Encapsulation of zinc-rifampicin complex into transferrin-conjugated silver quantum-dots improves its antimycobacterial activity and stability and facilitates drug delivery into macrophages.
In order to improve the chemotherapy of tuberculosis, there is an urgent need to enhance the efficacy of existing agents and also to develop more efficient drug delivery systems. Here, we synthesized a novel anti-TB drug complex consisting of zinc and rifampicin (Zn-RIF), and encapsulated it into transferrin-conjugated silver quantum-dots (Zn-RIF-Tf-QD) to improve delivery in macrophages. Successful synthesis of Zn-RIF and Zn-RIF-Tf-QD was confirmed by UV/Vis-spectroscopy, TEM, FTIR, photoluminescence, XRD, XPS, and NMR. The sizes of silver QDs and transferrin-conjugated QDs were found to be in the range of 5–20 nm. Activity assays showed that Zn-RIF-Tf-QD exhibited 10-fold higher antibacterial activity against Mycobacterium smegmatis and Mycobacterium bovis-BCG as compared to Zn-RIF, RIF and Zn. Immunofluorescence studies showed that Zn-RIF-Tf-QD-conjugates were actively endocytosed by macrophages and dendritic cells, but not by lung epithelial cells. Treatment with Zn-RIF-Tf-QD efficiently killed mycobacteria residing inside macrophages without exhibiting cytotoxicity and genotoxicity. Moreover, the conjugates remained stable for upto 48 h, were taken up into the late endosomal compartment of macrophages, and released the drug in a sustainable manner. Our data demonstrate that Zn-RIF-Tf-QDs have a great potential as anti-TB drugs. In addition, transferrin-conjugated QDs may constitute an effective drug delivery system for tuberculosis therapy.
- Research Article
17
- 10.1080/09205063.2021.1902175
- Mar 23, 2021
- Journal of Biomaterials Science, Polymer Edition
Considerable research exercises have been directed towards the development of efficient and safe drug delivery systems. Various materials are used in different pharmaceutical formulations for the development of efficient drug delivery systems in the treatment of disease. Biopolymers are a choice of research as an excipient delivery system due to their biodegradability, low toxicity, safe, stable, and renewable nature. Biopolymers are naturally occurring polymers or polymer matrix composites, that are extracted from animals, bacteria, fungi, and plants. Cellulose, starches are carbohydrate-based polymers, and wool, silk, gelatin, and collagen are protein-based biopolymers. Biopolymers are obtained from various sources but biopolymers, that belong to the carbohydrate origin, have been found very promising in drug delivery through various routes. The review mainly focuses on the biopolymers currently in use for buccal-mediated pharmaceutical drug delivery systems because the buccal route is an efficient drug delivery system that allows direct systemic circulation of drugs. It also prevents the hydrolysis of the drug molecule in the gastrointestinal tract and thus increases the bioavailability of the drug. The present review discusses the overview of other drug delivery routes, challenges with conventional drug delivery systems, pharmaceutical applications of some biopolymers used in buccal drug delivery systems, that are published recently, currently in use, or used over the past decade.
