding no MCD materials. Moreover, dissolution studies reveal that the resulting material is non-toxic and readily soluble in water (less than 2 min). MTT assay indicated that the examined NF are completely safe and do not have/make any adverse effects on the cells (cell viability is more than 98%). The fibroblast cells grown on nanomatrixes composed of both OTV/PVA and OTV:MCD IC/PVA NF did not display any indications of apoptosis or nuclear shrinkage. The development of such systems holds significant promise for advancing therapeutic strategies in the management of viral infections.

Dual ionotropic crosslinked biopolymer magnetic nanocomposites as 5‐Fluorouracil nanocarrier for potential colorectal cancer treatment

AbstractThis study aimed to synthesize dual‐crosslinked chitosan‐alginate nanocomposites (Cs‐Alg/IO NCs) using green‐synthesized iron oxide nanoparticles (IO, Fe3O4 NPs) for drug delivery application. The NCs, formed via ionotropic gelation with sodium tripolyphosphate (TPP) and calcium chloride (CaCl2) as crosslinking agents for Cs and Alg, respectively, and further characterized for physiochemical properties. The presence of Fe3O4 NPs and 5‐Fluorouracil (5FU) increased hydrodynamic size (153.12 ± 0.57 to 207.64 ± 3.59 nm). Morphological studies revealed NC agglomeration within nanoscales. 5FU‐loaded Cs‐Alg/IO NCs (Cs‐Alg/IO 5FU NCs) exhibited superparamagnetic behavior and sustained drug release under various pH conditions. Cytotoxicity assays on colon cancer cells (HCT116 and HT‐29) and normal colon cells (CCD‐112) indicated higher cancer cell selectivity (selectivity index, SI = 1.91) in 2D models. Elevated IC50 values in 3D models were linked to lower drug loading capacity (LC) and encapsulation efficiency (EE). Overall, the study highlights the potential of dual‐crosslinked biopolymer NCs with green‐synthesized Fe3O4 NPs for developing an anticancer drug delivery system in colorectal cancer treatment.Highlights Synthesis of 5FU‐loaded dual crosslinked Cs‐Alg/IO NCs and Cs‐Alg IPN. Physicochemical characterization of cross‐linked magnetic nanocarriers. Investigation of sustained drug release using superparamagnetic nanocarriers. Evaluation of selective cytotoxicity for Cs‐Alg/IO 5FU NCs.

Development of 1 Month Sustained-Release Microspheres Containing Liraglutide for Type 2 Diabetes Treatment.

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus (T2DM), but its 11-15 h half-life resulted in daily administration, which led to poor patient compliance. This study aimed to solve this problem by developing liraglutide-loaded microspheres with a 1 month sustained release prepared by the W1/O/W2 method combined with the premix membrane emulsification technique to improve therapeutic efficacy. Remarkably, we found that the amphiphilic properties of liraglutide successfully reduced the oil-water interfacial tension, resulting in a stable primary emulsion and decreasing the level of drug leakage into the external water phase. As a result, exceptional drug loading (>8%) and encapsulation efficiency (>85%) of microspheres were achieved. Furthermore, the uniformity in microsphere size facilitated an in-depth exploration of the structural characteristics of liraglutide-loaded microspheres. The results indicated that the dimensions of the internal cavities of the microspheres were significantly influenced by the size of the inner water droplets in the primary emulsion. A denser and more uniform cavity structure decreased the initial burst release, improving the release process of liraglutide from the microspheres. To evaluate the release behavior of liraglutide from microspheres, a set of in vitro release assays and in vivo pharmacodynamics were performed. The liraglutide-loaded microspheres effectively decreased fasting blood glucose (FBG) levels and hemoglobin A1c (HbA1c) levels while enhancing the pancreatic and hepatic functions in db/db mice. In conclusion, liraglutide sustained-release microspheres showed the potential for future clinical applications in the management of T2DM and provided an effective therapeutic approach to overcoming patient compliance issues.

