Drug Loading Research Articles

Polymer homologue-mediated formation of hydrogel microneedles for controllable transdermal drug delivery

Poly(ethylene glycol) diacrylate (PEGDA) microneedles (MNs) are hydrogel-based devices that achieve controlled drug delivery kinetics by adjusting the crosslinking density. However, the biosafety of many crosslinking agents used to regulate crosslinking density is not ideal. To avoid crosslinking agents and simplify the preparation process, using two types of polymer homologues with different number-average molecular weights, we have successfully developed a series of PEGDA MNs with controllable crosslinking density (abbreviated as TP-X MNs). The research showed that the mechanical properties and drug release behavior of TP-X MNs could be tuned by simply controlling the weight proportion of two different PEGDA components in MNs. Ex vivo drug delivery experiments indicated that all TP-X MNs exhibited a sustained release profile, and their control range of 336-hour accumulative release rates was from 6.24% to 40.93%. Moreover, we prepared a novel dual-layer PEDGA MN, which can customize the drug loading and release rate in each layer of MN. This work demonstrates a new way to develop hydrogel MNs with adjustable crosslink density and broadens the applications of PEGDA MN in the biomedical field.

A Thin Polymer Layer Enables Peptide-Polycation Complexes with Ultrahigh Efficient Encapsulation.

A monolayer encapsulation is a new opportunity for engineering a system with high drug loading, but immobilizing polymer molecules on the surface of individual peptide nanoparticles is still an ongoing challenge. Herein, an individual peptide nanoparticle encapsulation strategy is proposed via surface adsorption, in which peptide molecules undergo granulation and subsequently aggregate with polymer molecules, forming a network via electrostatic interactions. Under the water phase, surplus polymer molecules dissolve, leading to a single nanoparticle encapsulation with a core-shell structure. As expected, the dense interfacial layer on the peptide nanoparticle surface achieves a superior loading degree of up to 95.4%. What's more, once the core-shell structure is established, the peptide mass fraction in individual encapsulation always exceeds 90% even under fierce external force. Following the individual nanoparticle encapsulation, the insulin-polycation complex (InsNp@PEI) reduces the inflammation from polymer and displays an effective glycemic control in type 1 diabetes. Overall, the newly developed single surface decoration encapsulates peptides with ultrahigh efficiency and opens up the possibility for further encapsulation.

Impact of dissolution medium pH and ionization state of the drug on the release performance of amorphous solid dispersions

Amorphous solid dispersions (ASDs) are widely employed as a strategy to improve oral bioavailability of poorly water soluble compounds. Typically, optimal dissolution performance from a polyvinylpyrrolidone vinyl acetate (PVPVA) based ASD is observed at relatively low drug loading limit. Above a certain drug load, termed limit of congruency (LoC), the release from ASDs significantly decreases. So far, the majority of the dissolution behavior has been tested in conditions where the drug primarily exists in unionized form. In this work, the impact of pH of the dissolution environment on the release performance of ASDs of an ionizable drug was studied. Atazanavir (ATZ), a weakly basic drug with a pKa of 4.5 was used as a model compound and PVPVA was used as a non-ionizable matrix polymer. Dissolution rate was measured using Wood's apparatus which normalizes the surface area of the dissolving tablet. The pH of the dissolution media was varied between 1 and 6.8, cover a range where ATZ exists as >99% ionized or unionized species. At pH 6.8, near complete release was observed only when the drug load was ≤ 6%. Unlike typically observed drastic decline in release behavior for PVPVA based ASDs above LoC, ATZ ASDs underwent gradual decline in dissolution behavior when the DL was increased to 8%. This was attributed to potential formation of an ATZ-PVPVA associated phase with dissolution rate slower than neat PVPVA. However, the 10% DL ASD showed negligible ATZ release. On another extreme (pH 1) where ATZ is ∼100% ionized, the dissolution rate of ATZ was faster than that of PVPVA. ASD dissolution rate was found to be slower than that of the neat drug but faster than PVPVA and interestingly, did not change with DL. This can be attributed to formation of an ionized ATZ-PVPVA phase which controls the dissolution rate of the ASD. At pH 3, where the drug is ∼97% ionized, near complete release was observed for drug loads ≤ 8%. To observe significant increase in drug loading with near complete release, >98% ionization of ATZ was required. At pH 2 where ATZ is ∼99.7% ionized, near complete release was observed for drug loads up to 30%. Furthermore, the deterioration in dissolution performance with an increase in drug load continued to be gradual at pH 2. The enhancement in dissolution performance did not correlate with solubility enhancement of ATZ due to ionization. We theorize that the enhancement in the dissolution performance due to ionization is the result of formation of an ionized ATZ-PVPVA phase which increases the hydrophilicity and the miscibility of the ASD. This can help resist water induced phase separation during ASD dissolution and therefore, result in continuous, and congruent dissolution of the drug and polymer.