- Research Article
26
- 10.1002/jbm.b.31730
- Sep 28, 2010
- Journal of Biomedical Materials Research Part B: Applied Biomaterials
Modified strontium-containing hydroxyapatite (Sr-HA) bone cement was loaded with gentamicin sulfate to generate an efficient bioactive antibiotic drug delivery system for treatment of bone defects. Gentamicin release and its antibacterial property were determined by fluorometric method and inhibition of Staphylococcus aureus (S. aureus) growth. Gentamicin was released from Sr-HA bone cement during the entire period of study and reached around 38% (w/w) cumulatively after 30 days. Antibacterial activity of the gentamicin loaded in the cements is clearly confirmed by the growth inhibition of S. aureus. The results of the amount and duration of gentamicin release suggest a better drug delivery efficiency in Sr-HA bone cement over polymethylmethacrylate bone cement. Bioactivity of the gentamicin-loaded Sr-HA bone cement was confirmed with the formation of apatite layer with 1.836 ± 0.037 μm thick on day 1 and 5.177 ± 1.355 μm thick on day 7 after immersion in simulated body fluid. Compressive strengths of the gentamicin-loaded Sr-HA cement reached 132.60 ± 10.08 MPa, with a slight decrease from the unloaded groups by 4-9%. Bending moduli of Sr-HA cements with and without gentamicin were 1.782 ± 0.072 GPa and 1.681 ± 0.208 GPa, respectively. On the contrary, unloaded Sr-HA cement obtained slightly larger bending strength of 35.48 ± 2.63 MPa comparing with 33.00 ± 1.65 MPa for loaded cement. No statistical difference was found on the bending strengths and modulus of gentamicin-loaded and -unloaded Sr-HA cements. Sr-HA bone cement loaded with gentamicin was proven to be an efficient drug delivery system with uncompromised mechanical properties and bioactivity.
- Research Article
70
- 10.1016/j.molliq.2023.123888
- Dec 27, 2023
- Journal of Molecular Liquids
Simulation-based approaches for drug delivery systems: Navigating advancements, opportunities, and challenges
- Conference Article
5
- 10.1109/nebec.2014.6972756
- Apr 1, 2014
Polymeric nanoparticles (NPs) are emerging as promising protein drug delivery carriers for both oral and parenteral methods of administration. Understanding the mechanism of protein loading is imperative for designing more efficient drug delivery systems. However, the process of protein loading and the resulting structure of the polymeric NPs remain unclear. In this study, insulin and poly (lactic-co-glycolic acid) - poly (ethylene glycol) (PLGA-PEG) NPs are used as model protein and polymeric drug delivery carrier, respectively. We show that electrostatic interactions between the protein drug and the polymer play a key role in mediating the formation of these NPs. It is also observed that majority of the protein molecules interact with the corona of the NPs instead of the core. These results provide a deeper insight into the formation of protein loaded polymeric NPs synthesized by the nanoprecipitation method, which can lead to the development of more efficient future protein drug delivery systems.
- Research Article
1
- 10.55549/ephels.138
- Dec 1, 2024
- The Eurasia Proceedings of Health, Environment and Life Sciences
Lung cancer is one of the most prevalent cancers and it is also the primary cause of cancer-related mortality globally. However, due to variations in tobacco use patterns, exposure to environmental risk factors, and genetics, lung cancer incidence and mortality rates vary significantly worldwide. Since smoking is the primary risk factor for lung cancer, developing more effective therapeutic strategies and innovative drug delivery systems may help to raise the disease's survival rates. In this study, a novel pH-sensitive nanocarrier based on a composite of a two-dimensional hexagonal boron nitride (2D-hBN) with unique properties was synthesized to deliver Doxorubicin (DOX). Firstly, bulk hBN powder was exfoliated with a sodium cholate salt, sonicated, and centrifuged to obtain the as-prepared 2D-hBN nanocarriers, and finally, DOX was entrapped for targeted drug delivery and tumor therapy. High DOX loading and entrapment efficiency (LE% and EE%, respectively) were obtained. The EE% and LE% for sodium cholate exfoliated 2D-hBN obtained were 84.50% and 25.48%, respectively. In vitro drug release experiments demonstrated a pH-sensitive non-Fickian release profile with a release percentage of 73.5%. Preliminary in-vitro cytotoxicity was done via MTT assay, using the human lung adenocarcinoma cell line (A549), and the 2D-hBN@DOX nanocomposites were shown to drastically reduce the viability of the cancer cells compared to 2D-hBN, indicating the great efficacy of the former nanocomposites in hindering the proliferation of cancer cells.
