Facile Preparation of Paclitaxel Nano-Suspensions to Treat Lung Cancer

Lung cancer is a worldwide issue which account for the death of thousands every year. Paclitaxel (PTX) as the first line chemotherapy drug to treat lung cancer, its clinical applications is largely limited by its poor solubility. The facile preparation of pharmaceutical formulations to increase the solubility as well as targetability of PTX is of vital importance in lung cancer treatment. Herein, we introduced a facile method to prepare PTX nano-suspensions (NSs), which have high drug loading as well as well-dispersed particle size. The in vitro cell experiments revealed its capability to enhance the drug accumulation in A549 cells than free PTX. Moreover, in vivo animal assay suggested its better tumor accumulation and antitumor efficacy than PTX injection (Taxol).

Injectable Hydrogel as a Unique Platform for Antitumor Therapy Targeting Immunosuppressive Tumor Microenvironment

Cancer immunotherapy can boost the immune response of patients to eliminate tumor cells and suppress tumor metastasis and recurrence. However, immunotherapy resistance and the occurrence of severe immune-related adverse effects are clinical challenges that remain to be addressed. The tumor microenvironment plays a crucial role in the therapeutic efficacy of cancer immunotherapy. Injectable hydrogels have emerged as powerful drug delivery platforms offering good biocompatibility and biodegradability, minimal invasion, convenient synthesis, versatility, high drug-loading capacity, controlled drug release, and low toxicity. In this review, we summarize the application of injectable hydrogels as a unique platform for targeting the immunosuppressive tumor microenvironment.

Characterization of Drugs with Good Glass Formers in Loaded-Mesoporous Silica and Its Theoretical Value Relevance with Mesopores Surface and Pore-Filling Capacity

The incorporation of a drug into mesoporous silica (MPS) is a promising strategy to stabilize its amorphous form. However, the drug within MPS has shown incomplete release, despite a supersaturated solution being generated. This indicates the determination of maximum drug loading in MPS below what is experimentally necessary to maximize the drug doses in the system. Therefore, this study aimed to characterize the drugs with good glass former loaded-mesoporous silica, determine the maximum drug loading, and compare its theoretical value relevance to monolayer covering the mesoporous (MCM) surface, as well as pore-filling capacity (PFC). Solvent evaporation and melt methods were used to load each drug into MPS. In addition, the glass transition of ritonavir (RTV) and cyclosporine A (CYP), as well as the melting peak of indomethacin (IDM) and saccharin (SAC) in mesoporous silica, were not discovered in the modulated differential scanning calorimetry (MDSC) curve, demonstrating that each drug was successfully incorporated into the mesopores. The amorphization of RTV-loaded MPS (RTV/MPS), CYP-loaded MPS (CYP/MPS), and IDM-loaded MPS (IDM/MPS) were confirmed as a halo pattern in powder X-ray diffraction measurements and a single glass transition event in the MDSC curve. Additionally, the good glass formers, nanoconfinement effect of MPS and silica surface interaction contributed to the amorphization of RTV, CYP and IDM within MPS. Meanwhile, the crystallization of SAC was observed in SAC-loaded MPS (SAC/MPS) due to its weak silica surface interaction and high recrystallization tendency. The maximum loading amount of RTV/MPS was experimentally close to the theoretical amount of MCM, showing monomolecular adsorption of RTV on the silica surface. On the other hand, the maximum loading amount of CYP/MPS and IDM/MPS was experimentally lower than the theoretical amount of MCM due to the lack of surface interaction. However, neither CYP or IDM occupied the entire silica surface, even though some drugs were adsorbed on the MPS surface. Moreover, the maximum loading amount of SAC/MPS was experimentally close to the theoretical amount of PFC, suggesting the multilayers of SAC within the MPS. Therefore, this study demonstrates that the characterization of drugs within MPS, such as molecular size and interaction of drug-silica surface, affects the loading efficiency of drugs within MPS that influence its relevance with the theoretical value of drugs.

Design of a Controlled-Release Delivery Composite of Antibacterial Agent Gatifloxacin by Spherical Silica Nanocarrier

In this study, a spherical silica nanoparticle was explored as a gatifloxacin carrier synthesized by the chemical precipitation method. It was found that there was no new chemical bond formation during the loading process between gatifloxacin and silica, which implies that the binding was driven by physical interaction. In addition, the drug loading and encapsulation efficiency could be improved by appropriately increasing nano-silica content in the loading process. Meanwhile, the release rate of gatifloxacin after loading nano-silica was also improved, suggesting the successful design of a controlled-release delivery composite. The silica nanocarrier could significantly improve the antibacterial performance of Escherichia coli by 2.1 times, which was higher than the pure gatifloxacin. The 24 h bacteriostatic rate was higher than that of a simple mixture of silica nanoparticles and gatifloxacin. Strong reactive oxygen species (ROS) in GAT-SiO2 NPs suggests that ROS might be associated with bactericidal activity. The synergy between the physicochemical effect and ROS production of this material is proposed as the mechanism of its antibacterial activity, which can also be confirmed by the cell membrane damage observed under electron microscopy and DNA damage experiments. Collectively, our finding indicates that nano-silica microspheres could serve as a promising carrier for the sustained release of gatifloxacin, thereby providing a new carrier design scheme for the improvement of the antibacterial effect.

