Nanosized Delivery Systems Research Articles

Double Encapsulation of Resveratrol and Doxorubicin in Composite Nanogel—An Opportunity to Reduce Cardio- and Neurotoxicity of Doxorubicin

The simultaneous encapsulation of drugs into nanosized delivery systems could be beneficial for cancer therapies since it could alleviate adverse reactions as well as provide synergistic effects. However, the encapsulation of hydrophobic drugs into hydrophilic nanoparticles, such as nanogels, could be challenging. Therefore, innovative technological approaches are needed. In this research, a composite nanogel system was prepared from chitosan, albumin, and hydroxypropyl-β-cyclodextrin for co-delivery of the hydrophilic anticancer drug doxorubicin and hydrophobic antioxidant resveratrol. The nanoparticles were characterized using dynamic light scattering and found to have a hydrodynamic diameter of approx. 31 nm, narrow size distribution (PDI = 0.188), positive ƺ-potential (+51.23 mV), and pH-dependent release of the loaded drugs. FTIR and X-ray analyses proved the successful development of the composite nanogel. Moreover, the double-loaded system showed that the loading of resveratrol exerted protection against doxorubicin-induced toxicity in cardioblast H9c2 and neuroblast SH-SY5Y cells. The simultaneous loading did not influence the cytostatic effect of the antitumor agent in lymphoma L5178Y and L5178MDR cell lines.

Bioactives in Nutricosmetics: A Focus on Caffeine from Tea to Coffee

Known for its stimulating effects on the nervous and cardiovascular systems, caffeine has proven remarkable versatile properties. It can be used in a wide range of different products, from anti-aging cosmetics to the pharmaceutical treatment of hair loss. Caffeine is known for its antioxidant properties and is commonly found in moisturising creams recommended as anti-aging or anti-cellulite and also for the treatment of different skin disorders, including androgenic alopecia. This bioactive is also described to be able to enhance the sunscreen scattering effect of well-known ultraviolet (UV) blockers. One of the major challenges remains its penetration capacity into deeper skin layers, which may be achieved by the use of nanosized delivery systems, yet without the risk of transdermal delivery. In this review, we discuss the nutraceutical value of caffeine in cosmetic products, so-called nutricosmetics, which grants this bioactive several advantages in several formulations, in comparison to other potential bioactives of nutricosmetic value. Furthermore, the disclosed effects of bioactives commonly found in coffee, tea, and their by-products are reviewed and discussed. The discussion concludes by highlighting the significant benefits of caffeine in the treatment of skin disorders and its potential to enhance and promote skin health.

Erythrocyte nano-ghosts with dual optical and magnetic resonance characteristics.

Fluorescent organic dyes provide imaging capabilities at cellular and sub-cellular levels. However, a common problem associated with some of the existing dyes such as the US FDA-approved indocyanine green (ICG) is their weak fluorescence emission. Alternative dyes with greater emission characteristics would be useful in various imaging applications. Complementing optical imaging, magnetic resonance (MR) imaging enables deep tissue imaging. Nano-sized delivery systems containing dyes with greater fluorescence emission as well as MR contrast agents present a promising dual-mode platform with high optical sensitivity and deep tissue imaging for image-guided surgical applications. We have engineered a nano-sized platform, derived from erythrocyte ghosts (EGs), with dual near-infrared fluorescence and MR characteristics by co-encapsulation of a brominated carbocyanine dye and gadobenate dimeglumine (Gd-BOPTA). We have investigated the use of three brominated carbocyanine dyes (referred to as BrCy106, BrCy111, and BrCy112) with various degrees of bromination, structural symmetry, and acidic modifications for encapsulation by nano-sized EGs (nEGs) and compared their resulting optical characteristics with nEGs containing ICG. We find that asymmetric dyes (BrCy106 and BrCy112) with one dibromobenzene ring offer greater fluorescence emission characteristics. For example, the relative fluorescence quantum yield ( ) for nEGs fabricated using of BrCy112 is -fold higher than nEGs fabricated using the same concentrations of ICG. The dual-mode nEGs containing BrCy112 and Gd-BOPTA show a nearly twofold increase in their as compared with their single optical mode counterpart. Cytotoxicity is not observed upon incubation of SKOV3 cells with nEGs containing BrCy112. Erythrocyte nano-ghosts with dual optical and MR characteristics may ultimately prove useful in various biomedical imaging applications such as image-guided tumor surgery where MR imaging can be used for tumor staging and mapping, and fluorescence imaging can help visualize small tumor nodules for resection.