- Research Article
64
- 10.1039/c2py20981k
- Jan 1, 2013
- Polymer Chemistry
Efficient delivery systems should be stable in blood circulation, with efficient cellular uptake and rapid drug release in cancer cells. Herein, we synthesized P(2-(methacryloyloxy)-ethyl phosphorylcholine)-b-P(2-methoxy-2-oxoethyl methacrylate) via atom transfer radical polymerization. Doxorubicin (DOX) was linked to the polymer via a pH-responsive hydrazone bond. The polymer prodrug had high DOX content (10.6 wt%) and was able to self-assemble to form core–shell structured micelles. Dynamic light scattering showed that the average size of the micelles was 142.3 nm, which is the ideal size for the enhanced permeability and retention (EPR) effect. The shell of the micelles was composed of phosphorylcholine, which imitated the structure of cell membranes. Studies of intracellular uptake demonstrated that the prodrug micelles were internalized effectively by cancer cells. An in vitro release study indicated that the release of DOX at pH 5.0 was much faster than that at pH 7.4. Moreover, in vitro cytotoxicity showed that this polymer prodrug inhibited the growth of cancer cells remarkably, demonstrating its potential for use as an efficient drug delivery system.
- Research Article
383
- 10.3390/gels9070523
- Jun 27, 2023
- Gels
Polymer-based hydrogels are hydrophilic polymer networks with crosslinks widely applied for drug delivery applications because of their ability to hold large amounts of water and biological fluids and control drug release based on their unique physicochemical properties and biocompatibility. Current trends in the development of hydrogel drug delivery systems involve the release of drugs in response to specific triggers such as pH, temperature, or enzymes for targeted drug delivery and to reduce the potential for systemic toxicity. In addition, developing injectable hydrogel formulations that are easily used and sustain drug release during this extended time is a growing interest. Another emerging trend in hydrogel drug delivery is the synthesis of nano hydrogels and other functional substances for improving targeted drug loading and release efficacy. Following these development trends, advanced hydrogels possessing mechanically improved properties, controlled release rates, and biocompatibility is developing as a focus of the field. More complex drug delivery systems such as multi-drug delivery and combination therapies will be developed based on these advancements. In addition, polymer-based hydrogels are gaining increasing attention in personalized medicine because of their ability to be tailored to a specific patient, for example, drug release rates, drug combinations, target-specific drug delivery, improvement of disease treatment effectiveness, and healthcare cost reduction. Overall, hydrogel application is advancing rapidly, towards more efficient and effective drug delivery systems in the future.
- Research Article
12
- 10.1016/j.jddst.2019.02.022
- Feb 25, 2019
- Journal of Drug Delivery Science and Technology
Enhancing the anti-cancer therapeutic efficacy by optimizing molecular weight of metal-free fully alternating semi-aromatic polyester as nano-drug carriers
- Research Article
26
- 10.1186/s11671-022-03673-9
- Mar 22, 2022
- Nanoscale Research Letters
Nanoparticles have unique properties and high design flexibility, which are thought to be safe, site-specific, and efficient drug delivery systems. However, nanoparticles as exogenous materials can provide recognition and be eliminated by the body’s immune system, which considerably restricts their applications. To overcome these drawbacks, natural cell membrane coating method has attracted great attention in the field of drug delivery systems, which can prolong nanoparticles blood circulation time and avoiding the capture as well as elimination by the body immune system. Biomimetic nanoparticles via a top-down approach can avoid the laborious group modified engineering and keep the integrity of cell membrane structure and membrane antigens, which can be endowed with unique properties, such as immune escape, longer blood circulation time, targeting delivery and controlling drugs sustain-release. At the present research, erythrocyte membrane, cancer cell membrane, platelet membrane, lymphocyte membrane and hybrid membrane have been successfully coated into the surface of nanoparticles to achieve biological camouflage. Thus, integrating various kinds of cell membranes and nanoparticles into one system, the biomimetic nanoparticles can inherit unique biofunction and drug delivery properties to exhibit tumor targeting-delivery and antitumor outcomes. In this article, we will discuss the prospects and challenges of some basic cell membrane cloaking nanoparticles as a drug delivery system for cancer therapy.