Microscope-enabled Disc Dissolution System: Concordance between drug and polymer dissolution from an amorphous solid dispersion disc and visual disc degradation

A microscopic erosion time test was recently described to anticipate amorphous solid dispersion (ASD) drug load dispersibility limit, using 0.5ml media volume. Studies here build upon this microscope-enabled method but focus on drug and polymer dissolution from an ASD disc, along with imaging. The objective was 1) to design and build a microscope-enabled disc dissolution system (MeDDiS) with a 900mL dissolution volume and 2) assess the ability of MeDDiS imaging of dissolving discs to provide concordance with measured drug and polymer dissolution profiles. MeDDiS employed a digital microscope to image ASD discs and a one-liter vessel for dissolution. ASD discs containing ritonavir (5-50% drug load) and PVPVA were fabricated and subjected to in vitro dissolution using MeDDiS, where disc diameter was quantified with time. Ritonavir and PVPVA release were also measured. Results indicate concordance between imaging and dissolution. Both found 25% drug load to provide high drug and polymer release, but 30% yielded low release. Quantitatively, MeDDiS images predicted drug and polymer release profile, both above and below the drug load cliff. Overall, studies here describe a MeDDiS which has promised to anticipate drug and polymer dissolution, via imaging of dissolving discs, above and below the ASD drug load cliff.

Dysprosium-containing Cobalt Sulfide Nanoparticles as Anticancer Drug Carriers.

Among various materials designed for anticancer drug transport, sulfide nanoparticles are uniquely intriguing owing to their spectral characteristics. Exploration of newer nanoscale copper sulfide particles with dysprosium doping is reported herein. It leads to a change in the physicochemical properties of the sulfide nanoparticles and hence the difference in drug release and cytotoxicity. We intend to purport the suitably engineered cobalt sulfide and dysprosium-doped cobalt sulfide nanoparticles that are magnetic and NIR-absorbing, as drug delivery vehicles. The drug loading and release are based on the supramolecular drug complex formation on the surface of the nanoparticles. The nanomaterials are synthesized employing hydrothermal procedures, coated with a biocompatible poly-β-cyclodextrin, and characterized using the methods of diffractometry, microscopy, spectroscopy, thermogravimetry and magnetometry. The sustained drug release is investigated in vitro. 5-Fluorouracil is loaded in the nanocarriers. The empty and 5-fluorouracil-loaded nanocarriers are screened for their anti-breast cancer activity in vitro on MCF-7 cells. The size of the nanoparticles is below 10 nm. They show soft ferromagnetic characteristics. Further, they show broad NIR absorption bands extending up to 1200 nm, with the dysprosium-doped material displaying greater absorbance. The drug 5-fluorouracil is encapsulated in the nanocarriers and released sustainably, with the expulsion duration extending over 10 days. The IC50 of the blank and the drug-loaded cobalt sulfide are 16.24 ± 3.6 and 12.2 ± 2.6 μg mL-1, respectively. For the drug-loaded, dysprosium-doped nanocarrier, the IC50 value is 9.7 ± 0.3 μg mL-1. The ultrasmall nanoparticles possess a size suitable for drug delivery and are dispersed well in the aqueous medium. The release of the loaded 5-fluorouracil is slow and sustained. The anticancer activity of the drug-loaded nanocarrier shows an increase in efficacy, and the cytotoxicity is appreciable due to the controlled release. The nanocarriers show multi-functional characteristics, i.e., magnetic and NIR-absorbing, and are promising drug delivery agents.

