Drug Nanoformulations Research Articles

An endophytic fungus, Penicillium simplicissimum conjugated with C60 fullerene for its potential antimitotic, anti-inflammatory, anticancer and photodegradation activities

ABSTRACT In the present study, endophytic fungus, Penicillium simplicissimum isolated from Loranthus micranthus was used to analyze phytochemical studies by qualitative and GC-MS methods. The endophytic fungus P. simplicissimum yielded novel compound penisimplicissin identified through GC-MS studies. Further, P. simplicissimum was conjugated with C60 fullerene nanoparticles (Ps-FNPs) were verified using UV-vis spectra, XRD, FTIR, DLS, EDX and SEM. Ps-FNPs was confirmed using UV-visible spectra with a peak at 260 nm. The IR bands were recorded at 2085, 1428, 1181, 661, 652, 644, 628, and 604 cm-1. The Ps-FNPs treated cells showed a nucleolar shrinkage and cell arrest atprophase, binuclear and multinucleolar cells, a chromosomal bridge and diversion at anaphase was observed, whereas, chromosomal fragment and abnormal distribution at metaphase stage. The Ps-FNPs exhibited a noteworthy anticancer activity on lung cancer cell line H1975 through cytotoxicity. The cytotoxicity was induced by increasing caspase-3, 7, and 9 activities and also showed highest inhibition in xanthine oxidase and COX-II assay proved good anti-inflammatory activity. Ps-FNPs have been extensively studied for photocatalytic activity test against Rhodamine B, Methylene blue and nigrosine showed potential dye degradation in the presence of sunlight proved to be novel photocatalysts. With all the results recorded, Ps-FNPs also have a synergetic effect having on anti-mitotic, anticancer, anti-inflammation potential and photocatalytic degradation of dyes. Hence, the conjugated Ps-FNPs could be one of the potent nano-drug formulations in future. Thus, the present study gives a clear idea of the multifaceted therapeutic and photocatalytic applications.

Dendrimeric nanosystem consistently circumvents heterogeneous drug response and resistance in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with no efficacious treatment. The application of nanomedicine is expected to bring new hope to PDAC treatment. In this study, we report a novel supramolecular dendrimeric nanosystem carrying the anticancer drug doxorubicin, which demonstrated potent anticancer activity, markedly overcoming the heterogeneity of drug response and resistance of primary cultured tumor cells derived from PDAC patients. This dendrimer nanodrug was constructed with a fluorinated amphiphilic dendrimer, which self-assembled into micelles nanostructure and encapsulated doxorubicin with high loading. Because of the fine nanosize, stable formulation and acid-promoted drug release, this dendrimeric nanosystem effectively accumulated in tumor, with deep penetration in tumor tissue and rapid drug uptake/release profile in cells, ultimately resulting in potent anticancer activity and complete suppression of tumor growth in patient-derived xenografts. Most importantly, this dendrimer nanodrug generated uniform and effective response when treating 35 primary pancreatic cancer cell lines issued from patient samples as a robust platform for preclinical drug efficacy testing. In addition, this dendrimer nanodrug formulation was devoid of adverse effects and showed excellent tolerability. Given all these uniquely advantageous features, this simple and convenient dendrimer nanodrug holds great promise as a potential candidate to treat the deadly PDAC.

Nanoparticles and nanoformulated drugs as promising delivery system in treatment of microbial-induced CNS infection: a systematic review of literature.

Central nervous system (CNS) infection is a global health problem with high rate of mortality and associated morbidities. Viruses, bacteria, fungi, and protozoa parasites are the main cause of CNS infection. Various medications are currently used for treatment of brain infections, but most of them do not have enough efficiency because the majority of conventional drugs cannot pass the blood-brain barrier (BBB) to combat the pathogens. Nanotechnology has provided promising approaches to solve this issue, since nanoparticles (NPs) can facilitate the drugs entrance through the BBB. Herein, we systematically reviewed all available literature to provide evidences for practicality of NPs in treatment of CNS infection. A systematic literature search was performed on January 29, 2021, in Web of Science, PubMed, Scopus, Science Direct, Embase, Ovid, and Google Scholar using "CNS infections" and "NPs/nanoformulation" including all their equivalent terms as keyword. Due to lack of human studies, no strict inclusion criteria were defined, and all relevant documents were included. After several steps of article selection, a total of 29 documents were collected and used for data synthesis. The results showed that drug-loaded NPs is fairly safe and can be a promising approach in developing anti-infective agents for treatment of CNS infection, since nanoformulated drugs could act up to tenfold more efficient that drug alone. Findings of this review indicate the importance of NPs and nanoformulation of drugs to enhance the efficiency of treatment and warrant the safety of treatment in human studies; however, clinical trials are required to confirm such efficiency and safety in clinical practice.

Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics.

The smart strategy of cancer cells to bypass the caspase-dependent apoptotic pathway has led to the discovery of novel anti-cancer approaches including the targeting of lysosomes. Recent discoveries observed that lysosomes perform far beyond just recycling of cellular waste, as these organelles are metabolically very active and mediate several signalling pathways to sense the cellular metabolic status. These organelles also play a significant role in mediating the immune system functions. Thus, direct or indirect lysosome-targeting with different drugs can be considered a novel therapeutic approach in different disease including cancer. Recently, some anticancer lysosomotropic drugs (eg, nortriptyline, siramesine, desipramine) and their nanoformulations have been engineered to specifically accumulate within these organelles. These drugs can enhance lysosome membrane permeabilization (LMP) or disrupt the activity of resident enzymes and protein complexes, like v-ATPase and mTORC1. Other anticancer drugs like doxorubicin, quinacrine, chloroquine and DQ661 have also been used which act through multi-target points. In addition, autophagy inhibitors, ferroptosis inducers and fluorescent probes have also been used as novel theranostic agents. Several lysosome-specific drug nanoformulations like mixed charge and peptide conjugated gold nanoparticles (AuNPs), Au-ZnO hybrid NPs, TPP-PEG-biotin NPs, octadecyl-rhodamine-B and cationic liposomes, etc. have been synthesized by diverse methods. These nanoformulations can target cathepsins, glucose-regulated protein 78, or other lysosome specific proteins in different cancers. The specific targeting of cancer cell lysosomes with drug nanoformulations is quite recent and faces tremendous challenges like toxicity concerns to normal tissues, which may be resolved in future research. The anticancer applications of these nanoformulations have led them up to various stages of clinical trials. Here in this review article, we present the recent updates about the lysosome ultrastructure, its cross-talk with other organelles, and the novel strategies of targeting this organelle in tumor cells as a recent innovative approach of cancer management.

Nanoformulations of Drugs Based on Biodegradable Lactide Copolymers with Various Molecular Structures and Architectures

Modern pharmaceutics are actively developing towards the design of targeted drugs. The development of selectively acting formulations requires the creation of smart delivery systems based on carriers that would first find the target cells and enter them and then release the active substance locally. Nanoparticles of biocompatible and biodegradable polymers can be effectively used as such carriers. Flexible regulation of the molecular structure and architecture of polymers, as well as the modification of nanoparticles with vector molecules, allows one to construct carrier particles for the development of nanoformulations for active agents of various nature. This review presents the main approaches to the design of nanoformulations for targeted delivery, describes the methods for the preparation and study of nanoparticles based on hydrophobic and amphiphilic biodegradable lactide polymers, and discusses the effect of the molecular structure and preparation conditions on the characteristics of nanoparticles in detail. Some results of research in this area of the Kurchatov complex of NBIСS nature-like technologies are also presented.

