Improved Drug Loading Research Articles

Polydopamine and hyaluronic acid immobilisation on vancomycin-loaded titanium nanotube for prophylaxis of implant infections

Titanium nanotube (Ti-NT) is an attractive substrate for local drug delivery, however, it is difficult to control the burst drug release and achieve sustained release from these nanotubes. In the present study, we investigated the feasibility of controlling drug release from Ti-NT within polydopamine and hyaluronic acid films, to achieve antibacterial activity and osteogenic promotion. Vancomycin was loaded into the Ti-NT by lyophilisation. Dopamine and hyaluronic acid were immobilized on the vancomycin-loaded Ti-NT surface through alternate deposition technique. The anti-infective and osteogenic abilities of the polydopamine and hyaluronic acid-modified Ti-NT were then investigated. Our results demonstrated that polydopamine and hyaluronic acid-modified Ti-NT exhibited improved drug loading and release control for 7 days. Compared with the vancomycin-loaded Ti-NT, the polydopamine and hyaluronic acid-modified Ti-NT exhibited better antibacterial ability, and the hyaluronic acid-modified Ti-NT promoted the osteogenic differentiation of rat bone marrow stem cells. Our results demonstrated that Ti-NT biofunctionalized with polydopamine and hyaluronic acid can help overcome the limitations of Ti-NT, by improving drug loading, antibacterial activity and osteogenic ability.

Exploiting hydrogen bonding to enhance lidocaine loading and stability in a poly ethylene-co-vinyl acetate carrier matrix

Sustained release of lidocaine from poly ethylene-co-vinyl acetate (EVA) implants can significantly improve pain management outcomes; however, poor drug loading is a major limitation. Recently, myristic acid was found to improve drug loading in EVA by inhibiting the crystallization of lidocaine. Here, lidocaine’s interaction with myristic acid was studied by differential scanning calorimetry. Spectra of lidocaine-myristic acid mixtures were analysed using two-dimensional correlation (2DCOS) maps. Furthermore, spectroscopic analysis of EVA matrices containing lidocaine, alone and in combination with myristic acid, was also performed and drug release was evaluated in vitro. A eutectic was obtained on combining lidocaine and myristic acid at the molar ratio of 1:1 due to loss of myristic acid’s dimeric conformation resulting in hydrogen bonding of its COOH group with lidocaine’s amide I moieties. In EVA, hydrogen bonding between adjacent lidocaine molecules caused crystallization above a threshold concentration and could be inhibited by incorporation of myristic acid by eutectic formation. By altering the molecular confirmation and solid state properties of lidocaine in EVA, myristic acid reduces lidocaine crystallization, increases drug loading and influences drug release kinetics. Exploiting these interactions and promoting further hydrogen bonding through the addition of specific excipients presents a viable strategy to enhance and stabilise drug loading in polymer matrices for various applications.

Polysaccharide-coated porous starch-based oral carrier for paclitaxel: Adsorption and sustained release in colon

A porous starch-based carrier coated with chitosan-phytic acid was designed for oral administration to improve drug delivery to the colon. Using hydrophobic paclitaxel as a model drug, improved drug loading (15.12% ± 0.31%) and entrapment efficiency (86.63 ± 1.30%) of porous starch were achieved by size/shape matching and adsorption force. Fluorescent paclitaxel particles inside starch were captured clearly. Furthermore, chitosan-phytic acid was added as a second protection since porous starch showed a dissolution rate of only 14.98–20.27% during the simulated digestion in stomach and small intestine, which was far lower than that of raw paclitaxel in porous starch (59.65 ± 2.57%). The release curve in the colon was also obtained and showed that 86.98 ± 2.90% of the drug was released. Finally, we verified the non-covalent interactions between starch and paclitaxel. This showed that the retention of paclitaxel into porous starch decreased once hydrogen bonding stopped. The hydrophobic CH-π effect provides a binding complementing contribution.

Hypoxia-Responsive Stereocomplex Polymeric Micelles with Improved Drug Loading Inhibit Breast Cancer Metastasis in an Orthotopic Murine Model.