Synthesis and Characterization of Carboxymethyl Chitosan Nanosponges with Cyclodextrin Blends for Drug Solubility Improvement

This study aimed to enhance the solubility and release characteristics of docetaxel by synthesizing highly porous and stimuli responsive nanosponges, a nano-version of hydrogels with the additional qualities of both hydrogels and nano-systems. Nanosponges were prepared by the free radical polymerization technique and characterized by their solubilization efficiency, swelling studies, sol-gel studies, percentage entrapment efficiency, drug loading, FTIR, PXRD, TGA, DSC, SEM, zeta sizer and in vitro dissolution studies. In vivo toxicity study was conducted to assess the safety of the oral administration of prepared nanosponges. FTIR, TGA and DSC studies confirmed the successful grafting of components into the stable nano-polymeric network. A porous and sponge-like structure was visualized through SEM images. The particle size of the optimized formulation was observed in the range of 195 ± 3 nm. The fabricated nanosponges noticeably enhanced the drug loading and solubilization efficiency of docetaxel in aqueous media. The drug release of fabricated nanosponges was significantly higher at pH 6.8 as compared to pH 1.2 and 4.5. An acute oral toxicity study endorsed the safety of the system. Due to an efficient preparation technique, as well as its enhanced solubility, excellent physicochemical properties, improved dissolution and non-toxic nature, nanosponges could be an efficient and a promising approach for the oral delivery of poorly soluble drugs.

In vitro drug release and antibacterial activity evaluation of silk fibroin coated vancomycin hydrochloride loaded poly (lactic-co-glycolic acid) (PLGA) sustained release microspheres

Currently, the treatment of osteomyelitis poses a great challenge to clinical orthopedics. The use of biodegradable materials combined with antibiotics provides a completely new option for the treatment of osteomyelitis. In this study, vancomycin hydrochloride (VANCO) loaded poly (lactic-co-glycolic acid) (PLGA) microspheres were prepared by a double emulsion solvent evaporation method, and the in vitro drug release behaviors of the drug loaded microspheres were explored after coating with different concentrations of silk fibroin (SF). Drug loading, encapsulation efficiency, Scanning electron microscopy, particle size analysis, Fourier transform infrared spectroscopy, hydrophilicity, in vitro drug release, and in vitro antibacterial activity were evaluated. The results showed that the drug loading of vancomycin loaded PLGA microspheres was (24.11 ±1.72)%, and the encapsulation efficiency was (48.21 ±3.44)%. The in vitro drug release indicated that the drug loaded microspheres showed an obvious initial burst release, and the drug loaded microspheres coated with SF could alleviate the initial burst release in varying degrees. It also can reduce the amount of cumulative drug release, and the effect of microspheres coated with 0.1% concentration of SF is the best. The time of in vitro drug release in different groups of drug loaded microspheres can be up to 28 days. The microspheres coated with (0.1%SF) or without (0%SF) SF showed a cumulative release of (82.50±3.51)% and (67.70±3.81)%,respectively. Therefore, the surface coating with SF of vancomycin loaded microspheres can alleviate the initial burst release, reduce the cumulative drug release, potentially prolong the drug action time, and improve the anti-infection effect.

Enhanced Anti-Proliferative Effect of Carboplatin in Ovarian Cancer Cells Exploiting Chitosan – Poly (lactic glycolic acid) Nanoparticles.

Objective: The aim of the present article was to enhance the therapeutic efficacy of carboplatin (CP) using the formulation of chitosan – poly (lactic glycolic acid) nanoparticles (CS-PLGA NPs). Methods: Nanoparticles were synthesized by an ionic gelation method and were characterized for their morphology, particle size, and surface potential measurements by TEM and zeta sizer. This study was highlighted for the evaluation of drug entrapment, loading and in vitro drug release capabilities of the prepared nanoparticles by spectrophotometric analysis. The stability study was also conducted after 3 months for their particle size, zeta potential, drug loading and encapsulation efficiencies. Further, ovarian cancer cell line PEO1 were used to evaluate the toxicity and efficacy of nano-formulation by MTT assay. Further, the study was evaluated for apoptosis using flow cytometric analysis. Result: The CS-PLGA-CP NPs were uniform and spherical in shape. The particle size and zeta potential of CS-PLGA-CP NPs were measured 156 ± 6.8 nm and +52 ± 2.4 mV, respectively. High encapsulation (87.4 ± 4.5 %) and controlled retention capacities confirmed the efficiency of the prepared nanoparticles in a time and dose dependant manner. The cytotoxicity assay results also showed that CS-PLGA-CP NPs has high efficiency on PEO1 cells compared to the free drug. The flow cytometric result showed 64.25 % of the PEO1 cells were apoptotic and 8.42 % were necrotic when treated with CS-PLGA-CP NPs. Conclusion: Chitosan-PLGA combinational polymeric nanoparticles were not only steady but also non-toxic. Our experiments revealed that the chitosan- PLGA nanoparticles could be used as a challenging vehicle candidate for drug delivery for the therapeutic treatment of ovarian cancer.

Application of Nanoparticles in the Treatment of Lung Cancer With Emphasis on Receptors

Lung cancer is one of the malignant tumors that has seen the most rapid growth in terms of morbidity and mortality in recent years, posing the biggest threat to people’s health and lives. In recent years, the nano-drug loading system has made significant progress in the detection, diagnosis, and treatment of lung cancer. Nanomaterials are used to specifically target tumor tissue to minimize therapeutic adverse effects and increase bioavailability. It is achieved primarily through two mechanisms: passive targeting, which entails the use of enhanced penetration and retention (EPR) effect, and active targeting, which entails the loading recognition ligands for tumor marker molecules onto nanomaterials. However, it has been demonstrated that the EPR effect is effective in rodents but not in humans. Taking this into consideration, researchers paid significant attention to the active targeting nano-drug loading system. Additionally, it has been demonstrated to have a higher affinity and specificity for tumor cells. In this review, it describes the development of research into active targeted nano-drug delivery systems for lung cancer treatment from the receptors’ or targets’ perspective. We anticipate that this study will help biomedical researchers use nanoparticles (NPs) to treat lung cancer by providing more and novel drug delivery strategies or solid ligands.