Giemsa Staining of Some Nano-formulations on Neuroblastoma Cell Line

Background: Nano-formulations of various drugs and natural compounds are becoming popular day by day. A number of cosmetic, medicinal and herbal products are formulated using nano-carriers. However, one of the concerns using these carriers is the alteration in morphology of cell by using such particles or droplets. Methods: In the present work, Giemsa staining was used to study the morphological changes on mammalian Neuro-2a cell line upon treatment with prepared capsaicin loaded nanoemulsion (Caps-NE), baclofen loaded poly(lactic-co-glycolic acid) nanoparticles (Bcf-PLGA-NPs) and lamotrigine loaded poly(lactic-co-glycolic acid) nanoparticles (Ltg-PLGA-NPs). Caps-NE, Bcf- PLGA-NPs and Ltg-PLGA-NPs, along with their respective aqueous drug counterparts, were examined for visible morphological changes at their corresponding reported maximum plasma concentration (Cmax) and 10xCmax values. Results: Microscopic images showed that drug loaded nanoemulsion/nanoparticles showed comparable cell viability and exhibited lesser cytotoxicity than the available aqueous drug forms at both the concentrations. Conclusion: The prepared formulations can be used as potentially safer option as compared to their aqueous counterparts.

Self-Activating Therapeutic Nanoparticle: A Targeted Tumor Therapy Using Reactive Oxygen Species Self-Generation and Switch-on Drug Release.

One of the recent advances in nanotechnology within the medical field is the development of a nanoformulation of anticancer drugs or photosensitizers. Cancer cell-specific drug delivery and upregulation of the endogenous level of reactive oxygen species (ROS) are important in precision anticancer treatment. Within our article, we report a new therapeutic nanoformulation of cancer cell targeting using endogenous ROS self-generation without an external initiator and a switch-on drug release (ROS-induced cascade nanoparticle degradation and anticancer drug generation). We found a substantial cellular ROS generation by treating an isothiocyanate-containing chemical and functionalizing it onto the surface of porous silicon nanoparticles (pSiNPs) that are biodegradable and ROS-responsive nanocarriers. Simultaneously, we loaded an ROS-responsive prodrug (JS-11) that could be converted to the original anticancer drug, SN-38, and conducted further surface functionalization with a cancer-targeting peptide, CGKRK. We demonstrated the feasibility as a cancer-targeting and self-activating therapeutic nanoparticle in a pancreatic cancer xenograft mouse model, and it showed a superior therapeutic efficacy through ROS-induced therapy and drug-induced cell death. The work presented is a new concept of a nanotherapeutic and provides a more feasible clinical translational pathway.

Organoids: A new approach in toxicity testing of nanotherapeutics.

Nanotechnology has revolutionized diverse fields, which include agriculture, the consumer market, medicine, and other fields. Widespread use of nanotechnology-based products has led to increased prevalence of these novel formulations in the environment, which has raised concerns regarding their deleterious effects. The application of nanotechnology-based formulations into clinical use is hampered by the lack of the availability of effective in vitro systems, which could accurately assess their in vivo toxic effects. A plethora of studies has shown the hazardous effects of nanoparticle-based formulations in two-dimensional in vitro cell cultures and animal models. These have some associated disadvantages when used for the evaluation of nano-toxicity. Organoid technology fills the space between existing two-dimensional cell line culture and in vivo models. The uniqueness of organoids over other systems for evaluating toxicity caused by nano-drug formulation includes them being a co-culture of diverse cell types, dynamic flow within them that simulates the actual flow of nanoparticles within biological systems, extensive cell-cell, cell-matrix interactions, and a tissue-like morphology. Thus, it mimics the actual tissue microenvironment and, subsequently, provides an opportunity to study drug metabolism and toxico-dynamics of nanotechnology-based novel formulations. The use of organoids in the evaluation of nano-drug toxicity is in its infancy. A limited number of studies conducted so far have shown good predictive value and efficiently significant data correlation with the clinical trials. In this review, we attempt to introduce organoids of the liver, lungs, brain, kidney intestine, and potential applications to evaluate toxicity caused by nanoparticles.

Magnetic Nanoparticles In Hyperthermia Therapy: A Mini-Review

The activation of MNPs for hyperthermia therapy via an external alternating magnetic field is an interesting method in targeted cancer therapy. This mini-review explains new developments and implications of magnetic nanofluids mediated magnetic hyperthermia for their potential use in future clinical settings. The external alternating magnetic field generates heat in the tumor area to eliminate cancer cells. Depending on the tumor type and targeted area, several kinds of MNPs with different coating agents of various morphology and surface charge have been developed. The tunable physiochemical characteristics of MNPs enhance their heating capability. In addition, heating efficiency is strongly associated with the amount of the applied magnetic field and frequency. The great efforts have offered promising preclinical trials of magnetic hyperthermia via MNPs as a smart nanoagent. MNPs are very appropriate to be considered as a heating source in MHT and prospective research in this field will lead to tackle the problems from chemotherapy and introduce promising therapeutic techniques and nanodrug formulations for remotely controlled drug release and anticancer effects. This mini-review aims to pinpoint synthesis and structural analysis of various magnetic nanoparticles examined for magnetic hyperthermia therapy and controlled drug release in cancer treatment.

