Construction of an exosome-functionalized graphene oxide based composite bionic smart drug delivery system and its anticancer activity

Graphene oxide has covalently modified by chito oligosaccharides and γ-polyglutamic acid to form GO-CO-γ-PGA, which exhibits excellent performance as a drug delivery carrier, but this carrier did not have the ability to actively target. In this study, the targeting property of breast cancer tumor cell exosomes was exploited to give GO-CO-γ-PGA the ability to target breast tumor cells (MDA-MB-231), and the drug mitoxantrone (MIT) was loaded to finally form EXO-GO-CO-γ-PGA-MIT with a loading capacity of 1.39 mg/mg. The pH response of EXO-GO-CO-γ-PGA showed a maximum cumulative release rate of 56.59% (pH 5.0) and 6.73% (pH 7.4) for MIT at different pH conditions. pH 7.4). In vitro cellular assays showed that EXO-GO-CO-γ-PGA-MIT was more potent in killing MDA-MB-231 cells due to its targeting ability and had a significantly higher pro-apoptotic capacity compared to GO-CO-γ-PGA-MIT. The results showed that this bionic nano-intelligent drug delivery system has good drug slow release function, can increase the local drug concentration of tumor and enhance the pro-apoptotic ability of MIT, so this newly synthesized bionic drug delivery carriers (EXO-GO-CO-γ-PGA-MIT) has potential application in breast cancer treatment.

Synthesis and Characterization of Acrylamide/Acrylic Acid Co-Polymers and Glutaraldehyde Crosslinked pH-Sensitive Hydrogels

This project aims to synthesize and characterize the pH-sensitive controlled release of 5-fluorouracil (5-FU) loaded hydrogels (5-FULH) by polymerization of acrylamide (AM) and acrylic acid (AA) in the presence of glutaraldehyde (GA) as a crosslinker with ammonium persulphate as an initiator. The formulation’s code is named according to acrylamide (A1, A2, A3), acrylic acid (B1, B2, B3) and glutaraldehyde (C1, C2, C3). The optimized formulations were exposed to various physicochemical tests, namely swelling, diffusion, porosity, sol gel analysis, and attenuated total reflection-Fourier transform infrared (ATR-FTIR). These 5-FULH were subjected to kinetic models for drug release data. The 5-FU were shown to be soluble in distilled water and phosphate buffer media at pH 7.4, and sparingly soluble in an acidic media at pH 1.2. The ATR-FTIR data confirmed that the 5-FU have no interaction with other ingredients. The lowest dynamic (0.98 ± 0.04% to 1.90 ± 0.03%; 1.65 ± 0.01% to 6.88 ± 0.03%) and equilibrium swelling (1.85 ± 0.01% to 6.68 ± 0.03%; 10.12 ± 0.02% to 27.89 ± 0.03%) of formulations was observed at pH 1.2, whereas the higher dynamic (4.33 ± 0.04% to 10.21 ± 0.01%) and equilibrium swelling (22.25 ± 0.03% to 55.48 ± 0.04%) was recorded at pH 7.4. These findings clearly indicated that the synthesized 5-FULH have potential swelling characteristics in pH 6.8 that will enhance the drug’s release in the same pH medium. The porosity values of formulated 5-FULH range from 34% to 62% with different weight ratios of AM, AA, and GA. The gel fractions data showed variations ranging from 74 ± 0.4% (A1) to 94 ± 0.2% (B3). However, formulation A1 reported the highest 24 ± 0.1% and B3 the lowest 09 ± 0.3% sol fractions rate among the formulations. Around 20% drug release from the 5-FULH was found at 1 h in an acidic media (pH1.2), whereas >65% of drug release (pH7.4) was observed at around 25 h. These findings concluded that GA crosslinked 5-FU loaded AM and AA based hydrogels would be a potential pH-sensitive oral controlled colon drug delivery carrier.