Tumor metastasis is a leading cause of breast cancer-related death. Taxane-loaded polymeric formulations, such as Genexol PM and Nanoxel M using poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) micelles as drug carriers, have been approved for the treatment of metastatic breast cancer. Unfortunately, the physical instability of PEG-PLA micelles, leading to poor drug loading, premature drug leakage, and consequently limited drug delivery to tumors, largely hinders their therapeutic outcome. Inspired by the enantiomeric nature of PLA, this work developed stereocomplex PEG-PLA micelles through stereoselective interactions of enantiomeric PLA, which are further incorporated with a hypoxia-responsive moiety used as a hypoxia-cleavable linker of PEG and PLA, to maximize therapeutic outcomes. The results showed that the obtained micelles had high structural stability, showing improved drug loading for effective drug delivery to tumors as well as other tissues. Especially, they were capable of sensitively responding to the hypoxic tumor environment for drug release, reversing hypoxia-induced drug resistance and hypoxia-promoted cell migration for enhanced bioavailability under hypoxia. In vivo results further showed that the micelles, especially at a high dose, inhibited the growth of the primary tumor and improved tumor pathological conditions, consequently remarkably inhibiting its metastasis to the lungs and liver, while not causing any systemic toxicity. Hypoxia-responsive stereocomplex micelles thus emerge as a reliable drug delivery system to treat breast cancer metastasis.

Susceptibility of Lung Carcinoma Cells to Nanostructured Lipid Carrier of ARV-825, a BRD4 Degrading Proteolysis Targeting Chimera.

The present work was aimed at developing an optimized and modified nanostructured lipid carrier of BRD4 protein degrading Proteolysis Targeting Chimera (PROTAC) against non-small cell lung carcinoma. PROTACs are an emerging class of anticancer molecules with nanomolar activity but associated with significant solubility challenges. Lipid-based colloidal systems like nanostructured lipid carriers are widely explored for such highly lipophilic molecules. ARV-825, a cereblon-based PROTAC was investigated for its anticancer efficacy in vitro in 2D and 3D lung cancer models. ARV-825 loaded PEGylated nanostructured lipid carriers (AP-NLC) was prepared using melt emulsification technique. ARV-825 was stabilized using Precirol® ATO5 and Captex® 300 EP/NF as the solid and liquid lipid, respectively. However, hydrophobic ion-pairing with medium chain fatty acid was required to improve drug loading and stability. A hydrodynamic diameter and polydispersity index of 56.33 ± 0.42nm and 0.16 respectively with zeta potential of -21 ± 1.24mV was observed. In vitro migration and colony formation assay confirmed the anticancer activity of ARV-825 alone and AP-NLC. Nearly 38% and 50% apoptotic cell population were observed after ARV-825 and AP-NLC treatment. Immunoblotting assay showed complete suppression of BRD4 and c-Myc protein expression for AP-NLC. Most importantly, significant reduction in the growth of multicellular 3D spheroid of A549 cells confirmed the effectiveness of BRD4 PROTAC and its lipid nanoparticle in non-small cell lung cancer (NSCLC). AP-NLC. Higher amount of red fluorescence throughout the spheroid surface further confirmedsuperior efficacy of AP-NLC in tumor penetration and cell killing.

Injectable hydrogels with high drug loading through B–N coordination and ROS-triggered drug release for efficient treatment of chronic periodontitis in diabetic rats

The clinical management of chronic periodontitis with diabetes mellitus (CPDM) is a long-standing thorny issue. The excessive production of reactive oxygen species (ROS) is one of the important implications in CPDM. In the present study, oxidized dextran (OD) and phenylboronic acid-functionalized poly (ethylene imine) (PBA-PEI) were used to develop a novel injectable local drug delivery system (LDDS) which could simultaneously improve drug loading efficiency (doxycycline (Doxy) and metformin (Met)) through B–N coordination and achieve ROS-triggered drug release locally. The injectable LDDS exhibited appropriate adhesiveness to gingival tissue, good biocompatibility, and remarkable antibacterial effect against S. aureus, E. coli, and P. gingivalis. Furthermore, the favorable synergistic effect of Doxy and Met was also verified in vivo in a CPDM rat model through the morphometry and histological observations of alveolar bone, immunohistochemistry staining, and the detection of the expression level of immune-inflammatory mediators in gingival tissue. The results show that the double drug-loaded PBA-PEI/OD hydrogel, as a novel promising therapeutic agent, may be a favorable potential candidate for the CPDM management in the dental clinic.

Cytochalasin B Treatment and Osmotic Pressure Enhance the Production of Extracellular Vesicles (EVs) with Improved Drug Loading Capacity.