Computationally guided high-throughput design of self-assembling drug nanoparticles.

Nanoformulations of therapeutic drugs are transforming our ability to effectively deliver and treat a myriad of conditions. Often, however, they are complex to produce and exhibit low drug loading, except for nanoparticles formed via co-assembly of drugs and small molecular dyes, which display drug loading capacities of up to 95%. There is currently no understanding of which of the millions of small molecule combinations can result in the formation of these nanoparticles. Here, we report the integration of machine learning with high-throughput experimentation to enable the rapid and large-scale identification of such nanoformulations. We identified 100 self-assembling drug nanoparticles from 2.1 million pairings, each including one of 788 candidate drugs and one of 2686 approved excipients. We further characterized two nanoparticles, sorafenib-glycyrrhizin and terbinafine-taurocholic acid, both ex vivo and in vivo. We anticipate that our platform can accelerate the development of safer and more efficacious nanoformulations with high drug loading capacities for a wide range of therapeutics.

2D MXenes with antiviral and immunomodulatory properties: A pilot study against SARS-CoV-2.

Two-dimensional transition metal carbides/carbonitrides known as MXenes are rapidly growing as multimodal nanoplatforms in biomedicine. Here, taking SARS-CoV-2 as a model, we explored the antiviral properties and immune-profile of a large panel of four highly stable and well-characterized MXenes - Ti3C2Tx, Ta4C3T x , Mo2Ti2C3T x and Nb4C3T x . To start with antiviral assessment, we first selected and deeply analyzed four different SARS-CoV-2 genotypes, common in most countries and carrying the wild type or mutated spike protein. When inhibition of the viral infection was tested in vitro with four viral clades, Ti3C2T x in particular, was able to significantly reduce infection only in SARS-CoV-2/clade GR infected Vero E6 cells. This difference in the antiviral activity, among the four viral particles tested, highlights the importance of considering the viral genotypes and mutations while testing antiviral activity of potential drugs and nanomaterials. Among the other MXenes tested, Mo2Ti2C3T x also showed antiviral properties. Proteomic, functional annotation analysis and comparison to the already published SARS-CoV-2 protein interaction map revealed that MXene-treatment exerts specific inhibitory mechanisms. Envisaging future antiviral MXene-based drug nano-formulations and considering the central importance of the immune response to viral infections, the immune impact of MXenes was evaluated on human primary immune cells by flow cytometry and single-cell mass cytometry on 17 distinct immune subpopulations. Moreover, 40 secreted cytokines were analyzed by Luminex technology. MXene immune profiling revealed i) the excellent bio and immune compatibility of the material, as well as the ability of MXene ii) to inhibit monocytes and iii) to reduce the release of pro-inflammatory cytokines, suggesting an anti-inflammatory effect elicited by MXene. We here report a selection of MXenes and viral SARS-CoV-2 genotypes/mutations, a series of the computational, structural and molecular data depicting deeply the SARS-CoV-2 mechanism of inhibition, as well as high dimensional single-cell immune-MXene profiling. Taken together, our results provide a compendium of knowledge for new developments of MXene-based multi-functioning nanosystems as antivirals and immune-modulators.