Antibiotic-Loaded Nano-Sized Delivery Systems: An Insight into Gentamicin and Vancomycin.

The fight against infectious disease has remained an ever-evolving challenge in the landscape of healthcare. The ability of pathogens to develop resistance against conventional drug treatments has decreased the effectiveness of therapeutic interventions, and antibiotic resistance is recognized as one of the main challenges of our time. The goal of this systematic review paper is to provide insight into the research papers published on innovative nanosized drug delivery systems (DDSs) based on gentamycin and vancomycin and to discuss the opportunity of their repurposing through nano DDS formulations. These two antibiotics are selected because (i) gentamicin is the first-line drug used to treat suspected or confirmed infections caused by Gram-negative bacterial infections and (ii) vancomycin is used to treat serious Gram-positive bacterial infections. Moreover, both antibiotics have severe adverse effects, and one of the purposes of their formulation as nanosized DDSs is to overcome them. The review paper includes an introduction focusing on the challenges of infectious diseases and traditional therapeutic treatments, a brief description of the chemical and pharmacological properties of gentamicin and vancomycin, case studies from the literature on innovative nanosized DDSs as carriers of the two antibiotic drugs, and a discussion of the results found in the literature.

Poly(amino acid)-based drug delivery nanoparticles eliminate Methicillin resistant Staphylococcus aureus via tunable release of antibiotic

Bacterial infections threaten public health, and novel therapeutic strategies critically demand to be explored. Herein, poly(amino acid) (PAA)-based drug delivery nanoparticles (NPs) were designed for eliminating Methicillin resistant Staphylococcus aureus (MRSA) via tunable release of antibiotic. Using N-acryloyl amino acids (valine, valine methyl ester, aspartic acid, serine) as monomers, four kinds of amphiphilic PAAs were synthesized via photoinduced electron/energy transfer–reversible addition fragmentation chain-transfer (PET-RAFT) polymerization and were further assembled into nano-sized delivery systems. Their assemble behavior was drove mainly by hydrophobic/hydrophilic interaction, which determined the particle size, efficacy of drug loading and release; but numerous hydrogen bonding (HB) interaction also played an important role in regulating morphologies of the NPs and enriching drug-binding capacity. By changing the HB- and hydrophobic-interaction of the PAAs, the particle sizes (240.7 nm-302.7 nm), the drug loading efficiency (9.57%-19.76%), and the Rifampicin (Rif) release rate (49.6%-69.7%) of the PAA-based NPs could be tunable. Specially, the antimicrobial properties of the Rif-loaded NPs are found to be related to the release of Rif, which was determined by its hydrophobic interaction with hydrophobic blocks and HB interaction with hydrophilic blocks. These studies provide a new outlook for the design of delivery systems for the therapy of bacterial infection.

Impact of conjugation to different lipids on the lymphatic uptake and biodistribution of brush PEG polymers