Extracellular vesicles (EVs) have been highlighted as novel drug carriers due to their unique structural properties and intrinsic features, including high stability, biocompatibility, and cell-targeting properties. Although many efforts have been made to harness these features to develop a clinically effective EV-based therapeutic system, the clinical translation of EV-based nano-drugs is hindered by their low yield and loading capacity. Herein, we present an engineering strategy that enables upscaled EV production with increased loading capacity through the secretion of EVs from cells via cytochalasin-B (CB) treatment and reduction of EV intravesicular contents through hypo-osmotic stimulation. CB (10 µg/mL) promotes cells to extrude EVs, producing ~three-fold more particles than through natural EV secretion. When CB is induced in hypotonic conditions (223 mOsm/kg), the produced EVs (hypo-CIMVs) exhibit ~68% less intravesicular protein, giving 3.4-fold enhanced drug loading capacity compared to naturally secreted EVs. By loading doxorubicin (DOX) into hypo-CIMVs, we found that hypo-CIMVs efficiently deliver their drug cargos to their target and induce up to ~1.5-fold more cell death than the free DOX. Thus, our EV engineering offers the potential for leveraging EVs as an effective drug delivery vehicle for cancer treatment.

Delivering more for less: nanosized, minimal-carrier and pharmacoactive drug delivery systems.

Traditional nanoparticle carriers such as liposomes, micelles, and polymeric vehicles improve drug delivery by protecting, stabilizing, and increasing the circulatory half-life of the encapsulated drugs. However, traditional drug delivery systems frequently suffer from poor drug loading and require an excess of carrier materials. This carrier material excess poses an additional systemic burden through accumulation, if not degradable the need for metabolism, and potential toxicity. To address these shortcomings, minimal-carrier nanoparticle systems and pharmacoactive carrier materials have been developed. Both solutions provide drug delivery systems in which the majority of the nanoparticle is pharmacologically active. While minimal-carrier and pharmacoactive drug delivery systems can improve drug loading, they can also suffer from poor stability. Here, we review minimal-carrier and pharmacoactive delivery systems, discuss ongoing challenges and outline opportunities to translate minimal-carrier and pharmacoactive drug delivery systems into the clinic.

Facile fabrication of hollow mesoporous bioactive glass spheres: From structural behaviour to in vitro biology evaluation

Bone defects accompanied by infection or inflammation can significantly delay the healing process. To simultaneously achieve controlled release of local antibiotics for infection control and bone healing, bone-implantable delivery systems have been considered as a promising strategy. This study aims to improve drug loading capacity of bone-implantable delivery systems by introducing hollow structure mesoporous bioactive glass nanospheres (HMBGs) through a sol–gel process. Particularly, such core–shell bimodal-porous structured nanoparticles were prepared through a sacrificing template using cetyltrimethylammonium bromide (CTAB) as surfactant. It was found that varying the amount of CTAB during the synthesis process is a simple and effective approach for tuning the particle size, morphology, and structure of HMBGs. For in vitro drug release, HMBGs could sustain storage and release of vancomycin hydrochloride (VAN) via diffusion-controlled mechanism, thereby inhibiting the bacteria growth in the subsequent bacterial study. Moreover, HMBGs incorporated with VAN provided a biomimetic microenvironment favored by cell adhesion and proliferation. These findings support the compatibility of HMBG nanoparticles with antibiotics and their potential application in the treatment of infectious bone defects.

Antibacterial and osteogenic activities of clindamycin-releasing mesoporous silica/carboxymethyl chitosan composite hydrogels.

Conventional treatment of jaw bone infection is often ineffective at controlling bacterial infection and enhancing bone regeneration. Biodegradable composite hydrogels comprised of carboxymethyl chitosan (CMCS) and clindamycin (CDM)-loaded mesoporous silica nanoparticles (MCM-41), possessing dual antibacterial activity and osteogenic potency, were developed in the present study. CDM was successfully loaded into both untreated and plasma-treated MCM-41 nanoparticles, denoted as (p)-MCM-41, followed by the incorporation of each of CDM-loaded (p)-MCM-41 into CMCS. The resulting CDM-loaded composite hydrogels, (p)-MCM-41-CDM-CMCS, demonstrated slow degradation rates (about 70% remaining weight after 14-day immersion), while the CDM-free composite hydrogel entirely disintegrated after 4-day immersion. The plasma treatment was found to improve drug loading capacity and slow down initial drug burst effect. The prolonged releases of CDM from both (p)-MCM-41-CDM-CMCS retained their antibacterial effect against Streptococcus sanguinis for at least 14 days in vitro. In vitro assessment of osteogenic activity showed that the CDM-incorporated composite hydrogel was cytocompatible to human mesenchymal stem cells (hMSCs) and induced hMSC mineralization via p38-dependent upregulated alkaline phosphatase activity. In conclusion, novel (p)-MCM-41-CDM-CMCS hydrogels with combined controlled release of CDM and osteogenic potency were successfully developed for the first time, suggesting their potential clinical benefit for treatment of intraoral bone infection.