Implementation of Analytical Quality-by-Design for Developing a Robust HPLC Method for Quantitative Estimation of Voriconazole: Application in Drug Formulations

The current studies endeavour to develop and validate a simple, sensitive and robust reversed- phase (RP) high-performance liquid chromatography (HPLC) methodology for quantitative estimation of voriconazole (VRC), following systematic principles of Analytical Quality-by-Design (AQbD). A comprehensive risk assessment plan, followed by factor screening studies employing Taguchi design, was executed to select “vital few” critical method parameters, influencing critical analytical attributes. Subsequently, response surface optimisation studies were conducted on the identified critical method parameters, viz., mobile phase ratio and flow rate, with chosen critical analytical attributes, viz., peak area, theoretical plate count, retention time and peak tailing, employing a Central Composite Design. The design space, demarcating the optimal method operating conditions, was identified using graphical optimisation and subsequently validated employing Monte Carlo simulations. The optimal solution consisted of acetonitrile and acetic acid solution (0.05 %, pH 4) as mobile phase (50:50 v/v), flow rate of 1 mL/ min with a detection wavelength of 256 nm, exhibiting linearity between 0.1 and 50 μg/mL in methanol and Hanks balanced salt solution. Validation studies confirmed precision (97.78-103.42 %), accuracy (98.99-102.34 %), and suitability of the developed analytical method for effective quantification of VRC with high sensitivity (LOD: 0.031 μg/mL; LOQ: 0.093 μg/mL). The validated analytical technique was successfully ratified for quantification of VRC in drug nanoformulations too. In a nutshell, the application of AQbD and Monte Carlo simulations aided in developing a robust analytical method for the estimation of VRC per se as well as in drug nanoformulations.

Abstract PS18-24: Impact of protein corona formation on Fn14-targeted DART nanoparticle selectivity, uptake, and cytotoxicity on TNBC cells

Abstract Despite dramatic improvements in the treatment of primary breast cancers, there currently are no effective targeted therapeutics for women diagnosed with metastatic triple negative breast cancer (mTNBC), resulting in an overall survival of just ~13 months in these patients. Drug-loaded nanoparticles (NPs) offer the potential to improve the therapeutic efficacy and pharmacokinetic profile of drugs through use of passive and active targeting to metastatic tumors. However, effective and active targeting of nanodrug formulations to tumor cells is complicated by the adsorption of proteins to NP surfaces upon exposure to the systemic circulation. Termed ‘protein coronas’, this protein coat can drastically reduce the blood circulation time and targeting capability of NPs in vivo. We have developed paclitaxel (PTX)-loaded NPs that are engineered for decreased non-specific adhesivity and receptor-targeting (‘DART’) characteristics, which balance minimal recognition by circulating immune cells and low non-specific binding to tumor extracellular matrix proteins with maximal targeting to tumor tissues. These DARTs selectively bind the fibroblast growth factor-inducible 14 (Fn14) cell surface receptor, which is overexpressed in over a dozen solid cancers and their metastases, including mTNBC tumors. We recently demonstrated the enhanced therapeutic efficacy of Fn14-targeted DARTs in comparison to a non-targeted nanoformulation and Abraxane, an FDA-approved nanoformulation for mTNBC, in xenograft models of primary and intracranial TNBC. In addition, we found that these DARTs retain targeting capability and traffic to Fn14+ tumors in the presence of an endogenous protein corona in vitro and in vivo. This encouraged further investigation into the specific mechanisms of DART NP uptake in tumor cells in both the presence and absence of protein coronas using surface plasmon resonance, flow cytometry, total internal reflection fluorescence and confocal microscopy, and cytotoxicity assays. Understanding the role of protein coronas on this drug delivery platform is crucial for its clinical development and these results provide valuable new information pertaining to the optimization of NP surface properties for minimizing the impact of protein coronas and improving mTNBC tumor targeting in vivo. Citation Format: Christine P Carney, Anshika Kapur, Nikhil Pandey, Jimena G Dancy, Aniket S Wadajkar, Graeme F Woodworth, Jeffrey A Winkles, Anthony J Kim. Impact of protein corona formation on Fn14-targeted DART nanoparticle selectivity, uptake, and cytotoxicity on TNBC cells [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-24.