Delivery to peripheral lymphatics can be achieved following interstitial administration of nano-sized delivery systems (nanoparticles, liposomes, dendrimers etc) or molecules that hitchhike on endogenous nano-sized carriers (such as albumin). The published work concerning the hitchhiking approach has mostly focussed on the lymphatic uptake of vaccines conjugated directly to albumin binding moieties (ABMs such as lipids, Evans blue dye derivatives or peptides) and their subsequent trafficking into draining lymph nodes. The mechanisms underpinning access and transport of these constructs into lymph fluid, including potential interaction with other endogenous nanocarriers such as lipoproteins, have largely been ignored. Recently, we described a series of brush polyethylene glycol (PEG) polymers containing end terminal short-chain or medium-chain hydrocarbon tails (1C2 or 1C12, respectively), cholesterol moiety (Cho), or medium-chain or long-chain diacylglycerols (2C12 or 2C18, respectively). We evaluated the association of these materials with albumin and lipoprotein in rat plasma, and their intravenous (IV) and subcutaneous (SC) pharmacokinetic profiles. Here we fully detail the association of this suite of polymers with albumin and lipoproteins in rat lymph, which is expected to facilitate lymph transport of the materials from the SC injection site. Additionally, we characterise the thoracic lymph uptake, tissue and lymph node biodistribution of the lipidated brush PEG polymers following SC administration to thoracic lymph cannulated rats. All polymers had moderate lymphatic uptake in rats following SC dosing with the lymph uptake higher for 1C2-PEG, 2C12-PEG and 2C18-PEG (5.8%, 5.9% and 6.7% dose in lymph, respectively) compared with 1C12-PEG and Cho-PEG (both 1.5% dose in lymph). The enhanced lymph uptake of 1C2-PEG, 2C12-PEG and 2C18-PEG appeared related to their association profile with different lipoproteins. The five polymers displayed different biodistribution patterns in major organs and tissues in mice. All polymers reached immune cells deep within the inguinal lymph nodes of mice following SC dosing. The ability to access these immune cells suggests the potential of the polymers as platforms for the delivery of vaccines and immunotherapies. Future studies will focus on evaluating the lymphatic targeting and therapeutic potential of drug or vaccine-loaded polymers in pre-clinical disease models.

A vivid outline demonstrating the benefits of exosome-mediated drug delivery in CNS-associated disease environments

The efficacy of drug delivery mechanisms has been improvised with time for different therapeutic purposes. In most cases, nano-sized delivery systems have been modeled over decades for the on-target applicability of the drugs. The use of synthetic drug delivery materials has been a common practice, although research has now focussed more on using natural vehicles, to avoid the side effects of synthetic delivery systems and easy acceptance by the body. Exosome is such a natural nano-sized vehicle that exceeds the efficiency of many natural vehicles, for being immune-friendly, due to its origin. Unlike, other natural drug delivery systems, exosomes are originated within the body's cells, and from there, they happen to travel through the extracellular matrices into neighboring cells. This capacity of exosomes has made them an efficient drug delivery system over recent years and now a large number of researches have been carried out to develop exosomes as natural drug delivery vehicles. Several experimental strategies have been practiced in this regard which have shown that exosomes are exclusively capable of carrying drugs and they can also be used in targeted delivery, for which they efficiently can reach and release the drug at their target cells for consecutive effects. One of the most interesting features of exosomes is they can cross the blood-brain barrier (BBB) in the body and hence, for the disease where other delivery vehicles are incapable of reaching the destination of the drug, exosomes can overcome the hurdle. This review particularly, focuses on the different aspects of using exosomes as a potential nano-sized drug delivery system for some of the severe diseases associated with the central nervous system of the human body.

Assessing the In Vitro Digestion of Lactoferrin-Curcumin Nanoparticles Using the Realistic Gastric Model.

Nanosized delivery systems have been the subject of research and discussion in the scientific community due to their unique properties and functionality. However, studies reporting the behaviour of nanodelivery systems under dynamic in vitro digestion conditions are still very scarce. To address this gap, this study aims to assess the dynamic in vitro gastric digestion of lactoferrin/curcumin nanoparticles in the realistic gastric model (RGM). For this purpose, the INFOGEST standard semi-dynamic digestion protocol was used. The nanosystems were characterized in terms of hydrodynamic size, size distribution, polydispersity index (PdI), and zeta potential using dynamic light scattering (DLS), before and during the digestion process. Confocal laser scanning microscopy (CLSM) was also used to examine particle aggregation. In addition, the release of curcumin was evaluated spectroscopically and the intrinsic fluorescence of lactoferrin was measured throughout the digestion process. The protein hydrolysis was also determined by UV-VIS-SWNIR spectroscopy to estimate, in real-time, the presence of free NH2 groups during gastric digestion. It was possible to observe that lactoferrin/curcumin nanoparticles were destabilized during the dynamic digestion process. It was also possible to conclude that low sample volumes can pose a major challenge in the application of dynamic in vitro digestion models.