Kinetic and Mechanism of Zerumbone Release from Cross-linked Gelatin-Zeolite Y Hybrid for Oral Anticancer Drug Delivery

A hybrid of zeolite Y-gelatin film as an oral dosage form for the natural anticancer drug was achieved by homogenously incorporating the drug-loaded zeolite Y into the gelatin solution. Drug ability was analyzed using computational and experimental approaches, drug encapsulation efficiency via the BET method, and possible interactions by FTIR analyses. Zerumbone released was done in both pH 1.2 and pH 7.4 mimicking the human gastrointestinal tract conditions for 24 hrs and subjected to kinetics study via suitable mathematical models to determine what governs the drug release with the results indicating that a sustained delivery of once-daily oral dosage form could be achieved.

Delivery of Chlorambucil to the Brain Using Surface Modified Solid Lipid Nanoparticles.

The delivery of drugs to the brain in the therapy of diseases of the central nervous system (CNS) remains a continuing challenge because of the lack of delivery systems that can cross the blood-brain barrier (BBB). Therefore, there is a need to develop an innovative delivery method for the treatment of CNS diseases. Thus, we have investigated the interaction of γ-aminobutyric acid (GABA) and S-(-)-γ-amino-α-hydroxybutyric acid (GAHBA) with the GABA receptor by performing a docking study. Both GABA and GAHBA show comparable binding affinities toward the receptor. In this study, we developed surface-modified solid lipid nanoparticles (SLNs) using GAHBA-derived lipids that can cross the BBB. CLB-loaded SLNs were characterized by a number of methods including differential scanning calorimetry, dynamic light scattering, UV-vis spectroscopy, and transmission electron microscopy. The blank and CLB-loaded SLN suspensions were found to exhibit good storage stability. Also, the SLNs showed a higher encapsulation efficiency for CLB drugs. In vitro release kinetics of CLB at physiological temperature was also investigated. The results of the in vitro cell cytotoxicity assay and flow cytometry studies in the human glioma U87MG cell line and human prostate cancer PC3 cell line suggested a higher efficacy of the GAHBA-modified CLB-loaded SLNs in U87MG cells. The transcription level of GABA receptor expression in the target organ and cell line was analyzed by a reverse transcription polymerase chain reaction study. The in vivo biodistribution and brain uptake in C57BL6 mice and SPECT/CT imaging in Wistar rats investigated using 99mTc-labeled SLN and autoradiography suggest that the SLNs have an increasing brain uptake. We have demonstrated the delivery of the anticancer drug chlorambucil (CLB) to glioma.

Polycaprolactone – Vitamin E TPGS micelles for delivery of paclitaxel: In vitro and in vivo evaluation

This study aimed to present findings on a paclitaxel (PTX)-loaded polymeric micellar formulation based on polycaprolactone-vitamin E TPGS (PCL-TPGS) and evaluate its in vitro anticancer activity as well as its in vivo pharmacokinetic profile in healthy mice in comparison to a marketed formulation. Micelles were prepared by a co-solvent evaporation method. The micelle's average diameter and polydispersity were determined using dynamic light scattering (DLS) technique. Drug encapsulation efficiency was assessed using an HPLC assay. The in vitro cytotoxicity was performed on human breast cancer cells (MCF-7 and MDA-MB-231) using MTT assay. The in vivo pharmacokinetic profile was characterized following a single intravenous dose of 4 mg/kg to healthy mice. The mean diameters of the prepared micelles were ≤ 100 nm. Moreover, these micelles increased the aqueous solubility of PTX from ~0.3 μg/mL to reach nearly 1 mg/mL. While the PTX-loaded micelles showed an in vitro cytotoxicity comparable to the marketed formulation (Ebetaxel), drug-free PCL-TPGS micelles did not show any cytotoxic effects on both types of breast cancer cells (~100% viability). Pharmacokinetics of PTX as part of PCL-TPGS showed a significant increase in its volume of distribution compared to PTX conventional formulation, Ebetaxel, which is in line with what was reported for clinical nano formulations of PTX, i.e., Abraxane, Genexol-PM, or Apealea. The findings of our studies indicate a significant potential for PCL-TPGS micelles to act as an effective system for solubilization and delivery of PTX.