Dissolution Mechanisms of Amorphous Solid Dispersions: Role of Polymer Molecular Weight and Identification of a New Failure Mode

The mechanisms of drug release from amorphous solid dispersions (ASDs) are complex and not fully explored, making it difficult to optimize for in vivo performance. A recurring behavior has been the limit of congruency (LoC), a drug loading above which the ASD surface forms an amorphous drug-rich barrier in the presence of water, which hinders release, especially in non-sink conditions. Drug-polymer interactions and drug glass transition temperature were reported to affect the LoC. However, the effect of polymer molecular weight has not been explored. ASDs of clotrimazole and different molecular weight grades of PVP were studied for their release to obtain their LoC drug loadings. Failure modes underpinning the LoC were investigated using fluorescence confocal microscopy to analyze the ASD/solution interface and phase behavior of ASD films at high relative humidity. ASDs with good release formed stable drug-rich nanodroplets at the ASD/solution interface, while ASDs with poor release were limited by one of two failure modes, depending on PVP molecular weight. In Failure Mode I the nanodroplets quickly agglomerated, while in Failure Mode II the system underwent phase inversion. This work highlights the importance of identifying the mechanisms underlying the LoC to improve the release of higher drug loading ASDs.

Curcumin-loaded lignin nanoparticles: Exploring sonication effects on drug loading and particle properties for future biomedical use

The present study investigates the effects of sonication and cross-linker (oxalic acid) concentration on drug loading and the properties of curcumin-loaded lignin nanoparticles. Selected samples were further assessed for their toxicity and antioxidant potential using the eukaryotic model organism Saccharomyces cerevisiae. Transmission electron microscopy analyses revealed the formation of spherical nanoparticles with diameters in the range of 39–49 nm. Differential scanning calorimetry experiments confirmed the encapsulation of curcumin. Factorial experimental design analyses indicated that sonication time, wave amplitude, cross-linker concentration, and their interactions significantly influenced both ζ-potential – from (−37.0 ± 1.7) mV to (−48.4 ± 0.6) mV – and curcumin loading – from (3.70 ± 0.32) % to (7.10 ± 0.57) %. These parameters are critical for biomedical applications as they relate to the clearance of nanoparticles from the human bloodstream and drug dosage optimization. Although sonication has been previously reported for the preparation of lignin nanoparticles, this study represents the first documented instance of manipulating drug loading by controlled sonication parameters. While none of the investigated factors significantly affected the mean particle diameter, observations from TEM micrographs suggest that cross-linker concentration and wave amplitude notably influence nanoparticle morphology. Moreover, the curcumin-loaded nanoparticles exhibited non-toxicity toward Saccharomyces cerevisiae and demonstrated the ability to enhance yeast cell tolerance to H2O2-induced oxidative stress, underscoring their antioxidant potential. Therefore, this research significantly contributes to the scientific understanding of how the control of sonication parameters and cross-linkers can modulate the properties of curcumin-loaded lignin nanoparticles for future biomedical applications.

Scale-up and clinical bioavailability assessment of a 45 % drug loaded amorphous nanoparticle formulation of a BCS IV compound for oral delivery

A 45 % drug loaded (DL) amorphous nanoparticle (ANP) formulation for a BCS IV drug demonstrated promising pharmacokinetics in dogs (Purohit, et al., J. Pharm. Sci. 2023(113)1007–1019). This preclinical data enabled a human proof-of-concept assessment opportunity. The ANP freeze dried powder for oral suspension was prepared using solvent/antisolvent precipitation followed by organic solvent removal and freeze drying (FD). Challenges manifested during scale-up from 50 g to 280 g. Given the preclinical data, formulation change was restricted, therefore, process modifications were implemented. Cold collection after precipitation prevented particle growth but resulted in 75 nm particles at clinical scale (CS), compared to 150 nm at laboratory scale (LS). This size decrease rendered stabilizer amounts suboptimal for FD operation. Consequently, when FD powder was resuspended in water a smaller fraction of particles was below 450 nm (by filtration), ∼65 % for CS compared to ∼85 % for LS. Formulation was stable for > 6 months, evaluated by monitoring moisture content, assay, powder X-ray diffraction (PXRD), and redispersion time. Despite ∼65 % re-dispersibility, this 45 % DL formulation in humans had higher Cmax and AUC ∼73 % and ∼46 % respectively in fasted-state, and under fed-state it met bioequivalence criteria for AUC but Cmax was 20 % lower compared to reference (10 % DL ASD tablets) demonstrating advantage of ANP strategy over ASD approach.