Lipid-engineered nanotherapeutics for cancer management.

Cancer causes significant mortality and morbidity worldwide, but existing pharmacological treatments are greatly limited by the inherent heterogeneity of cancer as a disease, as well as the unsatisfactory efficacy and specificity of therapeutic drugs. Biopharmaceutical barriers such as low permeability and poor water solubility, along with the absence of active targeting capabilities, often result in suboptimal clinical results. The difficulty of successfully reaching and destroying tumor cells is also often compounded with undesirable impacts on healthy tissue, including off-target effects and high toxicity, which further impair the ability to effectively manage the disease and optimize patient outcomes. However, in the last few decades, the development of nanotherapeutics has allowed for the use of rational design in order to maximize therapeutic success. Advances in the fabrication of nano-sized delivery systems, coupled with a variety of surface engineering strategies to promote customization, have resulted in promising approaches for targeted, site-specific drug delivery with fewer unwanted effects and better therapeutic efficacy. These nano systems have been able to overcome some of the challenges of conventional drug delivery related to pharmacokinetics, biodistribution, and target specificity. In particular, lipid-based nanosystems have been extensively explored due to their high biocompatibility, versatility, and adaptability. Lipid-based approaches to cancer treatment are varied and diverse, including liposomal therapeutics, lipidic nanoemulsions, solid lipid nanoparticles, nanostructured lipidic carriers, lipid-polymer nanohybrids, and supramolecular nanolipidic structures. This review aims to provide an overview of the use of diverse formulations of lipid-engineered nanotherapeutics for cancer and current challenges in the field, as researchers attempt to successfully translate these approaches from bench to clinic.

Facile synthesis of AA'B- and ABC-type polypept(o)ide miktoarm star polymers utilizing polysarcosine end group functionalization for core introduction

Miktoarm star polymers display asymmetric architectures with combinations of multiple polymeric arms of different chemical nature emanating from a shared core. Their unique structure–property relationships in comparison to linear counterparts (with same molecular weight) make these architectures interesting for the design of novel polymeric species and the development of nanosized delivery systems. However, the synthesis of such structures is often demanding. Based on polypept(o)ides, we herein report on the synthesis of AA'B- and ABC-type miktoarm star polymers by introducing a multifunctional lysine end group to a polysarcosine (pSar) chain end, comprising orthogonal amine-protective groups. Therefore, each polymeric arm could be synthesized separately by living ring-opening polymerization (ROP) of respective N-carboxyanhydrides (NCAs), offering high reaction control and a resulting structure completely based on amino acids. We demonstrate the utility and versatility of this approach by designing a small, asymmetric and big AA'B miktoarm star polymer comprising two pSar arms with chain lengths of ∼50 or ∼150 in different combinations and a poly(Nε-trifluoroacetate-lysine) (pLys(TFA)) arm, as well as an ABC architecture by introducing a poly(γ-benzyl-glutamate) (pGlu(OBn)). 1H NMR, including 1H DOSY experiments, as well as size-exclusion chromatography (SEC) proof the successful and controlled synthesis of asymmetric miktoarm star polymers with precise control over degree of polymerization of the individual arms with narrow molecular weight distributions.

Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) as Food-Grade Nanovehicles for Hydrophobic Nutraceuticals or Bioactives

Although solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been successfully used as drug delivery systems for about 30 years, the usage of these nanoparticles as food-grade nanovehicles for nutraceuticals or bioactive compounds has been, relatively speaking, scarcely investigated. With fast-increasing interest in the incorporation of a wide range of bioactives in food formulations, as well as health awareness of consumers, there has been a renewed urge for the development of food-compatible SLNs and/or NLCs as nanovehicles for improving water dispersibility, stability, bioavailability, and bioactivities of many lipophilic nutraceuticals or poorly soluble bioactives. In this review, the development of food-grade SLNs and NLCs, as well as their utilization as nanosized delivery systems for lipophilic or hydrophobic nutraceuticals, was comprehensively reviewed. First, the structural composition and preparation methods of food-grade SLNs and NLCs were simply summarized. Next, some key issues about the usage of such nanoparticles as oral nanovehicles, e.g., incorporation and release of bioactives, oxidative stability, lipid digestion and absorption, and intestinal transport, were critically discussed. Then, recent advances in the utilization of SLNs and NLCs as nanovehicles for encapsulation and delivery of different liposoluble or poorly soluble nutraceuticals or bioactives were comprehensively reviewed. The performance of such nanoparticles as nanovehicles for improving stability, bioavailability, and bioactivities of curcuminoids (and curcumin in particular) was also highlighted. Lastly, some strategies to improve the oral bioavailability and delivery of loaded nutraceuticals in such nanoparticles were presented. The review will be relevant, providing state-of-the-art knowledge about the development of food-grade lipid-based nanovehicles for improving the stability and bioavailability of many nutraceuticals.