Doxorubicin encapsulated blend of sitagliptin-lignin polymeric drug delivery system for effective combination therapy against cancer

In this research, a sitagliptin-lignin biopolymer (SL) containing zinc selenide quantum dots (ZnSe QDs) and doxorubicin (doxo) was synthesized. The fabricated polymeric drug delivery system was characterized via FTIR, XRD, SEM, TGA, IR, and DSC. SLQD-Doxo exhibited an irregular surface with a 32 nm diameter and well-defined surface chemistry. Drug loading efficiency was assessed at different concentrations, pH levels, time intervals, and temperatures, and drug kinetics were calculated. Maximum drug release was observed at 6 μmol concentration after 24 h, pH of 6.5 and 45 °C. The maximum drug encapsulation efficiency was 81.75 %. SLQD-Doxo demonstrated 24.4 ± 1.04 % anti-inflammatory activity, and the maximum lipoxygenase inhibition in a concentration-dependent manner was 71.45 ± 2.02 %, compared to indomethacin, a standard anticancer drug. The designed system was applied to breast cancer MCF-7 cells to evaluate anticancer activity. Cytotoxicity of SLQD-Doxo resulted in 24.48 ± 1.64 dead cells and 74.39 ± 4.12 viable cells. Lignin's polyphenolic nature resulted in good antioxidant activity of LLQD-Doxo. The combination of SLQD-Doxo was appropriate for drug delivery at high temperatures and acidic pH of tumor cells compared to healthy cells.

Exploring the Antitumor Efficacy of PEGylated Liposomes Loaded with Licorice Extract for Cancer Therapy.

Glycyrrhizic Acid (GA), a compound derived from licorice, has exhibited promising anticancer properties against several cancer types, including Prostate Cancer (PCa) and Gastric Cancer (GCa). This study has introduced a novel approach involving the encapsulation of GA and Licorice extract (Lic) into Polyethylene Glycol Liposomes (PEG-Lip) and assessed their efficacy against AGS (human gastric cancer) and PC-3 (human prostate cancer) cells, marking the first report of this endeavor. We synthesized GA-loaded PEG-Lip (GA PEG-Lip) and Lic-loaded PEG-Lip (Lic PEG-Lip) through the reverse-phase evaporation method. Characterization of these liposomal formulations revealed their size, drug encapsulation, and loading efficiencies to be 110 ± 2.05 nm, 117 ± 1.24 nm; 61 ± 0.81%, 34 ± 0.47%; and 8 ± 0.41% and 4.6 ± 0.21%, respectively. Importantly, the process has retained the chemical structure of both GA and Lic. Furthermore, GA and Lic have been released from the PEG-Lip formulations in a controlled manner. In our experiments, both nanoformulations exhibited enhanced cytotoxic effects against AGS and PC-3 cells. Notably, GA PEG-Lip outperformed Lic PEG-Lip, reducing the viability of PC-3 and AGS cells by 12.5% and 15.9%, respectively. These results have been corroborated by apoptosis assays, which have demonstrated GA PEG-Lip and Lic PEG-Lip to induce stronger apoptotic effects compared to free GA and Lic on both PC-3 and AGS cells. This study has underscored the potential of encapsulating GA and Lic in PEG-Lip as a promising strategy to augment their anticancer efficacy against prostate and gastric cancers.

