EGFR Targeted Nanocarriers for Cancer Diagnosis and Therapy

Conventional cancer management is directly associated with many problems, including accurate therapeutic delivery to tumours and serious side effects of chemotherapeutics. A specific and efficient anticancer delivery to the tumour site without damaging normal tissues is the ultimate goal of all cancer treatment strategies. Nanomedicine has immense potential for cancer therapy that focuses on improving treatment efficacy, while reducing toxicity to normal tissues as well. However, the biodistribution and targeting capability of nanoparticles lacking targeting ligands rely solely on their physicochemical properties and the pathophysiological parameters of the body. Targeting is a promising strategy for selective and efficient therapeutic delivery to tumour cells with reduced detrimental side effects. Taking advantage of the fact that molecular markers and receptors over-express on the tumour cell surface as compared to a normal cell, the active targeting approach would be beneficial for cancer therapy. The epidermal growth factor receptors (EGFR), abnormally overexpressed in many epithelial tumours, have received much attention for molecular targeting in cancer diagnostics and therapeutics. This review presents the role of EGFR targeting in cancer imaging and therapy, and some recent researches on treatment of EGFR overexpressing cancers by using targeted nanoparticulate platforms. It also discusses illustrative examples of various ligands, including antibodies, antibody fragments, nanobodies, and peptides.HighlightsHighlights the potential of EGFR targeted nanocarriers for cancer diagnosis and therapy.Summarizes the role of EGFR targeting in cancer therapy.Describes various examples of recent researches on EGFR targeted nanocarriers.Explains illustrative examples of various ligands for EGFR targeting.

Preparation and Optimization of Vancomycin hydrochloride Encapsulated Multivesicular Liposomes for Sustained Locoregional Delivery

Introduction: Osteomyelitis is a destructive inflammatory condition of the bone that is usually caused by a wide range of microorganisms especially Staphylococcus aureus. Considering the downsides of systemic antibiotic therapies as well as conventional local drug delivery systems such as using polymethylmethacrylate, this study aimed to develop, characterize and optimize vancomycin hydrochloride loaded multivesicular liposomes (MVLs) as a proper therapeutic option for the treatment of osteomyelitis. Methods and Results: A 23 full factorial design technique was applied to determine the effects of three variables (lipid to drug ratio, triolein content and cholesterol to phospholipid ratio) on the encapsulation efficiency and release profile of vancomycin hydrochloride loaded MVLs to optimize the final formulation. Further characterization was performed on the optimized formula by evaluating the morphology, size and storage stability. The average drug encapsulation efficiency and the mean diameter of the optimized formulation was 54.7 ± 0.3% and 9.019 ± 0.26 µm, respectively with a span value of 0.188. Additionally, the spherical and multivesicular nature of MVLs was visible using optical microscopy (x400). The optimized formula showed an in vitro sustained release characteristic with proper stability and insignificant change in size, morphology and EE% for 30 days at 4°C. Conclusion: This study suggests that vancomycin hydrochloride loaded MVLs might have the potential to be used in the treatment of chronic osteomyelitis as a biocompatible drug carrier with a high antibiotic entrapment capacity as well as controlled drug release

Tacrolimus phospholipid based nanomicelles as a potential local delivery system for corneal neovascularization therapy

Introduction: Tacrolimus, an immunosuppressive agent, has been shown to be an effective treatment against corneal neovascularization (CNV). However, the poor solubility of this compound restricts its clinical application. The goal of this study was to incorporate tacrolimus into phospholipid-bile salt mixed micelles. Methods and Results: Tacrolimus loaded phospholipid-bile salt mixed micelles were prepared, employing three different methods of direct dispersion, thin film hydration, and remote film loading, and the effects of various formulation parameters (type of dispersion medium, phospholipid to bile salt molar ratio, lipid-to-drug (L/D) molar ratio, time of probe sonication, and type of bile salt) on the physicochemical characteristics of the mixed micelles were assessed. Remote film loading method indicated higher efficacy for drug entrapment in comparison to the other methods. Encapsulation of tacrolimus within the micelles increased remarkably by the use of sodium taurocholate (NaTC) as bile salt, higher phospholipid percentage, and increasing the total lipid level. Atomic force microscopy (AFM) studies confirmed the size and size distribution of the mixed micelles and their spherical morphology. It was observed that release of tacrolimus from the micelles was in a controlled manner, without an initial burst. Conclusions: By adjusting process and formulation factors, phospholipid-bile salt mixed micelles with high entrapment efficiency of (99.5 %) and controlled release behavior were achieved, which possess great potential to be valuable carriers for ocular delivery of tacrolimus for the treatment of CNV.                                                                                                                                       &nbsp

Preparation and In Vitro Characterization of Crocin-loaded Casein Hydrogels: Crocin-loaded casein hydrogels