Enhancement of the Topical Bioavailability and Skin Whitening Effect of Genistein by Using Microemulsions as Drug Delivery Carriers

Genistein, the most abundant isoflavone of the soy-derived phytoestrogen compounds, is a potent antioxidant and inhibitor of tyrosine kinase, which can inhibit UVB-induced skin carcinogenesis in hairless mice and UVB-induced erythema on human skin. In current study, genistein-loaded microemulsions were developed by using the various compositions of oil, surfactants, and co-surfactants and used as a drug delivery carrier to improve the solubility, peremability, skin whitening, and bioavailbility of genistein. The mean droplet size and polydispersity index of all formulations was less than 100 nm and 0.26 and demonstrated the formation of microemulsions. Similarly, various studies, such as permeation, drug skin deposition, pharmacokinetics, skin whitening test, skin irritation, and stability, were also conducted. The permeability of genistein was significantly affected by the composition of microemulsion formulation, particular surfactnat, and cosurfactant. In-vitro permeation study revealed that both permeation rate and deposition amount in skin were significantly increased from 0.27 μg/cm2·h up to 20.00 μg/cm2·h and 4.90 up to 53.52 μg/cm2, respectively. In in-vivo whitening test, the change in luminosity index (ΔL*), tended to decrease after topical application of genistein-loaded microemulsion. The bioavailability was increased 10-fold by topical administration of drug-loaded microemulsion. Conclusively, the prepared microemulsion has been enhanced the bioavailability of genistein and could be used for clinical purposes.

A Novel Drug Delivery of Microspheres

Microspheres are multiparticulate drug delivery systems that distribute medications at a predetermined rate to a specific region. Microspheres are free-flowing powders manufactured from biodegradable proteins or synthetic polymers, with particle sizes ranging from 1 to 1000 micrometers. Benefits of using microspheres in medication delivery, bone tissue manufacture, and pollutant absorption and desorption by regeneration .The study demonstrates how microsphere parameters are planned and measured. Bioadhesive microspheres, polymeric microspheres, magnetic microspheres, floating microspheres, and radioactive microspheres are only a few examples of complicated microspheres. Cosmetics, oral medication administration, target drug delivery, ocular drug delivery, gene delivery, and other industries covered in the paper could all benefit from microspheres. To ensure best therapeutic effectiveness, the agent must be delivered to target tissue at an optimal amount during the appropriate timeframe, with low toxicity and adverse effects. There are several methods for delivering the therapeutic substance to the target site in a controlled manner. The use of microspheres as medication carriers is one such technique. The value of microspheres as a novel drug delivery carrier to accomplish site-specific drug delivery was discussed in this article. Keywords: Microspheres, method of preparations, polymer bioadhesion, types of microspheres.

Mesenchymal stem cells-derived exosomes for drug delivery

Exosomes are extracellular vesicles secreted by various cells, mainly composed of lipid bilayers without organelles. In recent years, an increasing number of researchers have focused on the use of exosomes for drug delivery. Targeted drug delivery in the body is a promising method for treating many refractory diseases such as tumors and Alzheimer's disease (AD). Finding a suitable drug delivery carrier in the body has become a popular research today. In various drug delivery studies, the exosomes secreted by mesenchymal stem cells (MSC-EXOs) have been broadly researched due to their immune properties, tumor-homing properties, and elastic properties. While MSC-EXOs have apparent advantages, some unresolved problems also exist. This article reviews the studies on MSC-EXOs for drug delivery, summarizes the characteristics of MSC-EXOs, and introduces the primary production and purification methods and drug loading methods to provide solutions for existing problems and suggestions for future studies.

