The new era of cholangiocarcinoma treatment: application of nano-based drug delivery systems

Introduction: Targeted drug delivery systems are nanoscale drug carrier molecules designed for improving the communication of cellular and molecular components and biodistribution of tumour targeted drug (chemo) therapeutics. Nanomaterials are generally clusters of molecules, atoms and molecular fragments into extremely small size particles (1-100 nm) in nature. Nanomaterials engineered as self-assembled biodegradable particles were used for targeted drug delivery system. Nanocarriers/ particles should be- capable of transporting high doses of chemotherapeutic drugs/nanomedicines into the targeted tumor cells without disturbing the normal healthy cells. It is also used for construction of novel targeted drug delivery system and future application in nanovaccination and nanotechnology. Conclusion: Multifunctional smart nanoparticles or carries hold out the possibility of effective drug targeted therapeutics in molecular and cellular levels at the earliest stage. Here, we briefly discuss the significance of targeting strategies and drug delivery system and outline the current approaches and future directions in the improvement of tumor targeting nanomedicines.

Recent advances in drug delivery systems for targeting cancer stem cells

Lipid-based drug-delivery systems have evolved from micro- to nano-scale, enhancing the efficacy and therapeutic applications of these delivery systems. Production of lipid-based pharmaceutical nanoparticles is categorized into top-down (fragmentation of particulate material to reduce its average total dimensions) and bottom-up (amalgamation of molecules through chemical interactions creating particles of greater size) production methods. Selection of the appropriate method depends on the physiochemical properties of individual entities within the nanoparticles. The production method also influences the type of nanoparticle formulations being produced. Liposomal formulations and solid-core micelles are the most widely utilized lipid-based nanoparticles, with surface modifications improving their therapeutic outcomes through the production of long-circulating, tissue-targeted and/or pH-sensitive nanoparticles. More recently, solid lipid nanoparticles have been engineered to reduce toxicity toward mammalian cells, while multifunctional lipid-based nanoparticles (i.e., hybrid lipid nanoparticles) have been formulated to simultaneously perform therapeutic and diagnostic functions. This article will discuss novel lipid-based drug-delivery systems, outlining the properties and applications of lipid-based nanoparticles alongside their methods of production. In addition, a comparison between generations of the lipid-based nano-formulations is examined, providing insight into the current directions of lipid-based nanoparticle drug-delivery systems.

The latest advances in nanotechnology have resulted in the development of a targeted drug delivery system. However, in order to efficiently target a molecule to a specific place with a drug delivery system, a specialized drug delivery system is required. The discovery of nanosponge has been a big step toward overcoming challenges such as drug toxicity, low bioavailability, and predictable drug release because they can accept both hydrophilic and hydrophobic drugs. Nanosponges, a newly developed colloidal system, have the potential to address concerns such as medicine toxicity, lower bioavailability, and drug release over a large region because they can be adjusted to operate with both hydrophilic and hydrophobic pharmaceuticals. Nanosponges are small structures with a three-dimensional network and porous hollow. Nanosponges are small structures with a three-dimensional network and porous hollow. They can be easily created by crosslinking cyclodextrins with various chemicals. Because of Cyclodextrin's excellent biocompatibility, stability, and safety, a number of Cyclodextrin-based drug delivery systems have been rapidly developed. The nanosponge drug delivery system has a wide range of applications, including cancer, autoimmune illnesses, theranostic uses, increased bioavailability, and stability. This review delves into the benefits and downsides, preparation procedures, factors influencing their preparation, characterisation techniques, applications, and the most recent advancements in nanosponges. Nanosponges can also act as an efficient carrier of enzymes, proteins, vaccines, and antibodies. The current review focuses on the method of preparation, characterisation, and possible application in drug delivery systems.

Cancer is one of the leading causes of mortality worldwide. Although chemotherapeutic agents have been effectively designed to increase the survival rates of some patients, the designed chemotherapeutic agents necessarily deliver toxic chemotherapeutic drugs to healthy tissues, resulting in serious side effects. Cancer cells can often acquire drug resistance after repeatedly administering current chemotherapeutic agents, restricting their efficacy. Given such obstacles, investigators have attempted to distribute chemotherapeutic agents using targeted drug delivery systems (DDSs), especially nanotechnology-based DDSs. The lipid-based nanoparticles (LBNPs) are a large and complex class of substances utilized to manage various diseases, especially cancers. Liposomes seem to be the most frequently employed LBNPs, owing to their high biocompatibility, bioactivity, stability, and flexibility. Solid lipid NPs and non-structured lipid carriers have lately received a lot of interest. In addition, several reports focused on novel therapies via LBNPs to manage various forms of cancer. In the present research, the latest improvements in applying LBNPs have been shown to deliver different therapeutic agents to cancerous cells and be a quite successful candidate in cancer therapy.

