Stimuli-Responsive Polymeric Nanocarriers for Drug Delivery, Imaging, and Theragnosis

In the past few decades, polymeric nanocarriers have been recognized as promising tools and have gained attention from researchers for their potential to efficiently deliver bioactive compounds, including drugs, proteins, genes, nucleic acids, etc., in pharmaceutical and biomedical applications. Remarkably, these polymeric nanocarriers could be further modified as stimuli-responsive systems based on the mechanism of triggered release, i.e., response to a specific stimulus, either endogenous (pH, enzymes, temperature, redox values, hypoxia, glucose levels) or exogenous (light, magnetism, ultrasound, electrical pulses) for the effective biodistribution and controlled release of drugs or genes at specific sites. Various nanoparticles (NPs) have been functionalized and used as templates for imaging systems in the form of metallic NPs, dendrimers, polymeric NPs, quantum dots, and liposomes. The use of polymeric nanocarriers for imaging and to deliver active compounds has attracted considerable interest in various cancer therapy fields. So-called smart nanopolymer systems are built to respond to certain stimuli such as temperature, pH, light intensity and wavelength, and electrical, magnetic and ultrasonic fields. Many imaging techniques have been explored including optical imaging, magnetic resonance imaging (MRI), nuclear imaging, ultrasound, photoacoustic imaging (PAI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). This review reports on the most recent developments in imaging methods by analyzing examples of smart nanopolymers that can be imaged using one or more imaging techniques. Unique features, including nontoxicity, water solubility, biocompatibility, and the presence of multiple functional groups, designate polymeric nanocues as attractive nanomedicine candidates. In this context, we summarize various classes of multifunctional, polymeric, nano-sized formulations such as liposomes, micelles, nanogels, and dendrimers

Selective targeting of cancer signaling pathways with nanomedicines: challenges and progress

Cancer is one of the leading causes of death worldwide. Regardless of advances in understanding the molecular mechanics of cancer, its treatment is still lacking and the death rates for many forms of the disease remain the same as six decades ago. Although a variety of therapeutic agents and strategies have been reported, these therapies often failed to provide efficient therapy to patients as a consequence of the inability to deliver right and adequate chemotherapeutic agents to the right place. However, the situation has started to revolutionize substantially with the advent of novel ‘targeted’ nanocarrier-based cancer therapies. Such therapies hold great potential in cancer management as they are biocompatible, tailored to specific needs, tolerated and deliver enough drugs at the targeted site. Their use also enhances the delivery of chemotherapeutics by improving biodistribution, lowering toxicity, inhibiting degrada- tion and increasing cellular uptake. However, in some instances, nonselective targeting is not enough and the inclusion of a ligand moiety is required to achieve tumor targeting and enhanced drug accumulation at the tumor site. This contemporary review outlines the targeting potential of nanocarriers, highlighting the essentiality of nanoparticles, tumor-associated molecular signaling pathways, and various biological and pathophysiological barriers

Biopolymer-Capped Pyrazinamide-Loaded Colloidosomes : In Vitro Characterization and Bioavailability Studies

This study aimed to prepare colloidosome particles loaded with pyrazinamide (PZA). These drug-loaded colloidosomes were prepared using an in situ gelation technique using a central composite design with a shell made of calcium carbonate (CaCO3) particles. Optimal amounts of 150 mg of CaCO3, sodium alginate (2%), and 400 mg of poly(3-hydroxybutyrate-co-3-hydroxy valerate) (PHBV) concentration resulted in the maximum drug loading and efficient release profile. Field emission scanning electron microscopy results showed spherical porous particles with a good coating of the PHBV polymer. Additionally, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetric and differential thermal analysis (TGA-DTA), and X-ray diffraction (XRD) analysis showed good compatibility between the drug and excipients. The pharmacokinetic studies demonstrated that the drug-loaded colloidosomes resulted in 4.26 times higher plasma drug concentrations with Cmax values of 32.386 ± 2.744 mcg/mL (PZA solution) and 115.868 ± 53.581 mcg/mL (PZA-loaded colloidosomes) and AUC0–t values of 61.24 mcg-h/mL (PZA solution) and 260.9 mcg-h/mL (PZA-loaded colloidosomes), indicating that colloidosomes have the potential to be effective drug carriers for delivering PZA to the target site.Peer reviewe