Development of cefdinir loaded Functionalized carbon Nanotubes dry powder Inhaler for the Treatment of cystic Fibrosis

A dry-powder inhaler (DPI) carries medication to lungs as a dry powder, useful against respiratory diseases. The current research was endeavoured to examine the capabilities of Multi-walled carbon nanotubes (MWCNT) as a pulmonary transporter for directing cefdinir to cystic fibrosis (CF). Functionalized MWCNTs were loaded with cefdinir to formulate DPI (F-CEF FMWCNTs DPI) having efficient treatment against lung infections and were evaluated successfully. The outcomes demonstrated that cefdinir loaded FMWCNTs were non-toxic and accomplished 79.73 % entrapment with better flow properties. The optimized formulation had Mass Median Aerodynamic Diameter (MMAD), Fine particle fraction (FPF), and particle size of 3.45±0.09 μm, 58.52±1.06%, 5.25 ± 0.03 μm (CEF FMWCNT DPI) and 4. 29±0.16μm 38.74±1.02%, 7.54 ± 0.02 μm (C-DPI) respectively. The loaded nanotubes showed 72. 63 % release after 15 hours in a controlled manner. The outcome of work recognized a unique, simple, and stable product having improved drug loading and increased dispersibility of carbon nanotubes (CNTs) thus improved bioavailability at a lung infection place with less adverse actions.

Improvement of Drug-Loading Properties of Hydroxyapatite Particles Using Triethylamine as a Capping Agent: A Novel Approach

Particles that modify delivery characteristics are a focus of drug-loading research. Hydroxyapatite particles (HAPs) have excellent biocompatibility, shape controllability, and high adsorption, making them a potential candidate for drug-delivery carriers. However, there are still some defects in the current methods used to prepare HAPs. In order to avoid agglomeration and improve the drug-loading properties of HAPs, the present study provides a novel triethylamine (TEA)-capped coprecipitation template method to prepare HAPs at room temperature. In addition, pure water and anhydrous ethanol were used as solvents to investigate the capping effect of the small-molecule capping agent TEA during the synthesis of HAPs. The results showed that the HAPs prepared in the TEA ethanol system had a smaller particle size (150–250 nm), better dispersion and higher crystallinity. The results were significantly different from those of the conventional preparation methods without TEA. However, the hydroxyapatite crystal would agglomerate to a certain extent after being stored for a period of time, forming micro/nano-sized agglomerates of nanocrystals. FITR analysis and SEM observation showed that the capping effect of TEA promoted the formation of a smaller template and dispersed HAPs were quickly formed by dissolution and reprecipitation processes. The drug-loading experiments showed that the HAPs prepared in the TEA ethanol system had high drug-loading capacity (239.8 ± 13.4 mg·g−1) as well as an improved drug-release profile demonstrated in the drug-release experiment. The larger specific surface area associated with the smaller particle size was beneficial to the adsorption of drugs. After drying at 60 °C, TEA was evaporated from the HAPs which agglomerated into larger micron particles with more drug encapsulated. Thus, the effect of a sustained release was achieved. In the present research, a novel approach was developed by using triethylamine as the capping agent to prepare micro/nano-sized agglomerates of HAP nanocrystals with improved drug loading, which is predicted to have potential application in drug delivery.

Supramolecular nanofibers with superior anti-angiogenesis and antitumor properties by enzyme-instructed self-assembly (EISA)

Currently, combination therapy has become a popular research topic in cancer therapy. However, the outcome of the current combination therapy strategy does not satisfy the demand for clinical applications because of factors such as their overlapping toxicities, poor drug payload, and inevitable therapy resistance. Supramolecular self-assembly of peptides holds great potential for solving relevant problems and achieving superior therapeutic effects. In this study, we aimed to propose supramolecular self-assemblies based on a combination therapy strategy, consisting of a heptapeptide A7R for the inhibition of angiogenesis, the chemotherapeutic drug HCPT for treating numerous tumors with high efficacy, and an efficient self-assembling molecular FFY to improve drug loading and cell permeability. We regulated the secondary structure of nanomaterials by optimizing the pathways of self-assembly and significantly improved the affinity of A7R peptide to NRP-1. Endothelial tube formation in Matrigel and a tumor mouse model (in vivo) were then performed to demonstrate the superior antitumor effects of our supramolecular self-assemblies both in vitro and in vivo. In summary, this work not only provides a promising platform for the development of effective combination therapy, but also offers a useful strategy to prepare self-assembled nanomaterials with optimized performance.