α3 integrin-binding peptide-functionalized polymersomes loaded with volasertib for dually-targeted molecular therapy for ovarian cancer

Ovarian cancer (OC) is a high-mortality malignancy in women with a five-year survival rate of 30-40%. There is an urgent need to develop high-efficacy and low toxic treatments for OC. Herein, we report an appealing strategy that combines α3 integrin targeted polymersomes (A3-Ps) and targeted molecular drug, polo-like kinase 1 (PLK1) inhibitor volasertib (Vol) for dually targeted molecular therapy of OC in vivo. A3-Ps had good Vol loading of 7.7-8.0 wt.% and small size of 25-32 nm, depending on the density of α3 integrin binding peptide A3. Interestingly, cellular uptake studies using FITC-labeled Vol revealed that A3-Ps with 20% peptide gave 2.3 and 3.3-fold better internalization in SKOV-3 OC cells compared with non-targeted Ps and free Vol, respectively. Accordingly, Vol loaded in A3-Ps showed the best inhibitory activity to SKOV-3 cells with an IC50 of 49 nM, which was 3.5 times lower than free Vol. Importantly, the in vivo experiments demonstrated that A3-Ps-Vol proficiently repressed the growth of SKOV-3 tumors in mice while continuous tumor growth was observed for Ps-Vol and free Vol-treated mice. A3-Ps-Vol besides boosting anti-OC activity also reduced the systemic toxicity of Vol. This dually targeted molecular drug nanoformulation has appeared to be an especially potent and low toxic treatment modality for human ovarian cancers. Statement of significanceVolasertib provides a potential molecular therapy for PLK1-positive advanced OC patients. The initial clinical outcomes, nevertheless, showed a suboptimal efficacy, possibly resulting from its fast clearance, deficient tumor deposition and dose-limiting toxicities. Here, we show for the first time that dually targeted molecular therapy of OC using α3 integrin-binding peptide-modified polymersomes as a vehicle gives markedly improved potency, better toleration, and depleted adverse effects in SKOV-3 tumor models, greatly outperforming free volasertib. This dually targeted strategy has emerged as an appealing treatment for malignant PLK1-positive ovarian tumors.

Poly(2-oxazoline)- and Poly(2-oxazine)-Based Self-Assemblies, Polyplexes, and Drug Nanoformulations-An Update.

For many decades, poly(2-oxazoline)s and poly(2-oxazine)s, two closely related families of polymers, have led the life of a rather obscure research topic with only a few research groups world-wide working with them. This has changed in the last five to ten years, presumably triggered significantly by very promising clinical trials of the first poly(2-oxazoline)-based drug conjugate. The huge chemical and structural toolbox poly(2-oxazoline)s and poly(2-oxazine)s has been extended very significantly in the last few years, but their potential still remains largely untapped. Here, specifically, the developments in macromolecular self-assemblies and non-covalent drug delivery systems such as polyplexes and drug nanoformulations based on poly(2-oxazoline)s and poly(2-oxazine)s are reviewed. This highly dynamic field benefits particularly from the extensive synthetic toolbox poly(2-oxazoline)s and poly(2-oxazine)s offer and also may have the largest potential for a further development. It is expected that the research dynamics will remain high in the next few years, particularly as more about the safety and therapeutic potential of poly(2-oxazoline)s and poly(2-oxazine)s is learned.

Combined Delivery of DOX and Kaempferol using PEGylated Gold Nanoparticles to Target Colon Cancer

Recent treatments for malignant colon cancer in clinics are not efficacious and often result in deprived patient compliance due to short therapeutic efficacy and sturdy systemic side effects. To overcome this issue in the present study, we designed and formulated nanomaterial (PEGylated AuNPs-DOX@Kaempferol) for drug delivery system against colon cancer. The drug release behavior was subsequently studied at different pH. These results showed that the drugs have been released in controlled manner. The current investigation proves that the combination of DOX and Kaempferol are more efficient to induce cytotoxic effect while compared to the each drug alone. On the other hand, AO/EtBr and DAPI staining are confirming the induction of apoptosis in cancer cells. In vivo antitumor efficiency of PEGylated AuNPs-DOX@Kaempferol showed a significant reduction in tumor volume without any severe side effects. Thus, combine drug nanoformulations could be a promising drug delivery system for colon cancer therapy.

Preparation and Characterization of Poly(2-oxazoline) Micelles for the Solubilization and Delivery of Water Insoluble Drugs.