Development of potent nanosized carbonic anhydrase inhibitor for targeted therapy of hypoxic solid tumors

Overexpression of two carbonic anhydrase (CA) isoforms, CA IX and XII, in several hypoxic solid tumors provides an extracellular hypoxic microenvironment, interferes with extra- and intracellular pH regulation, thus favoring hypoxic tumor cell survival, proliferation and metastasis. In the current study, a selective inhibitor for human CA isoforms IX and XII (isatin-bearing sulfonamide, WEG-104), was incorporated into nanosized spherical niosomes at high encapsulation efficiency to allow for an enhanced and sustained antitumor activity. In vivo, administration of WEG-104 that is either free (10 mg/kg) or loaded into niosomes (5 mg/kg) into a mice model of Ehrlich ascites solid tumor resulted in comparable efficacy in terms of reduction of tumor weight and volume. Administration of WEG-104-loaded niosomes (10 mg/kg) exhibited superior antitumor activity compared to the free drug, evidenced by reduced tumor weight and volume, marked reduction in the activity of CA IX and XII, and suppression of HIF-1α and MMP-2. Moreover, prominent increase of caspase 3 and pronounced decrease in VEGF immune expression were observed in the treated animals. Hence, loading of molecularly designed compounds that targets CAs in hypoxic solid tumors into nanosized delivery systems provided an auspicious strategy for limiting solid tumor progression and malignancy.

Tobramycin Nanoantibiotics and Their Advantages: A Minireview.

Nowadays, antimicrobial resistance (AMR) represents a challenge for antibiotic therapy, mostly involving Gram-negative bacteria. Among the strategies activated to overcome AMR, the repurposing of already available antimicrobial molecules by encapsulating them in drug delivery systems, such as nanoparticles (NPs) and also engineered NPs, seems to be promising. Tobramycin is a powerful and effective aminoglycoside, approved for complicated infections and reinfections and indicated mainly against Gram-negative bacteria, such as Pseudomonas aeruginosa, Escherichia coli, Proteus, Klebsiella, Enterobacter, Serratia, Providencia, and Citrobacter species. However, the drug presents several side effects, mostly due to dose frequency, and for this reason, it is a good candidate for nanomedicine formulation. This review paper is focused on what has been conducted in the last 20 years for the development of Tobramycin nanosized delivery systems (nanoantibiotics), with critical discussion and comparison. Tobramycin was selected as the antimicrobial drug because it is a wide-spectrum antibiotic that is effective against both Gram-positive and Gram-negative aerobic bacteria, and it is characterized by a fast bactericidal effect, even against multidrug-resistant microorganisms (MDR).

Zein-based nano-delivery systems for encapsulation and protection of hydrophobic bioactives: A review.

Zein is a kind of excellent carrier materials to construct nano-sized delivery systems for hydrophobic bioactives, owing to its unique interfacial behavior, such as self-assembly and packing into nanoparticles. In this article, the chemical basis and preparation methods of zein nanoparticles are firstly reviewed, including chemical crosslinking, emulsification/solvent evaporation, antisolvent, pH-driven method, etc., as well as the pros and cons of different preparation methods. Various strategies to improve their physicochemical properties are then summarized. Lastly, the encapsulation and protection effects of zein-based nano-sized delivery systems (e.g., nanoparticles, nanofibers, nanomicelles and nanogels) are discussed, using curcumin as a model bioactive ingredient. This review will provide guidance for the in-depth development of hydrophobic bioactives formulations and improve the application value of zein in the food industry.

IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery.

The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000′s, resulted in the creation of a Coordinated Research Project (CRP) by the International Atomic Energy Agency (IAEA) in 2014. This CRP entitled ‘Nanosized delivery systems for radiopharmaceuticals’ involved a team of expert scientist from various member states. This team of scientists worked on a number of cutting-edge areas of nanoscience with a focus on developing well-defined, highly effective and site-specific delivery systems of radiopharmaceuticals. Specifically, focus areas of various teams of scientists comprised of the development of nanoparticles (NPs) based on metals, polymers, and gels, and their conjugation/encapsulation or decoration with various tumor avid ligands such as peptides, folates, and small molecule phytochemicals. The research and development efforts also comprised of developing optimum radiolabeling methods of various nano vectors using diagnostic and therapeutic radionuclides including Tc-99m, Ga-68, Lu-177 and Au-198. Concerted efforts of teams of scientists within this CRP has resulted in the development of various protocols and guidelines on delivery systems of nanoradiopharmaceuticals, training of numerous graduate students/post-doctoral fellows and publications in peer reviewed journals while establishing numerous productive scientific networks in various participating member states. Some of the innovative nanoconstructs were chosen for further preclinical applications—all aimed at ultimate clinical translation for treating human cancer patients. This review article summarizes outcomes of this major international scientific endeavor.

Contribution of Nanoscience Research in Antioxidants Delivery Used in Nutricosmetic Sector.

Nanoscience applications in the food and cosmetic industry offer many potential benefits for consumers and society. Nanotechnologies permit the manipulation of matter at the nanoscale level, resulting in new properties and characteristics useful in food and cosmetic production, processing, packaging, and storage. Nanotechnology protects sensitive bioactive compounds, improves their bioavailability and water solubility, guarantees their release at a site of action, avoids contact with other constituents, and masks unpleasant taste. Biopolymeric nanoparticles, nanofibers, nanoemulsions, nanocapsules, and colloids are delivery systems used to produce food supplements and cosmetics. There are no barriers to nanoscience applications in food supplements and cosmetic industries, although the toxicity of nano-sized delivery systems is not clear. The physicochemical and toxicological characterization of nanoscale delivery systems used by the nutricosmeceutic industry is reviewed in this work.

Stealth doxorubicin conjugated bimetallic selenium/silver nanoparticles for targeted cervical cancer therapy

Bimetallic nanosized delivery systems are attracting a lot of research interest as alternatives to monometallic delivery systems. This study evaluated the ability of bimetallic selenium silver chitosan pegylated folic acid targeted nanoparticles (SeAgChPEGFA NPs) to deliver doxorubicin (DOX) in cervical cancer cells. Comparison studies using monometallic selenium chitosan pegylated folic acid (SeChPEGFA NPs) targeted NPs and free DOX were also conducted. The prepared NPs and their drug nanocomplexes were characterised morphologically and physico-chemically. Drug binding and releasing studies were conducted under a simulated environment in vitro. The cytotoxicity and apoptosis studies were studied using the 3-[(4, 5-dimethylthiazol-2-yl)−2, 5-diphenyl tetrazolium bromide] (MTT) assay and the dual dye staining. The findings revealed that the bimetallic SeAgChPEGFA NPs displayed better colloidal stability, superior physico-chemical qualities, and higher binding abilities in comparison with monometallic SeChPEGFA NPs. In addition, the SeAgChPEGFA NPs showed the pH-triggered controlled drug release and cell-specific cytotoxicity. These findings suggest that the bimetallic NPs are superior delivery systems when compared to their monometallic NPs and free drug counterparts, thus, setting a platform for further in vivo examination.

Extraction and Nano-Sized Delivery Systems for Phlorotannins to Improve Its Bioavailability and Bioactivity.