A novel preparative method for nanoparticle albumin-bound paclitaxel with high drug loading and its evaluation both in vitro and in vivo

We developed a novel preparative method for nanoparticle albumin-bound (nab) paclitaxel with high drug loading, which was based on improved paclitaxel solubility in polyethylene glycol (PEG) and self-assembly of paclitaxel in PEG with albumin powders into nanoparticles. That is, paclitaxel and PEG were firstly dissolved in ethanol, which was subsequently evaporated under vacuum. The obtained liquid was then mixed with human serum albumin powders. Thereafter, the mixtures were added into phosphate-buffered saline and nab paclitaxel suspensions emerged after ultrasound. Nab paclitaxel was finally acquired after dialysis and freeze drying. The drug loading of about 15% (W/V) were realized in self-made nab paclitaxel, which was increased by approximately 50% compared to 10% (W/V) in Abraxane. Now this new preparative method has been authorized to obtain patent from China and Japan. The similar characteristics of self-made nab paclitaxel compared to Abraxane were observed in morphology, encapsulation efficiency, in vitro release, X-ray diffraction analysis, differential scanning calorimetry analysis, and circular dichroism spectra analysis. Consistent concentration-time curves in rats, biodistributions in mice, anti-tumor activities in mice, and histological transmutation in mice were also found between Abraxane and self-made nanoparticles. In a word, our novel preparative method for nab paclitaxel can significantly improve drug loading, obviously decrease product cost, and is considered to have potent practical value.

Co-delivery of glial cell-derived neurotrophic factor (GDNF) and tauroursodeoxycholic acid (TUDCA) from PLGA microspheres: potential combination therapy for retinal diseases.

Retinitis pigmentosa (RP) is a group of genetically diverse inherited disorders characterised by the progressive photoreceptors and pigment epithelial cell dysfunction leading to central vision impairment. Although important advances in the understanding of the pathophysiologic pathways involved in RP have been made, drug delivery for the treatment of ocular disorders affecting the posterior segment of the eye is still an unmet clinical need. In the present study, we describe the development of multi-loaded PLGA-microspheres (MSs) incorporating two neuroprotectants agents (glial cell-line-derived neurotrophic factor-GDNF and Tauroursodeoxycholic acid-TUDCA) as a potential therapeutic tool for the treatment of RP. A solid-in-oil-in-water (S/O/W) emulsion solvent extraction-evaporation technique was employed for MS preparation. A combination of PLGA and vitamin E was used to create the microcarriers. The morphology, particle size, encapsulation efficiency and in vitro release profile of the MSs were studied. Encapsulation efficiencies of GDNF and TUDCA for the initial multiloaded MSs, prepared with methylene chloride (MC) as organic solvent and polyvinyl alcohol (PVA) solution in the external phase, were 28.53±0.36% and 45.65±8.01% respectively. Different technological parameters to optimise the formulation such as the incorporation of a water-soluble co-solvent ethanol (EtOH) in the internal organic phase, as well as NaCl concentration, and viscosity using a viscosizing agent (hydroxypropyl methylcellulose-HPMC) in the external aqueous phase were considered. EtOH incorporation and external phase viscosity of the emulsion were critical attributes for improving drug loading of both compounds. In such a way, when using a methylene chloride/EtOH ratio 75:25 into the inner organic phase and the viscosity agent HPMC (1% w/v) in the external aqueous phase, GDNF and TUDCA payloads resulted 48.86±1.49% and 78.58±10.40% respectively, and a decrease in the initial release of GDNF was observed (22.03±1.41% compared with 40.86±6.66% of the initial multi-loaded formulation). These optimised microparticles exhibited sustained in vitro releases over 91 days. These results suggest that the microencapsulation procedure optimised in this work presents a promising technological strategy for the development of multi-loaded intraocular drug delivery systems (IODDS).

New approaches in extracellular vesicle engineering for improving the efficacy of anti-cancer therapies.