In silico modeling, development, characterization, in-vitro cytotoxicity, pharmacokinetic, and toxicological studies of folate-receptor targeted micelles containing cisplatin and upconversion nanoparticles for lung cancer therapy

Folate receptor α (FRα) is one of the best motifs to recognize lung cancer, therefore it can be utilized for targeted delivery of therapeutic agents in lung cancer therapy. Herein, we developed folate-receptor-targeted micelles (CPTT-FA) for the co-delivery of cisplatin (CDDP) and upconversion nanoparticles (UCNP) as theranostics for lung cancer therapy. Initially, the binding affinity of FRα (4MK6) was studied, resulting in good docking scores of −7.6 towards 4MK6 by stimulating PI3K inhibition in lung cancer cells. Micelles, fabricated using the solvent-casting technique, exhibited favorable characteristics, including an average size ranging from 80 to 190 nm with a narrow size distribution and spherical morphology. The zeta potential of −29.4 mV indicates stability and potential for targeted delivery. The drug encapsulation efficiency of the micelles was high, ranging from 70 % to 90 %. In vitro, release studies demonstrated an initial burst release of 40 % within 4 h, the release rate was controlled up to 72 h in PBS at pH 6.8. Afterthat, IC50 of the CPTT-FA micelles was found to be 11.6-fold lower than Ciszest-50. Heamolysis study has proven the greater biocompatibility of CPTT-FA. Pharmacokinetic investigations exhibited a significant enhancement with a three-fold increase in the area under the concentration-time curve (AUC0-t) and a 3.7-fold extension in half-life (t1/2). CDDP resistance in lung cancer presents a promising avenue for targeted therapy using UCNP, addressing challenges posed by FRα-positive cases and improving prognosis. Further clinical investigations are needed to validate the effectiveness and safety of this approach before its widespread implementation.

High throughput microfluidics-based synthesis of PEGylated liposomes for precise size control and efficient drug encapsulation

The low scalability and reproducibility of existing synthesis methods have hindered the translation of liposome nanoparticles as carriers for targeted drug delivery from conventional laboratory techniques to mass production. To this end, in this study, we present a high-throughput microfluidics-based approach for the synthesis of PEGylated liposomes with a primary focus on achieving precise size control and efficient encapsulation of hydrophobic drug molecules. In this platform, liposomes were self-assembled through a controllable mixing of lipids (EYPC, cholesterol, and DSPE-PEG 2000) dissolved in ethanol and an aqueous solution. The key parameters, including the chip design, total flow rate, flow rate ratio, lipid concentrations, as well as variations in buffer (HEPES and NaCl) and solvent composition (commercial and reagent-grade ethanol) were explored in detail. Through comprehensive parametric studies, we gained valuable insights into the influence of these variables on the size distribution of liposomes and succeeded in producing highly reproducible liposomes ranging from approximately 60 nm (corresponding to small unilamellar vesicles) to 150 nm (representing large unilamellar vesicles), all while maintaining a polydispersity index (PDI) of less than 0.2. To assess the encapsulation efficiency of hydrophobic drug molecules, Nile red (NR) was employed as a surrogate. We meticulously examined the impact of NR concentration on the drug encapsulation process, resulting in up to 74% drug encapsulation efficiency within the PEGylated liposomes. This research offers crucial advances in liposome synthesis and drug delivery, providing a high-throughput, controllable method for PEGylated liposomes with potential in pharmaceutical and biomedical fields.

PH-Sensitive Amphiphilic Diblock Polyphosphoesters with Lactate Units: Synthesis and Application as Drug Carriers.

pH-sensitive amphiphilic diblock polyphosphoesters containing lactic acid units were synthesized by multistep one-pot polycondensation reactions. They comprise acid-labile P(O)-O-C and C(O)-O-C bonds, the cleavage of which depends on the pH of the medium. The structure of these copolymers was characterized by 1H, 13C {H}, 31P NMR, and size exclusion chromatography (SEC). The newly synthesized polymers self-assembled into the micellar structure in an aqueous solution. The effects of the molecular weight of the copolymer and the length of the hydrophobic chain on micelle formation and stabilityand micelle size were studied via dynamic light scattering (DLS). Drug loading and encapsulation efficiency tests using doxorubicin revealed that hydrophobic drugs can be delivered by copolymers. It was established that the molecular weight of the copolymer, length of the hydrophobic chain and content of lactate units affects the size of the micelles, drug loading, and efficiency of encapsulation. A copolymer with 10.7% lactate content has drug loading (3.2 ± 0.3) and efficiency of encapsulation (57.4 ± 3.2), compared to the same copolymer with 41.8% lactate content (1.63%) and (45.8%), respectively. It was demonstrated that the poly[alkylpoly(ethylene glycol) phosphate-b-alkylpoly(ethylene glycol)lactate phosphate] DOX system has a pH-sensitive response capability in the result in which DOX was selectively accumulated into the tumor, where pH is acidic. The results obtained indicate that amphiphilic diblock polyphosphoesters have potential as drug carriers.