Laponite-based nanomaterials for biomedical applications: A review

Laponite based nanomaterials (LBNMs) are highly diverse regarding their mechanical, chemical, and structural properties, coupled with shape, size, mass, biodegradability and biocompatibility. These ubiquitous properties of LBNMs make them appropriate materials for extensive applications. These have enormous potential for effective and targeted drug delivery comprised of numerous biodegradable materials which results in enhanced bioavailability. Moreover, the clay material has been explored in tissue engineering and bioimaging for the diagnosis and treatment of various diseases. The material has been profoundly explored for minimized toxicity of nanomedicines. The present review compiled relevant and informative data to focus on the interactions of laponite nanoparticles and application in drug delivery, tissue engineering, imaging, cell adhesion and proliferation, and in biosensors. Eventually, concise conclusions are drawn concerning biomedical applications and identification of new promising research directions

Receptor-based combinatorial nanomedicines: a new hope for cancer management

Nanotechnology-based drug-delivery systems, as an anticancer therapy tool, have shown significant potentials for the diagnosis and treatment of cancer. Recent studies have demonstrated that cancer therapy could be efficiently achieved by combinatorial therapies, approaches using multiple drug regimens for targeting cancers. However, their usages have been limited due to shorter half-lives of chemotherapeutic agents, insignificant targetability to tumor sites and suboptimal levels of co-administered conventional drug moieties. Thus, nanotechnology-based drug-delivery systems with effective targetability have played a crucial role to overcome the limitations and challenges associated with conventional therapies and also have provided greater therapeutic efficacy. Herein, the authors have focused on various drug-incorporated combinatorial nanocarrier systems, the significance of various receptors-associated strategies, and various targeted delivery approaches for chemotherapeutic agents

First-order derivative spectrophotometric method for simultaneous determination of brinzolamide and timolol maleate in ophthalmic formulation

Multi-analyte determination techniques are favored over those that can only determine a single analyte at a time because they enable resource savings (cost, time, and solvents) and reduce generated waste and the number of samples required for analysis. This research presents a novel method for the simultaneous determination of brinzolamide (BRZ) and timolol maleate (TML) in pharmaceutical ophthalmic preparations using first-order derivative UV–Visible spectroscopy. The proposed approach is environmentally friendly and yet to be previously reported in the literature. In this approach, the peak amplitude of BRZ was quantified at the zero-crossing point of TML, i.e., 248.80 nm, whereas TML was determined by measuring absorbance at 297.60 nm. The developed method was validated according to the International Council for Harmonisation guidelines Q2(R1). The developed method was linear with excellent correlation coefficient values (R2 > 0.9998) in the range of 4 – 24 µg/ml for BRZ and 5 – 25 µg/ml for TML. The accuracy and precision results were within limits for both the analytes (%Relative standard deviation, RSD <2 %). The proposed method demonstrated LOD = 0.38 µg/mL for BRZ and 0.98 µg/mL for TML; LOQ = 0.91 µg/mL for BRZ and 2.99 µg/mL for TML), and was found to be selective, and robust. Lastly, the novel Analytical GREEnness (AGREE) metrics, the analytical eco-scale, and the green analytical procedure index (GAPI) were utilized to evaluate the developed technique's environmental sustainability and compare it to the HPLC method

Nano-scale drug delivery systems for carboplatin: A comprehensive review

Carboplatin (CRBP) is a chemotherapeutic agent based on platinum that has applications in the effective management of ovarian, testis, cervical, neck, head, and small cell lung cancer. CRBP prevents duplication and transcription by binding to the DNA of tumor cells to inhibit the growth and division of cancer cells. CRBP has some limitations such as destroying normal cells alongside cancer cells and being poor at uptake by the cells, leading to the need for high doses, which has prompted significant attention to develop a targeted and localized delivery system that is effective for this anticancer drug. It is common to use CRBP in drug combination therapy. However, there are some disadvantages that could be overcome with nanoparticulate systems. Nano-engineered delivery systems can be an efficient approach to enhancing the cellular uptake and accumulation of CRBP, leading to improving the therapeutic potential with negligible toxicity. CRBP has been encapsulated into various nano-delivery systems, including polymer-based nanocarriers and micelles, protein nanoparticles, lipid-based nanoparticles (liposomes and solid lipid nanoparticles), silica-based nanostructures, carbon nanoparticles and etc. Moreover, there is growing interest in stimuli-responsive delivery systems for cancer-targeted delivery using modes such as induced temperature changes, electric/magnetic fields, pH, ultrasound waves, light, and laser. Cancer targeting by drug delivery systems, owing to their selective targeting, efficacy, biocompatibility and high drug payload, provides an attractive alternative treatment; however, there are technical, therapeutic, manufacturing and clinical barriers that limit their use. In this regard, the need for robust analytical methods to determine biodistribution, PK and PD profile of liposomes was highlighted in addition to a critical gap between efficient preclinical to clinical efficacy predictive modeling. Systems with the ability of co-delivery also could be useful to decrease drug toxicity on healthy tissues and improve the bioavailability of CRBP