Bio-Inspired Nanodelivery Platform: Platelet Membrane-Cloaked Genistein Nanosystem for Targeted Lung Cancer Therapy.

Genistein (Gen), a natural polyphenolic compound, has emerged as a promising candidate for lung cancer treatment. However, the potential clinical application of Gen is limited due to its poor solubility, low bioavailability, and toxic side effects. To address these challenges, a biomimetic delivery platform with cell membranes derived from natural cells as carrier material was constructed. This innovative approach aims to facilitate targeted drug delivery and solve the problem of biocompatibility of synthetic materials. First, the liposomes (LPs) loaded with Gen (LPs@Gen) was prepared using the ethanol injection method. Subsequently, PLTM-LPs@Gen was obtained through co-extrusion after mixing platelet membrane (PLTM) and LPs@Gen. Additionally, the biological and physicochemical properties of PLTM-LPs@Gen were investigated. Finally, the targeting ability, therapeutic efficacy, and safety of PLTM-LPs@Gen for lung cancer were evaluated using both a cell model and a tumor-bearing nude mouse model. The optimal preparation ratio for LPs@Gen was Gen: soybean lecithin: cholesterol: DSPE-PEG2000 (3:30:5:10, mass ratio), while the ideal fusion ratio of LPs@Gen and PLTM was 1:1. The particle size of PLTM-LPs@Gen was 108.33 ± 1.06 nm, and the encapsulation efficiency and drug loading were 94.29% and 3.09% respectively. Gen was released continuously and slowly from PLTM-LPs@Gen. Moreover, PLTM-LPs@Gen exhibited good stability within one week. The results of in vitro cellular uptake and in vivo distribution experiments indicated that the carrier material, PLTM-LPs, has the immune escape ability and tumor targeting ability. Consequently, it showed better therapeutic effects than free drugs and traditional LPs in vitro and in vivo tumor models. In addition, safety experiments demonstrated that PLTM-LPs@Gen possesses good biocompatibility. Biomimetic nanomedicine provides a new strategy for the precision treatment of lung cancer in clinical practice.

Coupling simulation and experimental study of drug loading and releasing behaviors in phytol-based micelles

Phytol, as a potential drug-carrier, can regulate the cellular reactive oxygen species (ROS) levels in a dose-dependent manner, decreasing them at lower doses and increasing them at higher doses. In this study, we developed phytol-based micelles composed of phytol, PEG, and OE, which can clearly enhance drug delivery efficacy and simultaneously protect normal cells. Drug-loading and -releasing mechanisms of phytol-based micelles were investigated combined with dissipative particle dynamics (DPD) simulations and experimental. The simulation results indicate that Ph4EO22Ph4 exhibits the most desirable properties for forming phytol-based micelles compared with other phytol-based polymers we designed. We found that co-loading (purpurin 18 a) P18 and paclitaxel (PTX) within the Ph4EO22Ph4 micelle not only enhances the encapsulation efficiency (EE) of P18 (P18’s EE rised from 85.16 % to 91.17 %) but also optimizes the overall micellar structure, exhibiting excellent DL capability along with sustained release (75.2 % PTX releasing after 72 h) performance under acidic conditions. The release mechanism varies with the loaded drugs, in which PTX is released in its molecular form while P18 is released through P18/Ph4 particles. In the latter case, Ph4 within the particles significantly facilitates cellular uptake of P18 drugs by 4T1 cells, thereby enhancing therapeutic efficacy. Interestingly, Ph4EO22Ph4 exhibited significantly higher cytotoxicity towards 4T1 cells compared to HC11. Therefore, the phytol-based micelles incorporating a concentration-dependent hydrophobic block and a steric effect-driven hydrophilic block composed of PEG demonstrated enhanced efficacy and reduced toxicity. The present study presents a novel phytol-based micelle system incorporating DPD simulation and experimental validation, which effectively addresses the challenges encountered by P18 and PTX. Moreover, it comprehensively investigates drug loading and releasing behaviors in phytol-based micelles from various perspectives, thereby offering valuable insights for the design of alternative drug delivery systems.