Cancer is a disease that evolves continuously with unpredictable outcomes. Although conventional chemotherapy can display significant antitumor effects, the lack of specificity and poor bioavailability remain major concerns in cancer therapy. Moreover, with the advent of novel anti-cancer gene therapies, there is an urgent need for drug delivery vectors capable of bypassing cellular barriers and efficiently transferring therapeutic cargo to recipient cells. A number of drug delivery systems have been proposed to overcome these limitations, but their successful clinical translation has been hampered by the onset of unexpected side effects and associated toxicities. The application of extracellular vesicles (EVs), a class of naturally released, cell-derived particles, as drug delivery vectors presents a breakthrough in nanomedicine, taking into account their biocompatibility and natural role in intercellular communication. Combining the advantageous intrinsic properties of EVs with surface functionalization and the encapsulation of drugs allows for a new class of engineered EVs that serve as effective therapeutic carriers. Here, we describe the various successful approaches involving the application of engineered EVs as bio-derived drug delivery vectors in cancer therapy. The latest and most effective strategies of engineering EVs to improve drug loading, stealth properties and tumour targeting capabilities of EVs are debated. Finally, current obstacles and future perspectives of smart engineered EVs are discussed.

Effect of XlogP and hansen solubility parameters on the prediction of small molecule modified docetaxel, doxorubicin and irinotecan conjugates forming stable nanoparticles

Small molecule-chemotherapeutic drug conjugate nanoparticles (SMCDC NPs) has a great advantage in improving drug loading. However, the factors which influence these conjugates forming stable nanoparticles (NPs) are currently unclear. In our previous studies, we synthesized a series of fatty acid-paclitaxel conjugates and suggested that the changes in the hydrophobic parameters (XlogP), solubility parameters and crystallinity of these fatty acid-paclitaxel conjugates were the key factors for affecting these small molecule-chemotherapeutic drug conjugates (SMCDCs) forming stable NPs in water. Here, we selected clinically widely used chemotherapeutic drug (docetaxel (DTX), doxorubicin (DOX) and irinotecan (Ir)) as model drug, and chose three straight-chain fatty acids (acetic acid (Ac), hexanoic acid (HA) and stearic acid (SA)) and one branched small molecule (N-(tert-butoxycarbonyl) glycine (B-G)) to synthesize 12 SMCDCs. Our results indicated that our prediction criterions obtained from paclitaxel conjugates were also appropriated for these synthesized SMCDCs. We suggested that the present studies expanded the scope of application of the above-mentioned influencing factors, provided research ideas for the rational design of SMCDC forming NPs and a basis for screening NPs with good anticancer activity.

Optimization, and in vitro and in vivo evaluation of etomidate intravenous lipid emulsion

The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties in vitro and in vivo. Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, −36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.

Conjugation of a smart polymer to doxorubicin through a pH-responsive bond for targeted drug delivery and improving drug loading on graphene oxide.

Polymeric nanoparticles have emerged as efficient carriers for anticancer drug delivery because they can improve the solubility of hydrophobic drugs and also can increase the bio-distribution of drugs throughout the bloodstream. In this work, a computational study is performed on a set of new pH-sensitive polymer–drug compounds based on an intelligent polymer called poly(β-malic acid) (PMLA). The molecular dynamics (MD) simulation is used to explore the adsorption and dynamic properties of PMLA–doxorubicin (PMLA–DOX) interaction with the graphene oxide (GOX) surface in acidic and neutral environments. The PMLA is bonded to DOX through an amide bond (PMLA-ami-DOX) and a hydrazone bond (PMLA-hz-DOX) and their adsorption behavior is compared with free DOX. Our results confirm that the polymer–drug prodrug shows unique properties. Analysis of the adsorption behavior reveals that this process is spontaneous and the most stable complex with a binding energy of −1210.262 kJ mol−1 is the GOX/PMLA-hz-DOX complex at normal pH. On the other hand, this system has a great sensitivity to pH so that in an acidic environment, its interaction with GOX became weaker while such behavior is not observed for the PMLA-ami-DOX complex. The results obtained from this study provide accurate information about the interaction of the polymer–drug compounds and nanocarriers at the atomic level, which can be useful in the design of smart drug delivery systems.

Covalent organic framework-engineered polydopamine nanoplatform for multimodal imaging-guided tumor photothermal-chemotherapy.

A covalent organic framework (COF)-engineered polydopamine core-shell nanoplatform (PDA@COF) was developed. The ultrasmall pores and abundant functional sites of the COF endowed the nanoplatform with enhanced drug loading capacity and diminished drug leakage effect. Multimodal imaging-guided photothermal chemo-synergistic tumor-targeted therapy was realized after rational functionalization. This work offers new insights for developing COF-based multifunctional theranostic systems.