- Research Article
20
- 10.1016/j.colsurfb.2018.06.008
- Jun 6, 2018
- Colloids and Surfaces B: Biointerfaces
Real-time imaging tracking of a dual-fluorescent drug delivery system based on doxorubicin-loaded globin- polyethylenimine nanoparticles for visible tumor therapy.
- Research Article
162
- 10.1016/j.msec.2017.05.049
- May 11, 2017
- Materials Science and Engineering: C
Methotrexate-loaded nitrogen-doped graphene quantum dots nanocarriers as an efficient anticancer drug delivery system
- Book Chapter
5
- 10.1007/978-3-031-12658-1_12
- Jan 1, 2022
The treatment of infectious diseases and immunizations has experienced a paradigm shift in recent years. With the advent of biotechnology and genetic engineering, not only have various disease-specific biologicals been developed, but an emphasis has also been focused on the effective delivery of such biologicals. The majority of active pharmaceutical ingredients exhibit poor bioavailability, biological degradation, and unexpected underlying adverse effects. To overcome these limitations, developing efficient and new drug delivery systems is crucial in terms of their efficacy across several administration routes, including cutaneous, oral, topical, parenteral, and pulmonary. To accomplish these goals effectively, targeted delivery of drugs/genes to specific tissues/cells has been extensively investigated. The applications of liposomes and niosomes may have advantages over other nanoparticles (NPs) due to their excellent biocompatibility, increased drug loading capacity, and scalability. Liposomes have already gained a significant impact on a number of biomedical fields. They have been proven to be advantageous in stabilizing bioactive components, removing obstacles to cellular and tissue absorption, and optimizing drug biodistribution to target areas in vivo. Encapsulated chemicals are delivered to specific sites while reducing systemic toxicity. Liposomes are promising delivery technologies because of their versatile physicochemical and biophysical properties. Niosomes (nonionic surfactant vesicles), which are being investigated as innovative drug delivery methods, have been shown to enhance the solubility and stability of natural medicinal compounds and other pharmaceutical ingredients. They were developed to facilitate the targeted and controlled release of natural bioactive ingredients. As a result, nanosystems such as liposomes and niosomes have developed into effective methods for enhancing the targeted delivery of drugs and genes. This chapter will provide an overview of the techniques for preparing niosomes and liposomes, the types of niosomes and liposomes, and their characterization and uses in targeted drug and gene delivery systems.KeywordsGenetic engineeringNiosomesLiposomesNanoparticles (NPs)
- Research Article
7
- 10.1016/j.actbio.2021.12.003
- Dec 9, 2021
- Acta Biomaterialia
Transepithelial delivery of insulin conjugated with phospholipid-mimicking polymers via biomembrane fusion-mediated transcellular pathways
- Research Article
202
- 10.3390/pharmaceutics6020298
- Jun 17, 2014
- Pharmaceutics
Biocompatible clay materials have attracted particular attention as the efficient drug delivery systems (DDS). In this article, we review developments in the use of layered double hydroxides (LDHs) for controlled drug release and delivery. We show how advances in the ability to synthesize intercalated structures have a significant influence on the development of new applications of these materials. We also show how modification and/or functionalization can lead to new biotechnological and biomedical applications. This review highlights the most recent progresses in research on LDH-based controlled drug delivery systems, focusing mainly on: (i) DDS with cardiovascular drugs as guests; (ii) DDS with anti-inflammatory drugs as guests; and (iii) DDS with anti-cancer drugs as guests. Finally, future prospects for LDH-based drug carriers are also discussed.
- Research Article
20
- 10.1016/j.jddst.2023.104587
- Aug 1, 2023
- Journal of Drug Delivery Science and Technology
Recent advances in PLGA-based nanofibers as anticancer drug delivery systems
- Ask R Discovery
- Chat PDF