Development and evaluation of novel taste-masking tilmicosin microcapsules containing octenylsuccinic anhydride modified starch and maltodextrin as wall materials

Tilmicosin (TMS) is an important antibiotic in veterinary medicine, but its extreme bitter taste limits its use. In this study, TMS was encapsulated in octenyl succinic anhydride modified starch/maltodextrin (HI-CAP/MD) composite capsules with a spray drying method. The TMS microcapsules (TMS-MC) exhibited good drug loading performance with drug loading (DL) and encapsulation efficiency (EE) of 9.90 ± 0.23 % and 98.03 ± 1.56 %, respectively. There was no significant change in particle diameter and zeta potential for the emulsion and redissolved TMS-MC. These results combined with FT-IR, TGA and DSC showed the crystalline shape and chemical structure of TMS did not change during the microencapsulation. In vitro release characterization in an acidic medium (pH 1.2) and an alkaline medium (phosphate buffered solution, pH 6.8) showed that TMS-MC can be rapidly released in vitro. The bitterness evaluation implied the bitterness of TMS was masked after microencapsulation. In vitro bacterial inhibition test showed the bacterial inhibitory activity of TMS was not reduced by the microencapsulation, but was much better than that of the commercially available tylosin (TLS). Therefore, HI-CAP/MD can effectively encapsulate TMS, mask the bitter taste and maintain a good bacterial inhibitory effect, making a new drug formulation with good development prospects.

Dissolution, phase behavior and mass transport of amorphous solid dispersions in aspirated human intestinal fluids

Amorphous solid dispersions (ASDs) typically show improved dissolution and generate supersaturated solutions, enhancing the oral bioavailability of poorly soluble drugs. To gain insights into intraluminal ASD behavior, we utilized two poorly soluble drugs with different crystallization tendencies, atazanavir and posaconazole, prepared as ASDs at a 10% drug loading with hydroxypropyl methylcellulose acetyl succinate (HPMCAS). We evaluated their release in aspirated fasted-state human intestinal fluid (FaHIF), and multi-component fasted-state simulated intestinal fluid (composite-FaSSIF), characterizing the supersaturation profiles and drug-rich nanodroplets that formed. Complete release was observed for atazanavir ASDs over a 90 min period. Flux for dissolved atazanavir ASDs remained high over the experimental time period of 3 h. In contrast, posaconazole solution concentrations were initially high and then decreased. Likewise, flux was initially high and then decreased where these changes are attributed to crystallization of the drug. Generation of spherical nano-sized amorphous droplets of ∼100-150 nm was found to occur in ex vivo FaHIF media for both ASDs, maximizing the diffusive flux during the supersaturation window. Moreover, buffer capacity differences were postulated to influence release rates of ASDs in simulated vs aspirated fluids. Importantly, the solution phase phenomena observed during ASD release in simulated fluids, namely amorphous nanodroplet formation and drug crystallization, were also found to occur in aspirated luminal fluids.

Synthesis and in vitro study of surface-modified and anti-EGFR DNA aptamer -conjugated chitosan nanoparticles as a potential targeted drug delivery system