Ultrasound-Induced Microbubble Cavitation Combined with Paclitaxel-Loaded Nanoparticles for the Elimination of PC-3 Cells in vitro

Castration-resistant prostate cancer (CRPC) and its metastases are the main reasons for the high mortality of prostate cancer. Currently, paclitaxel (PTX)-based chemotherapeutics are used as first-line drugs to treat CRPC, but this treatment does not show good effects and is accompanied by serious side effects, which may be because intravenously injected chemotherapeutic drugs have difficulties gathering at the tumor site. Therefore, a safe and effective drug delivery carrier is urgently needed to enhance the therapeutic effects of chemotherapeutic drugs against CRPC. Methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) nanoparticles (NPs) have shown high drug encapsulation efficiency and good therapeutic effects against ovarian cancer and pancreatic cancer, but there are few studies on their treatment against CRPC. To expand the applications of mPEG-PLGA-PLL NPs, in this study, mPEG-PLGA-PLL NPs loaded with PTX (PTX-NPs) were synthesized. The synthesized PTX-NPs had a uniform particle size and no obvious aggregation. PTX-NPs can be uptaked by PC-3 cells, which significantly promotes the inhibition of proliferation and apoptosis effects of PTX on cells and reduces the expression levels of CDK6, Cyclin D1 and Bcl-2 (cyclins and an apoptosis inhibitor), and these effects can be further enhanced by ultrasound-induced microbubble cavitation (UIMC). Our research provides a new nanocarrier for the treatment of CRPC, laying the foundation for further research in the future.

Gum Acacia Functionalized Colloidal Gold Nanoparticles of Letrozole as Biocompatible Drug Delivery Carrier for Treatment of Breast Cancer

The most prevalent malignancy among postmenopausal women is breast cancer. It is one of the leading causes of cancer-related mortality among women. Letrozole (LTZ) is a clinically approved inhibitor for breast cancer in postmenopausal women. However, due to poor aqueous solubility, non-specific binding, unwanted toxicity, and poor blood circulation hampered its clinical applications. To maximize the pharmacological effects and minimize the side effects, inorganic nanoparticles are a good alternative. Due to excellent biocompatibility and minimum cytotoxicity, gold nanoparticles (AuNPs) offer distinct benefits over other metal nanoparticles. Emerging as attractive components, AuNPs and Gum acacia (GA) have been extensively studied as biologically safe nanomaterials for the treatment of cancers. This study reports the synthesis and characterization of GA stabilized gold nanoparticles (GA-AuNPs) of LTZ for breast cancer treatment. The observed particle size of optimized LTZ @ GA-AuNPs was 81.81 ± 4.24 nm in size, 0.286 ± 0.143 of polydispersity index (PDI) and −14.6 ± −0.73 mV zeta potential. The biologically synthesized LTZ @ GA-AuNPs also demonstrated dose-dependent cytotoxicity against the human breast cancer cell line MCF-7, with an inhibitory concentration (IC50) of 3.217 ± 0.247. We determined the hemolytic properties of the LTZ @ GA-AuNPs to evaluate the interaction between the nanoparticles and blood components. Results showed that there is no interaction between LTZ @ GA-AuNPs and blood. In conclusion, the findings indicate that LTZ @ GA-AuNPs has significant potential as a promising drug delivery carrier for treating breast cancer in postmenopausal women.

Human Serum Albumin: A Novel Drug Delivery Carrier System

Serum albumin, often referred to simply as albumin, is a globular protein that in humans is encoded by the ALB gene. Albumin is a multifaceted, highly soluble, stable, nontoxic, non-poisonous, biocompatible and biodegradable plasma protein. Albumin has been widely studied as a protein carrier for drug delivery. Because of its versatile nature, it can also be used for the delivery of the hormones, metals and fatty acids by binding to its specific binding sites. Various studies revealed that albumin can be used to increase the circulating half-life and bioavailability of drug molecules which are smaller than the renal filtration threshold and are rapidly lost from the circulation leading to limiting therapeutic potential. This review article presents advantages, disadvantages, functions, importance, different nanoparticles that can be crowned with an albumin and the special features of albumin as a drug carrier, and how the understanding of these features is currently being employed to optimize the circulatory half-life albumin.