Laminin-derived peptides: Applications in drug delivery systems for targeting.

Background: Oral cancer is a deadly disease affecting worldwide. Despite developments of conventional cancer therapy, there has been little improvement in the survival rates. This culminated in the evolution of a targeted. New Drug Delivery System, discovering novel objectives for successful drug delivery and synergistic combination of anticancer agents to minimize side effects. Objective: The main focus was on understanding the various aspects of different targeted drug delivery vehicles used in the treatment of oral cancer including advantages, disadvantages, and future perspectives. Materials and Methods: A literature search was accomplished from 2005 to 2020 via Google scholar. PubMed, EBSCO, Embase, and Scopus databases along with Clinical trials registries using the terms oral buccal thin films, Hyperthermia and Thermoablation, Intra-tumoral, Photodynamic, Immunotherapy, photothermal, and ultrasound therapy in oral cancer. The articles were scrutinized and those which were not relevant to our search were omitted. Clinical trials on targeted drug delivery systems for Oral Cancer being conducted or completed around the world from various registries of clinical trials have also been searched out and the findings were tabulated in the end. The PRISMA 2020 guidelines were followed. Results: The treatment of oral squamous cell carcinoma (OSCC) mostly depends upon the location, type, and stage of the tumor. Vivid targeted drug delivery systems are being used in the therapeutic interventions of oral cancer as they aim for specific target site delivery and are the most appropriate treatment. Active Pharmacological Ingredient (API) is taken to the targeting site, sparing non-target organs or cells, triggering selective and efficient localization, thereby maximizing the therapeutic index with minimizing toxicity. The successful targeted drug delivery system works on four principles i.e. Retain, Evade, Target and Release, which means loading of sufficient drug into a suitable drug carrier, does not affect body secretions, long duration in circulation, reaching the targeted site and, drug release within the time for effective functioning of the drug. All techniques described in this paper have proven to show effective results. Conclusion: Oral Cancer is an emerging public health problem worldwide. Various conventional therapies are used for treating oral cancer, but they enclose variable degrees of side effects both on the body as well as the cellular microenvironment. With advanced technology, many other aids have been introduced in the field of oncology to treat oral cancer with minimal side effects. All techniques described in this paper have proven to show effective results in the therapeutic interventions of oral cancer. Moreover, they can be used even in combination with conventional drug therapy to show beneficial outcomes. Several clinical trials are being conducted and completed in this aspect to investigate definite results of these therapies, yet robust research is needed for further confirmation.

Special focus issue on targeted drug delivery for inflammatory lung diseases.

Nanoparticle-based targeted drug delivery system (DDS) is one of the major applications of nanotechnology in modern biomedical research. Basically, it comprises of bare or functionalized biocompatible nanoparticles with or without targeting ligands and one or more chemotherapeutic drugs. While the targeting efficacy of DDS without targeting ligands involves passive targeting through enhanced permeability and retention (EPR) effect, DDS containing targeting ligands (e.g., protein, antibodies, peptides, and small molecules) relies on their specificity to cell surface receptors. To achieve combination therapy, two or more chemotherapeutic drugs (exhibiting synergistic effect) are often loaded on nanoparticulate DDS. Besides site-specific delivery, the release of drugs from the DDS and stability of nanomaterials are also important factors to develop an effective nanomedicine that could overcome the disadvantages (e.g., nonspecificity, less bioavailability, and adverse side effect) associated with conventional treatment strategies of different diseases. To comprehend the drug release, stability of nanomaterials as well as ultimate therapeutic applications of DDS, it is highly essential to gradually develop and understand relevant physicochemical and biological characterization techniques. In view of the rapid growth of modern biomedical research involving drug delivery, it might be speculated that many nanomedicines based on DDS would come up in near future for practical therapeutic applications in human.