Nowadays, finding effective approaches for cancer therapy is one of the significant issues related to human health all over the world. Hence, in this research, we designed and synthesized a novel targeted DDS based on surface-modified chitosan (CS) for the effective delivery of noscapine (NO). As the surface of CS nanoparticles was firstly modified with carboxyl groups and followed by covalent conjugation of DNA-aptamer (Ap) as targeting and receptor blocker agent. Secondly, NO, as a chemotherapeutic agent, was loaded into prepared nano-complex and synthetics were effectively characterized via various analytical devices, including FT-IR, 1H NMR, DLS, Zeta potential analyzer, TGA, TEM, and SEM to verify quality and quantity of synthetics. Drug loading was obtained about 25 % and sustained drug release was observed for nano-complex at different pHs. Then, the cell viability assay was performed on MCF-7 (as breast cancer cell) and HFF-1 (as normal cell) cell lines to investigate cancer cell inhibition potency of nano-complex. Cell viability of cancer cells was 19.84 ± 1.87 % (for C-CS-Ap-NO) and 75.43 ± 2.64 % (for C-CS-Ap) after 72 h of treatment with 400 nM concentration. These results have been confirming the excellent potency of synthesized novel nano-complex as practical DDS in cancer therapy.

Chitosan-melanin complex microsphere: A potential colonic delivery system for protein drugs

The characteristics and performance of chitosan-based colon delivery systems are significantly influenced by the method of preparation. Insect chitosan-melanin complex (CMC) may offer superior attributes over traditional shrimp and crab chitosan (CS) for colon-targeted administration. This study used dung beetle CMC as the carrier matrix and comprehensively examined the impact of various crosslinking techniques on the colonic drug delivery efficacy of microspheres, encompassing drug loading, swelling, drug release behavior, adhesion, enzymatic degradation, and absorption enhancement. The results indicate that F-TPPLC microspheres, crosslinked with a combination of formaldehyde and TPP, exhibit superior drug loading capabilities, optimal swelling behavior, and controlled in vitro drug release profiles in the colonic environment, along with excellent adhesion and enzymatic degradation properties within intestinal tract. Notably, these F-TPPLC microspheres increase paracellular permeability, possibly by disrupting the calcium-dependent adhesion junctions. In comparison to commercial CS, CMC demonstrates superior drug encapsulation efficiency, enhanced colonic drug release, adhesion, and absorption promotion, rendering it a favorable candidate as a carrier in colon-targeted drug delivery systems. Consequently, F-TPPLC microspheres derived from CMC are highly suitable for colon drug delivery applications and show promising potential for the oral delivery of peptide and protein-based therapeutics to the colon.

Development, Optimization, and Characterization of Polymeric Micelles to Improve Dasatinib Oral Bioavailability: Hep G2 Cell Cytotoxicity and In Vivo Pharmacokinetics for Targeted Liver Cancer Therapy

The efficacy of dasatinib (DAS) in treating hepatocellular carcinoma (HCC) is hindered by its poor bioavailability, limiting its clinical potential. In this study, we explored the use of TPGS-Soluplus micelles as an innovative drug delivery platform to enhance DAS solubility, stability, and therapeutic impact. A series of TPGS-Soluplus copolymers were synthesized, varying the D-α-tocopheryl polyethylene glycol succinate (TPGS) forms (1000, 2000, and 3500) and adjusting the TPGS to Soluplus weight ratios (1:1, 1:2, and 1:3). Our goal was to identify the optimal formulation with the highest entrapment efficiency, smallest particle size, and enhanced drug loading. The TPGS1000-Soluplus copolymer, with a DAS-to-polymer ratio of 1:30 and a TPGS ratio of 1:2, demonstrated superior performance, achieving an entrapment efficiency of 64.479 ± 1.45% and drug loading of 5.05 ± 1.01%. The DAS-loaded micelles (DAS-PMs) exhibited a notably small particle size of 64.479 ± 1.45 nm and demonstrated controlled release kinetics, with 85.60 ± 5.4% of the drug released over 72 hours.Cellular uptake studies using Hep G2 cells revealed significantly enhanced absorption of DAS-PMs compared to free DAS, reflected in lower IC50 values in MTT assays at 24 and 48 hours. Pharmacokinetic analysis further highlighted the benefits of the DAS-PMs, with an AUC0-∞ 2.16 times higher and mean residual time (MRT) 1.3 times longer than free DAS, a statistically significant improvement (p < 0.01). These findings suggest that TPGS-Soluplus micelles offer a promising strategy for improving the bioavailability and efficacy of DAS in HCC treatment, presenting a potential new therapeutic avenue for patients with limited options. This innovative formulation could significantly enhance DAS delivery, potentially leading to improved clinical outcomes in liver cancer therapy.