Crocin, the main active constituent of saffron, has many important biological activities. Due to its anti-inflammatory properties, crocin can be potentially effective in different pathological conditions including oral ulcers. Novel drug delivery systems such as hydrogels have been used to increase the stability of crocin and provide a controlled release of this compound. Casein is the main protein of milk that possesses suitable properties for the fabrication of hydrogels. In this paper, casein-based hydrogels with different casein to crocin weight ratios were synthesized using the acid-gelation method. The prepared crocin-loaded hydrogels were characterized regarding their rheological behavior, drug content, swelling ratio, surface morphology, thermal stability, and in vitro release profile. The structure of casein hydrogels was characterized using Fourier transform infrared and X-ray diffraction. All formulations exhibited a pseudoplastic rheological behavior and there was no statistically significant difference in viscosity among them. Hydrogel with casein to crocin weight ratio of 10:1 had larger pores and demonstrated a higher swelling percentage and suitable thermal stability. All casein-based hydrogels demonstrated a slow release of crocin over 24 hours and the hydrogel with lower casein to crocin weight ratio had an increased release rate. Taken together, casein-based hydrogels were found to be effective carriers to provide a controlled release system for crocin delivery. HIGHLIGHTS Casein-based hydrogels were developed for delivery of crocin. Casein-based hydrogels provided a controlled in vitro release profile for crocin. Hydrogel with a lower casein ratio exhibited a higher release rate of crocin

Quercetin nanocrystals prepared by a novel technique improve dissolution rate and antifibrotic activity of quercetin - Supplementary materials

Aim: To develop quercetin nanocrystals by a simple approach and to evaluate their in vivo antifibrotic efficacy. Materials & methods: Nanosuspensions were fabricated by a thin-film hydration technique and ultrasonication. The influence of process variables on the average diameter of quercetin nanoparticles was investigated. Moreover, in vivo efficacy was investigated in an established murine CCl4-induced fibrosis model. Results: Nanocrystals showed a particle size of increase in dissolution rate and solubility. Quercetin nanocrystals markedly prevented fibrotic changes in the liver, as evidenced by mitigated histopathological changes and diminished aminotransferase levels and collagen accumulation. Conclusion: The findings reflect the promising potential of quercetin nanocrystals for liver fibrosis prevention.</p

Sirolimus-exuding core-shell nanofibers as an implantable carrier for breast cancer therapy: preparation, characterization, in vitro cell studies, and in vivo anti-tumor activity

OBJECTIVE: Breast cancer accounts for significant mortality worldwide. Here, we develop a localized, sustained-release delivery system for breast cancer therapy. METHODS: Sirolimus (SIR) core-shell nanofibers (NFs) are fabricated by coaxial electrospinning with poly(ε-caprolactone) (PCL) for the core and chitosan and PCL for the shell. The NFs were characterized by SEM, AFM, TEM, XRD, FTIR, water uptake, water contact angle, mechanical properties, drug content, and in vitro release. In vitro and in vivo anticancer effects were investigated. RESULTS: A sustained release behavior is observed during 480 h that is more extended compared to monoaxial NFs. In vitro cytotoxicity and Annexin V/propidium iodide assays indicate that SIR-loaded coaxial NFs are effective in inhibiting proliferation of 4T1 and MCF-7 cells. Implantation of SIR NFs in 4T1 breast tumor-bearing mice inhibits tumor growth significantly compared to free drug. Histopathological examination shows that suppression of tumor growth by SIR NFs is associated with apoptotic cell death. Furthermore, anti-cancer effects are also confirmed by decreased expression levels of Ki-67, MMP-2, and MMP-9. Histological observation of organs, serological analyses, and the lack of body weight changes indicate in vivo safety of SIR NFs. CONCLUSIONS: Altogether, we show here that incorporation of SIR into core-shell NFs could act as an effective drug release depot and induce a sustained antitumor response

Piperine-loaded electrospun nanofibers, an implantable anticancer controlled delivery system for postsurgical breast cancer treatment

Tumorectomy followed by radiotherapy, hormone, and chemotherapy, are the current mainstays for breast cancer treatment. However, these strategies have systemic toxicities and limited treatment outcomes. Hence, there is a crucial need for a novel controlled release delivery system for implantation following tumor resection to effectively prevent recurrence. Here, we fabricated polycaprolactone (PCL)-based electrospun nanofibers containing piperine (PIP), known for chemopreventive and anticancer activities, and also evaluated the impact of collagen (Coll) incorporation into the matrices. In addition to physicochemical characterization such as morphology, hydrophilicity, drug content, release properties, and mechanical behaviors, fabricated nanofibers were investigated in terms of cytotoxicity and involved mechanisms in MCF-7 and 4T1 breast tumor cell lines. In vivo antitumor study was performed in 4T1 tumor-bearing mice. PIP-PCL75-Coll25 nanofiber was chosen as the optimum formulation due to sustained PIP release, good mechanical performance, and superior cytotoxicity. Demonstrating no organ toxicity, animal studies confirmed the superiority of locally administered PIP-PCL75-Coll25 nanofiber in terms of inhibition of growth tumor, induction of apoptosis, and reduction of cell proliferation compared to PIP suspension, blank nanofiber, and the control. Taken together, we concluded that PIP-loaded nanofibers can be introduced as a promising treatment for implantation upon breast tumorectomy