Systemic chemotherapy for treating tumors often leads to serious systemic side effects and affects patient compliance. Although the emerging technology of drug delivery systems (DDSs) can deliver the required cargo to tumor sites, DDSs are limited due to insufficient targeting ability or deficient pharmacokinetics. Herein, we assembled a novel targeting DDS for precision tumor therapy by applying a tumor-targeting polypeptide cyclic RGD (cRGD)-modified erythrocyte membrane (eM-cRGD) cloaked on zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) with encapsulated doxorubicin (DOX). For a mass ratio of ZIF-8:DOX = 1:1, the loading capacity was up to 49%. The nanoscale-sized targeting DDS promoted NP accumulation in tumor tissues via enhanced permeability and retention (EPR) effects, and the NPs actively targeted ligands and were then transferred to endosomes. The pH-sensitive carriers released higher DOX levels under the low pH mimicking that of a tumor microenvironment and tumor intracellular organelles, allowing enhanced inhibition of cancer cell growth. The cumulative release rate of DOX from DOX@ZIF-8 NPs reached 82.8% at 48 h in acidic conditions of pH = 5.0, while the cumulative release rate of DOX from the DOX@ZIF-8 NPs reached only 24.92% at pH = 7.4. The internalization of the DDS was approximately 44.35% that of the unmodified DDS by immune cells, as confirmed by flow cytometry. In vivo studies verified that the RGD-modified DDS had the ability to prolong blood circulation (t1/2 = 6.81 h), enhancing the tumor-specific accumulation of NPs by means of the integrin αvβ3 receptor-mediated pathway, which was further valuated in mice bearing human cervical cancer (HeLa) cells, and yielding a significant antitumor effect; the tumor inhibition rate was as high as 85.46%. Under the same conditions, the blood circulation half-life of the unmodified DDS was only 3.22 h, and the tumor inhibition rate of free DOX was 81.34%. Moreover, the RGD modified with a carrier could achieve a satisfactory chemotherapeutic effect while minimizing side effects. In summary, our novel targeting DDS could contribute to the development of intelligent DDSs for tumor precision therapy.

10 - Oxazoline and caprolactone based polymeric materials

The application of macromolecules as vehicles for anticancer drug delivery is a burgeoning field of interest. One of the hallmarks of using such systems, however, is that they must be capable of site-specific drug delivery. As such, augmenting the targeting of drug delivery systems to specified sites is paramount. To date, a number of synthetic strategies have been utilized to introduce targeting moieties to macromolecular drug delivery systems to enhance specific targeting. This scheme frequently involves the introduction of some type of biologically recognizable marker to the delivery system. Biological evaluations have substantiated the rationale that introducing targeting groups can significantly increase specificity. This concise review will attempt to encompass what strategies have been done to increase the specificity of macromolecular anticancer drug delivery systems along with their biological activities.

Natural and synthetic polymers have been used in pharmaceutical industry for many years and have important role in the development of the conventional dosage forms or for manufacturing of various drug packaging materials. In recent years, their important application resides in the development of the most sophisticated drug delivery systems where polymers are used as a drug carrier. Biodegradable polymers are particularly attractive for application in drug delivery systems since, once introduced into the human body, they do not require removal or additional manipulation. Their degradation products are normal metabolites of the body or products that can be metabolized and easily cleared from the body. Among that, synthetic polymers offer a wide variety of compositions with adjustable properties. These materials open the possibility of developing new drug delivery systems with specific properties (chemical, interfacial, mechanical and biological) for a given application, simply by changing the building blocks or the preparation technique. Such designed complex drug delivery systems where polymers are used as functional excipients have numerous advantages such as localized delivery of drug, sustained delivery of drug, stabilization of the drug, prevention of drug’s adverse side-effects, reduction of dosing frequency, minimization of drug concentration fluctuations in plasma level, improved drug utilization and patient compliance. There are range of differently designed drug delivery systems and their description and mechanism of action will be presented in this paper together with the prominent role of the polymers for each particular system. Additionally, most commonly used synthetic biodegradable polymers in drug delivery systems will be presented together with their degradation mechanism.

Chitosan mediated smart photodynamic therapy based novel drug delivery systems- a futuristic view

Niosomes are vesicles, which are formulated by hydrating the mixture of cholesterol, non-ionic surfactant and other biodegradable lipids. Niosomes increase the drug activity as compare to their conventional dosage form of a drug. Niosomes can be used as carrier of amphiphilic and lipophilic drugs. Niosomes may overcome the issues related to instability, fast degradation, low bioavailability, and insolubility of medications. The structure of niosomes either multilamellar or unilamellar, is depends on the method of formulation. Niosomes contain very efficient drug delivery potential for site-specific delivery of anti-cancer, anti-infective agents, etc. Niosomes are stable as well as cost effective carriers as compared with other drug formulations. Niosomes also have various applications in parental drug delivery system, topical drug delivery system, oral drug delivery system and novel drug delivery system such as targeted drug delivery system and controlled drug release system.