Preparation, Swelling, and Drug Release Studies of Chitosan-based Hydrogels for Controlled Delivery of Buspirone Hydrochloride.

Buspirone is used for the management of depression and anxiety disorders. Due to its short half-life and low bioavailability, it requires multiple daily doses and is associated with some side effects. This study aimed to develop chitosan-based hydrogels as drug-controlled release carriers. The objective of this study is to prepare chitosan-based hydrogels as controlled release carriers in order to overcome the side effects of buspirone HCl and improve patients' compliance and their life quality. Polymer chitosan was polymerized with two monomers, acrylic acid and itaconic acid, to synthesize pH-sensitive hydrogel. The Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis were performed to confirm the structure formation and thermal stability. Water penetration capability and loading of the drug were performed by porosity and drug loading studies. The swelling and dissolution tests were performed to analyze the pH-sensitive nature of the developed hydrogels. FTIR, TGA, and DSC demonstrated that the chitosan-based hydrogels were successfully prepared. An increase in water penetration and drug loading into the hydrogel network was seen with the high incorporation of chitosan, acrylic acid, and itaconic acid. The swelling and dissolution studies revealed that prepared hydrogel offered the greatest swelling and drug release at a high pH of 7.4. The swelling and drug release from the hydrogel were affected by the concentrations of the incorporated contents. A controlled release of the drug was achieved by using chitosan-based hydrogel as a delivery carrier compared to commercial tablets of buspirone. The results showed that the developed chitosan-based hydrogel can be considered one of the most suitable drug carrier systems for the controlled delivery of buspirone.

Design and development of DSPE-PEG2000/DPPC disk-like micelles for targeted delivery of icariin phytochemical in pulmonary fibrosis

Icariin (ICA)-loaded DSPE-PEG2000/DPPC disk-like micelles were synthesized utilizing the thin film hydration method to enhance the solubility and delivery of ICA to the lungs. The micellar formulation significantly improved the water solubility of ICA. This was attributed to the high encapsulation efficiency (95 %) and drug loading capacity (12 %) of the DSPE-PEG2000/DPPC micelles. Comprehensive characterization using Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Particle size analysis through dynamic light scattering (DLS) and transmission electron microscopy (TEM) demonstrated the formation of stable micelles with an average particle size around 10 nm.In vitro aerosolization studies using the next-generation impactor (NGI) revealed that the fine particle fraction was 63.5 ± 4 %, which means that over 60 % of the aerosolized ICA/DSPE-PEG2000/DPPC micelles were capable of reaching and targeting the deep lung alveoli, indicating their potential efficacy for pulmonary delivery. Cytotoxicity assessments via the MTT assay showed IC50 values of ICA-loaded DSPE-PEG2000/DPPC micelles were 117 ± 8 μg/mL, 29 ± 3 μg/mL, and 21 ± 1 μg/mL at 24, 48, and 72 h, respectively, highlighting the time-dependent cytotoxic effects of the ICA-loaded micelles on A549 cells. However, the IC50 values of free ICA were > 500 μg/mL, 252 ± 3 μg/mL, and 109 ± 2 μg/mL, respectively at three different time points. That indicated that ICA-loaded nano micelles enhanced the cytotoxicity of ICA. Furthermore, the cellular uptake of the nano micelles by A549 cells was visualized and confirmed using EVOS fluorescence imaging and flow cytometry techniques. In addition, RAW 264.7 M2 polarization studies indicated ICA loaded DSPE-PEG2000/DPPC micelles have potential for treating pulmonary fibrosis.These findings suggest that DSPE-PEG2000/DPPC micelles significantly enhance the solubility and delivery of ICA, presenting a promising nanocarrier system for targeted pulmonary fibrosis therapy.

Research Progress on Immunomodulatory Effects of Poly (Lactic-co- Glycolic Acid) Nanoparticles Loaded with Traditional Chinese Medicine Monomers.