Preparation and sustained release of diatomite incorporated and Eudragit L100 coated hydroxypropyl cellulose/chitosan aerogel microspheres

The drug encapsulation efficiency, release rate and time, sustained release, and stimulus-response of carriers are very important for drug delivery. However, these always cannot obtained for the carrier with a single component. To improve the comprehensive performance of chitosan-based carriers for 5-Fu delivery, diatomite-incorporated hydroxypropyl cellulose/chitosan (DE/HPC/CS) composite aerogel microspheres were fabricated for the release of 5-fluorouracil (5-Fu), and the release performance was regulated with the content of diatomite, pH value, and external coating material. Firstly, the 5-Fu loaded DE/HPC/CS composite aerogel microspheres and Eudragit L100 coated microspheres were prepared with cross-linking followed by freeze-drying, and characterized by SEM, EDS, FTIR, XRD, DSC, TG, and swelling. The obtained aerogel microspheres have a diameter of about 0.5 mm, the weight percentage of F and Si elements on the surface are 0.55 % and 0.78 % respectively. The glass transition temperature increased from 179 °C to 181 °C and 185 °C with the incorporation of DE and coating of Eudragit, and the equilibrium swelling percentage of DE/HPC/CS (1.5:3:2) carriers are 101.52 %, 45.27 %, 67.32 % at pH 1.2, 5.0, 7.4, respectively. Then, the effect of DE content on the drug loading efficiency of DE/HPC/CS@5-Fu was investigated, with the increase of DE content, the highest encapsulation efficiency was 82.6 %. Finally, the release behavior of DE incorporated and Eudragit L100 Coated microspheres were investigated under different pH values, and evaluated with four kinetic models. The results revealed that the release rate of 5-Fu decreased with the increase of DE content, sustained release with extending time and pH-responsive were observed for the Eudragit-coated aerogel microspheres.

Redox-Responsive Gold Nanoparticles Coated with Hyaluronic Acid and Folic Acid for Application in Targeting Anticancer Therapy.

Methotrexate (MTX) has poor water solubility and low bioavailability, and cancer cells can become resistant to it, which limits its safe delivery to tumor sites and reduces its clinical efficacy. Herein, we developed novel redox-responsive hybrid nanoparticles (NPs) from hyaluronic acid (HA) and 3-mercaptopropionic acid (MPA)-coated gold NPs (gold@MPA NPs), which were further conjugated with folic acid (FA). The design of FA-HA-ss-gold NPs aimed at enhancing cellular uptake specifically in cancer cells using an active FA/HA dual targeting strategy for enhanced tumor eradication. MTX was successfully encapsulated into FA-HA-ss-gold NPs, with drug encapsulation efficiency (EE) as high as >98.7%. The physicochemical properties of the NPs were investigated in terms of size, surface charges, wavelength reflectance, and chemical bonds. MTX was released in a sustained manner in glutathione (GSH). The cellular uptake experiments showed effective uptake of FA-HA-ss-gold over HA-ss-gold NPs in the deep tumor. Moreover, the release studies provided strong evidence that FA-HA-ss-gold NPs serve as GSH-responsive carriers. In vitro, anti-tumor activity tests showed that FA-HA-ss-gold/MTX NPs exhibited significantly higher cytotoxic activity against both human cervical cancer (HeLa) cells and breast cancer (BT-20) cells compared to gold only and HA-ss-gold/MTX NPs while being safe for human embryonic kidney (HEK-293) cells. Therefore, this present study suggests that FA-HA-ss-gold NPs are promising active targeting hybrid nanocarriers that are stable, controllable, biocompatible, biodegradable, and with enhanced cancer cell targetability for the safe delivery of hydrophobic anticancer drugs.