This review aims to provide an informative summary of studies on extraction and nanoencapsulation of phlorotannins to improve their bioavailability and bioactivity. The origin, structure, and different types of phlorotannins were briefly discussed, and the extraction/purification/characterization methods for phlorotannins were reviewed, with a focus on techniques to improve the bioactivities and bioavailability of phlorotannins via nano-sized delivery systems. Phlorotannins are promising natural polyphenol compounds that have displayed high bioactivities in several areas: anticancer, anti-inflammation, anti-HIV, antidiabetic, and antioxidant. This review aims to provide a useful reference for researchers working on developing better utilization strategies for phlorotannins as pharmaceuticals, therapeuticals, and functional food supplements.

Experimental and computational insight of the supramolecular complexes of Irbesartan with β-cyclodextrin based nanosponges

Irbesartan (IRB), one of the extensively prescribed drugs, for treatment of hypertension has limited therapeutic potential attributed to its poor water solubility, slow dissolution rate and poor bioavailability. Cyclodextrin-based nanosponges (NSs) are novel nanosized delivery systems comprised of hyper-crosslinked solid nanoparticles with nanosized cavities. Nanosponges are widely explored to increase water solubility of active drug moieties, to protect labile actives, to achieve prolonged or sustained release and site-specific targeting. The aim of the study was to investigate enhancement of solubility of Irbesartan by its complexation with β-cyclodextrin (β–CD) based nanosponges (NS). Blank NSs were fabricated by reacting β–CD, with pyromellitic dianhydride (PMDA) and diphenyl carbonate (DPC) as cross linkers, in various molar ratios of 1:2, 1:4, 1:6 and 1:8. Solubility studies were performed to select drug nanosponge stoichiometric complex with highest degree of saturation solubilization. Irbesartan loaded nanosponges namely PMDA-CDNS and DPC–CDNS were prepared and characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, powdered X-ray diffraction, scanning electron microscopy and nuclear magnetic resonance studies, to confirm the complexation of Irbesartan with nanosponges. PXRD studies revealed the shift from crystalline nature of Irbesartan to amorphous form in nanoponges. The average particle sizes of IRB–PMDA-CDNS and IRB-DPC-CDNS were 471.5 nm and 382.7 nm respectively. Zeta Potential values were 34.9 mV and −29mV for IRB–PMDA-CDNS and IRB- DPC-CDNS respectively. Entrapment efficiency varied from 9 to 38% w/w and 17 to 33%w/w for IRB–PMDA-CDNS and IRB-DPC-CDNS respectively. Complexation of IRB with β-cyclodextrin based nanosponges, as IRB-PMDA-CDNS and IRB-DPC-CDNS, resulted in significant enhancement of 81.86 and 23.35 folds, in its water solubility and 1.91- and 1.96-folds enhancement in its percent dissolution efficiency (% D.E.) respectively. Molecular docking calculations of IRB with DPC-CDNS and PMDA-CDNS have exhibited binding affinities of −8.97 and −9.51 kcal/mol respectively. Molecular dynamics simulations have revealed that IRB with PMDA-CDNS is more stable and efficient nanocarrier.

Biomimetic nanoarchitecturing: A disguised attack on cancer cells

With the changing face of healthcare, there is a demand for drug delivery systems that have increased efficacy and biocompatibility. Nanotechnology derived drug carrier systems were found to be ideal candidates to meet these demands. Among the vast number of nanosized delivery systems, biomimetic nanoparticles have been researched at length. These nanoparticles mimic cellular functions and are highly biocompatible. They are also able to avoid clearance by the reticuloendothelial system which increases the time spent by them in the systemic circulation. Additionally, their low immunogenicity and targeting ability increase their significance as drug carriers. Based on their core material we have summarized them as biomimetic inorganic nanoparticles, biomimetic polymeric nanoparticles, and biomimetic lipid nanoparticles. The core then may be coated using membranes derived from erythrocytes, cancer cells, leukocytes, stem cells, and other membranes to endow them with biomimetic properties. They can be used for personalized therapy and diagnosis of a large number of diseases, primarily cancer. This review summarizes the various therapeutic approaches using biomimetic nanoparticles along with their applications in the field of cancer imaging, nucleic acid therapy and theranostic properties. A brief overview about toxicity concerns related to these nanoconstructs has been added to provide knowledge about biocompatibility of such nanoparticles.