Immunomodulatory mechanisms are indispensable and key factors in maintaining the balance of the environment in humans. When the immune function of the immune system is impaired, autoimmune diseases occur. Excessive body fatigue, natural aging of the human body, malnutrition, genetic factors and other reasons cause low immune function, due to which the body is prone to being infected by bacteria or cancer. Clinically, the existing therapeutic drugs still have problems such as high toxicity, long treatment cycle, drug resistance and high price, so we still need to explore and develop a high efficiency and low toxicity drug. Poly(lactic-co-glycolic acid) (PLGA) refers to a nontoxic polymer compound that exhibits excellent biocompatibility. Traditional Chinese medicine (TCM) monomers come from natural plants, and have the characteristics of high efficiency and low toxicity. Applying PLGA to TCM monomers can make up for the defects of traditional dosage forms, improve bioavailability, reduce the frequency and dosage of drug use, and reduce toxicity and side effects, thus having the characteristics of sustained release and targeting. Accordingly, PLGA nanoparticles loaded with TCM monomers have been the focus of development. The previous research on drug loading advantages, preparation methods, and immune regulation of TCM PLGA nanoparticles is summarized in the following sections.

Targeted delivery of quercetin using gelatin/starch/Fe3O4 nanocarrier to suppress the growth of liver cancer HepG2 cells

To suppress HepG2 liver cancer cells, a nanocarrier (NC) consisting of Fe3O4, Gelatin (G), and Starch (S) was synthesized and characterized for targeted delivery of Quercetin (QC) drug. The spectra obtained from X-ray diffraction (XRD) and Fourier transform infrared (FTIR) demonstrated that the nanoparticles (NP) in the NC are well-interconnected to each other and have formed a regular structure. Also, field emission scanning electron microscopy (FE-SEM) indicates a smooth and homogeneous surface of the synthesized NC. The results of the vibrating sample magnetometer (VSM) also corroborated the correctness of the synthesis of Fe3O4 NPs and Gelatin/Starch/Fe3O4@Quercetin NC (G/S/Fe3O4@QC) because the magnetic properties of Fe3O4 decreased with the addition of G/S@QC. Stability and particle size were determined by zeta potential and Dynamic light scattering (DLS). The percentage of drug loading and encapsulation efficiency of QC in the NC was 46.25 % and 87 %, respectively. QC profile release in acidic and natural environments showed controlled release and pH sensitivity of the NC. Cytotoxicity of L929 and HepG2 treated cells with the G/S/Fe3O4@QC was investigated by MTT staining, which agreed with the flow cytometry result. The results of Flowcytometry and MTT showed 43.5 % apoptosis and 42 % cytotoxicity in treated HepG2 cells by G/S/Fe3O4@QC, while it was not toxic to L929 normal cells. According to the results, G/S/Fe3O4@QC is a suitable NC for the targeted delivery of QC as a drug against HepG2 cancer cells.

Polypeptide-Based Copper Ionophore for In Situ Glutathione-Triggered Chemodynamic and Chemotherapy.

Intracellular copper ion homeostasis has become an attractive target for cancer therapy. Herein, we report a 2,2'-dipicolylamine (DPA) functionalized polyglutamate derivative (PDHB) which is capable of rapidly forming PDHB-copper complex (PDHB@Cu) due to the strong coordination ability of pendant DPA with Cu2+. High drug loading content of doxorubicin (DOX) (>30 wt %) is realized due to the strong affinity of Cu2+ to DOX, while that is about 10 wt % for PDHB without Cu2+. The obtained PDHB@Cu-DOX can respond to specific endogenous stimuli (pH and glutathione (GSH)), releasing Cu2+ and DOX. The released DOX directly damages the DNA of tumor cells to cause apoptosis, while Cu2+ depletes intracellular GSH and is reduced to Cu+ simultaneously, which reacts with local H2O2 to produce highly toxic ·OH via a Fenton-like reaction, thus realizing synergistic chemodynamics and chemotherapy. This report provides an interesting polymeric ionophore strategy to deliver enough copper ions into cancer cells, which can also easily extend to other metal ions by replacing the ionophore components, thus having a wide application in nanomedicine.