Many new drug development candidates are highly lipophilic compounds with low water solubility. This constitutes a formidable challenge for the use of such compounds for cancer therapy, where high doses and intravenous injections are needed ( Di et al., 2012 ). Here, we present a poly(2-oxazoline) polymer (POx)-based nanoformulation strategy to solubilize and deliver hydrophobic drugs. POx micelles are prepared by a simple thin-film hydration method. In this method, the drug and polymer are dissolved in a common solvent and allowed to mix, following which the solvent is evaporated using mild heating conditions to form a thin film. The micelles form spontaneously upon hydration with saline. POx nanoformulation of hydrophobic drugs is unique in that it has a high drug loading capacity, which is superior to micelles of conventional surfactants. Moreover, multiple active pharmaceutical ingredients (APIs) can be included within the same POx micelle, thereby enabling the codelivery of binary as well as ternary drug combinations ( Han et al., 2012 ; He et al., 2016 ).

Intrinsic acetamide brush-off by polyurea biodendrimers.

The presence of genotoxic impurities in active pharmaceutical ingredients (APIs) is a major concern for the pharmaceutical industry. Acetamide is a common genotoxic byproduct found in synthetic routes of many APIs, mainly due to acetonitrile hydrolysis, and selective scavenging is a still a challenging task. Herein, as a proof-of-concept, we evaluate polyurea (PURE) biodendrimers as strategic nanopolymers to prepare safe drug nanoformulations from mixtures containing acetamide, using (S)-ibuprofen (IBF) as a model drug. Furthermore, computational molecular dynamics (MD) simulations were conducted to rationalize in vitro results and to identify the key intermolecular interactions within mixtures. Experimental data were corroborated by MD simulations which showed that acetamide, IBF and carboxyfluorescein interactions with PURE biodendrimers are mostly at the surface. Also, PURE nanoformulations appear to be driven by hydrogen bonding, electrostatic and hydrophobic interactions.

Extracellular Vesicle-Based Therapeutics: Preclinical and Clinical Investigations.

Drug nanoformulations hold remarkable promise for the efficient delivery of therapeutics to a disease site. Unfortunately, artificial nanocarriers, mostly liposomes and polymeric nanoparticles, show limited applications due to the unfavorable pharmacokinetics and rapid clearance from the blood circulation by the reticuloendothelial system (RES). Besides, many of them have high cytotoxicity, low biodegradability, and the inability to cross biological barriers, including the blood brain barrier. Extracellular vesicles (EVs) are novel candidates for drug delivery systems with high bioavailability, exceptional biocompatibility, and low immunogenicity. They provide a means for intercellular communication and the transmission of bioactive compounds to targeted tissues, cells, and organs. These features have made them increasingly attractive as a therapeutic platform in recent years. However, there are many obstacles to designing EV-based therapeutics. In this review, we will outline the main hurdles and limitations for therapeutic and clinical applications of drug loaded EV formulations and describe various attempts to solve these problems.

Anticancer potential of docetaxel-loaded cobalt ferrite nanocarrier: an in vitro study on MCF-7 and MDA-MB-231 cell lines

Aim To develop a biocompatible cobalt ferrite (CF-NP) nanodrug formulation using oleic acid and poly (d,l-lactide-co-glycolic) acid (PLGA) for the delivery of docetaxel (DTX) specifically to breast cancer cells. Methods The CF-NP were synthesised by hydrothermal method and conjugated with DTX in a PLGA matrix and were systematically characterised using XRD, FE-SEM, TEM, DLS, FTIR, TGA, SQUID etc. The drug loading, in vitro drug release, cellular uptake, cytotoxicity were evaluated and haemolytic effect was studied. Results The CF-NP showed good crystallinity with an average particle size of 21 nm and ferromagnetic nature. The DTX-loaded CF-NP (DCF-NP) showed 8.4% (w/w) drug loading with 81.8% loading efficiency with a sustained DTX release over time. An effective internalisation and anti-proliferative efficiency was observed in MCF-7 and MDA-MB-231 breast cancer cells and negligible haemolytic effect. Conclusion The DCF-NP can have the potential for the effective delivery of DTX for breast cancer treatment.