Glutathione-Responsive and Hydrogen Sulfide Self-Generating Nanocages Based on Self-Weaving Technology To Optimize Cancer Immunotherapy.

As an ideal drug carrier, it should possess high drug loading and encapsulation efficiency and precise drug targeting release. Herein, we utilized a template-guided self-weaving technology of phase-separated silk fibroin (SF) in reverse microemulsion (RME) to fabricate a kind of hyaluronic acid (HA) coated SF nanocage (HA-gNCs) for drug delivery of cancer immunotherapy. Due to the hollow structure, HA-gNCs were capable of simultaneous encapsulation of the anti-inflammatory drug betamethasone phosphate (BetP) and the immune checkpoint blockade (ICB) agent PD-L1 antibody (αPD-L1) efficiently. Another point worth noting was that the thiocarbonate cross-linkers used to strengthen the SF shell of HA-gNCs could be quickly broken by overexpressed glutathione (GSH) to reach responsive drug release inside tumor tissues accompanied by hydrogen sulfide (H2S) production in one step. The synergistic effect of released BetP and generated H2S guaranteed chronological modulation of the immunosuppressive tumor microenvironment (ITME) to amplify the therapeutic effect of αPD-L1 for the growth, metastasis, and recurrence of tumors. This study highlighted the exceptional prospect of HA-gNCs as a self-assistance platform for cancer drug delivery.

Self-Signal-Triggered Drug Delivery System for Tumor Therapy Using Cancer Cell Membrane-Coated Biocompatible Mn3O4 Nanocomposites.

In anti-cancer metastasis treatment, precise drug delivery to cancer cells remains a challenge. Innovative nanocomposites are developed to tackle these issues effectively. The approach involves the creation of manganese oxide (Mn3O4) nanoparticles (NPs) and their functionalization using trisodium citrate to yield functionalized Mn3O4 NPs (F-Mn3O4 NPs), with enhanced water solubility, stability, and biocompatibility. Subsequently, the chemotherapeutic drug doxorubicin (DOX) is encapsulated with Mn3O4 NPs, resulting in DOX/Mn3O4 NPs. To achieve cell-specific targeting, These NPs are coated with HeLa cell membranes (HCM), forming HCM/DOX/Mn3O4. For further refinement, a transferrin (Tf) receptor is integrated with cracked HCM to create Tf-HCM/DOX/Mn3O4 nanocomposites (NC) with specific cell membrane targeting capabilities. The resulting Tf-HCM/DOX/Mn3O4 NC exhibits excellent drug encapsulation efficiency (97.5%) and displays triggered drug release when exposed to NIR laser irradiation in the tumor's environment (pH 5.0 and 6.5). Furthermore, these nanocomposites show resistance to macrophage uptake and demonstrate homotypic cancer cell targeting specificity, even in the presence of other tumor cells. In vitro toxicity tests show that Tf-HCM/DOX/Mn3O4 NC achieves significant anticancer activity against HeLa and BT20 cancer cells, with percentages of 76.46% and 71.36%, respectively. These results indicate the potential of Tf-HCM/DOX/Mn3O4 NC as an effective nanoplatform for chemo-photothermal therapy.

Kinetic and Mechanism of Zerumbone Release from Cross-linked Gelatin-Zeolite Y Hybrid for Oral Anticancer Drug Delivery

A hybrid of zeolite Y-gelatin film as an oral dosage form for the natural anticancer drug was achieved by homogenously incorporating the drug-loaded zeolite Y into the gelatin solution. Drug ability was analyzed using computational and experimental approaches, drug encapsulation efficiency via the BET method, and possible interactions by FTIR analyses. Zerumbone released was done in both pH 1.2 and pH 7.4 mimicking the human gastrointestinal tract conditions for 24 hrs and subjected to kinetics study via suitable mathematical models to determine what governs the drug release with the results indicating that a sustained delivery of once-daily oral dosage form could be achieved.