Overcoming biological barriers with block copolymers-based self-assembled nanocarriers. Recent advances in delivery of anticancer therapeutics

Cancer is one of the most common life-threatening illness and it is the world’s second largest cause of death. Chemotherapeutic anticancer drugs have many disadvantages, which led to the need to develop novel strategies to overcome these shortcomings. Moreover, tumors are heterogenous in nature and there are various biological barriers that assist in treatment reisistance. In this sense, nanotechnology has provided new strategies for delivery of anticancer therapeutics. Recently, delivery platforms for overcoming biological barriers raised by tumor cells and tumor-bearing hosts have been reported. Among them, amphiphilic block copolymers (ABC)-based self-assembled nanocarriers have attracted researchers worldwide owing to their unique properties. In this work, we addressed different biological barriers for effective cancer treatment along with several strategies to overcome them by using ABC‐based self-assembled nanostructures, with special emphasis in those that have the ability to act as responsive nanocarriers to internal or external environmental clues to trigger release of the payload. These nanocarriers have shown promising properties to revolutionize cancer treatment and diagnosis, but there are still challenges for their successful translation to clinical applications.Fil: Torres, Jazmin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Dhas, Namdev. Nirma University. Institute Of Pharmacy; IndiaFil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentin

Co-rotating twin screw process for continuous manufacturing of solid crystal suspension: A promising strategy to enhance the solubility, permeation and oral bioavailability of Carvedilol [version 3; peer review: 1 approved, 2 approved with reservations]

Background In the current work, co-rotating twin-screw processor (TSP) was utilized to formulate solid crystal suspension (SCS) of carvedilol (CAR) for enhancing its solubility, dissolution rate, permeation and bioavailability using mannitol as a hydrophilic carrier. Methods In-silico molecular dynamics (MD) studies were done to simulate the interaction of CAR with mannitol at different kneading zone temperatures (KZT). Based on these studies, the optimal CAR: mannitol ratios and the kneading zone temperatures for CAR solubility enhancement were assessed. The CAR-SCS was optimized utilizing Design-of-Experiments (DoE) methodology using the Box-Behnken design. Saturation solubility studies and in vitro dissolution studies were performed for all the formulations. Physicochemical characterization was performed using differential scanning calorimetry , Fourier transform infrared spectroscopy, X-ray diffraction studies, and Raman spectroscopy analysis. Ex vivo permeation studies and in vivo pharmacokinetic studies for the CAR-SCS were performed. Stability studies were performed for the DoE-optimized CAR-SCS at accelerated stability conditions at 40 ºC/ 75% RH for three months. Results Experimentally, the formulation with CAR: mannitol ratio of 20:80, prepared using a KZT of 120 ºC at 100 rpm screw speed showed the highest solubility enhancement accounting for 50-fold compared to the plain CAR. Physicochemical characterization confirmed the crystalline state of DoE-optimized CAR-SCS. In-vitro dissolution studies indicated a 6.03-fold and 3.40-fold enhancement in the dissolution rate of optimized CAR-SCS in pH 1.2 HCl solution and phosphate buffer pH 6.8, respectively, as compared to the pure CAR. The enhanced efficacy of the optimized CAR-SCS was indicated in the ex vivo and in vivo pharmacokinetic studies wherein the apparent permeability was enhanced 1.84-fold and bioavailability enhanced 1.50-folds compared to the plain CAR. The stability studies showed good stability concerning the drug content. Conclusions TSP technology could be utilized to enhance the solubility, bioavailability and permeation of poor soluble CAR by preparing the SCS

2D Hetero-Nanoconstructs of Black Phosphorus for Breast Cancer Theragnosis: Technological Advancements

As per global cancer statistics of 2020, female breast cancer is the most commonly diagnosed cancer and also the foremost cause of cancer death in women. Traditional treatments include a number of negative effects, making it necessary to investigate novel smart drug delivery methods and identify new therapeutic approaches. Efforts for developing novel strategies for breast cancer therapy are being devised worldwide by various research groups. Currently, two-dimensional black phosphorus nanosheets (BPNSs) have attracted considerable attention and are best suited for theranostic nanomedicine. Particularly, their characteristics, including drug loading efficacy, biocompatibility, optical, thermal, electrical, and phototherapeutic characteristics, support their growing demand as a potential substitute for graphene-based nanomaterials in biomedical applications. In this review, we have explained different platforms of BP nanomaterials for breast cancer management, their structures, functionalization approaches, and general methods of synthesis. Various characteristics of BP nanomaterials that make them suitable for cancer therapy and diagnosis, such as large surface area, nontoxicity, solubility, biodegradability, and excellent near-infrared (NIR) absorption capability, are discussed in the later sections. Next, we summarize targeting approaches using various strategies for effective therapy with BP nanoplatforms. Then, we describe applications of BP nanomaterials for breast cancer treatment, which include drug delivery, codelivery of drugs, photodynamic therapy, photothermal therapy, combined therapy, gene therapy, immunotherapy, and multidrug resistance reversal strategy. Finally, the present challenges and future aspects of BP nanomaterials are discussed

Fostering the unleashing potential of nanocarriers-mediated delivery of ocular therapeutics

Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the physiological static barriers such as the complex layers of the cornea, sclera and retina which restrict the drug from permeating into the anterior and posterior segments of the eye. Recent years have witnessed inventions in the field of conventional and nanocarrier drug delivery which have shown considerable enhancement in delivering small to large molecules across the eye. The dynamic challenges associated with conventional systems include limited drug contact time and inadequate ocular bioavailability resulting from solution drainage, tear turnover, and dilution or lacrimation. To this end, various bioactive-based nanosized carriers including liposomes, ethosomes, niosomes, dendrimer, nanogel, nanofibers, contact lenses, nanoprobes, selenium nanobells, nanosponge, polymeric micelles, silver nanoparticles, and gold nanoparticles among others have been developed to circumvent the limitations associated with the conventional dosage forms. These nanocarriers have been shown to achieve enhanced drug permeation or retention and prolong drug release in the ocular tissue due to their better tissue adherence. The surface charge and the size of nanocarriers (10–1000 nm) are the important key factors to overcome ocular barriers. Various nanocarriers have been shown to deliver active therapeutic molecules including timolol maleate, ampicillin, natamycin, voriconazole, cyclosporine A, dexamethasone, moxifloxacin, and fluconazole among others for the treatment of anterior and posterior eye diseases. Taken together, in a nutshell, this extensive review provides a comprehensive perspective on the numerous facets of ocular drug delivery with a special focus on bioactive nanocarrier-based approaches, including the difficulties and constraints involved in the fabrication of nanocarriers. This also provides the detailed invention, applications, biodistribution and safety-toxicity of nanocarriers-based therapeutcis for the ophthalmic delivery.</p

Nanoparticle drug delivery systems in hepatocellular carcinoma: A focus on targeting strategies and therapeutic applications

Hepatocellular carcinoma (HCC) is recognized as a global health issue accounting for millions of deaths every year. Surgery, liver ablation, and embolization therapy are amongst the conventional methods for treatment of HCC. Chemotherapy plays a major role in HCC therapy, however, owing to its conventional pharmacotherapy limitations, it necessitates the development of novel therapeutic strategies. In contrast, nanomedicines for HCC have shown remarkable prospects for solving these complications in HCC owing to their high stability, controlled release, and high drug loading capacity. This review gives an insight into the nano-constructs used for HCC treatment and its active and passive targeting strategies. This review also inculcates the various approaches for targeting the liver cells, its targeting moieties and the conjugation chemistries involved in surface functionalization. A brief description of various therapeutic approaches in the treatment of HCC has also been discussed

Sulfobutylether-β-cyclodextrin: A functional biopolymer for drug delivery applications

Sulfobutylether β-cyclodextrin (SBE-β-CD) is a polyanionic cyclic oligosaccharide that contains glucopyranose units forming a torus ring-like structure. SBE-β-CD is gifted with many favorable properties viz. relatively high solubility (>50 folds compared to β-CD), improved stability, and biocompatibility that praised SBE-β-CD as a smart polymer for drug delivery applications. Commercially, SBE-β-CD is popular by its brand name Captisol®. The present review discusses the structure, properties, and preparation methods of SBE-β-CD-based inclusion complexes (ICs). Furthermore, we discuss here the preparation and applications of SBE-β-CD ICs-based nanoparticulate drug delivery systems, which combines the merits of both, ICs (enhanced solubility) and nanoparticles (NPs, targeted therapy). Patents on and FDA-approved Captisol®-enabled products are tabulated in the benefit of readers. The toxicological aspects and current clinical status of SBE-β-CD or SBE-β-CD-based products are briefly explained in the present review. In our opinion, the present review would be a pathfinder to allow dissemination of information on SBE-β-CD.Fil: Pardeshi, Chandrakantsing V.. No especifíca;Fil: Kothawade, Rucha V.. No especifíca;Fil: Markad, Ashwini R.. No especifíca;Fil: Pardeshi, Sagar R.. St. John Institute of Pharmacy and Research; IndiaFil: Kulkarni, Abhijeet D.. Sandip University; IndiaFil: Chaudhari, Prashant J.. No especifíca;Fil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Dhas, Namdev. No especifíca;Fil: Naik, Jitendra B.. Kavayitri Bahinabai Chaudhari North Maharashtra University; IndiaFil: Surana, Sanjay J.. No especifíca;Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentin

Surface architectured black phosphorous nanoconstructs based smart and versatile platform for cancer theranostics

Black Phosphorous has recently gained the attention in the field of 2D nanomaterials owing to its exceptional structure and properties. Specifically, its features like drug loading efficiency, biocompatibility, optical, mechanical, electrical, thermal and phototherapeutic properties contribute to its rising demand as potential alternative to the graphene-based 2D nanomaterials in biomedical applications. Though the BP's outlook appears promising, its practical applicability is highly challenging. In this review we have discussed the different strategies for synthesis of BP and then briefed its unique properties which renders it a potential platform for the biomedical application. We then discuss the importance of heterogeneous doping on improving the stability of BP against chemical degradation and enhancing its photoelectric properties. Meanwhile, BP-based nanoconjugates, stimuli responsive nanoplatforms, therapeutic, imaging and biosensing platforms are the domains of special and comprehensive interest for versatile biomedical applications of BP. The physicochemical interactions at the nano-bio interface like protein corona formation on the surface on nanoparticles due to interaction with the plasma proteins and others play a crucial role in the biological effects of BP. Hence, we have also discussed the recent studies on interactions between Black phosphorus based nanoconstructs with various biological molecules. Further, it is vital to consider the fact that, though biocompatible, BP-nanomaterials can induce inflammatory responses and exhibit toxicity in dose and time dependant manner. Therefore, we have briefed the biodegradation and toxicological aspects of BP to enlighten the readers about the safety and toxicity of black phosphorous. The future developments of this 2D nanomaterial will not only serve as a boon for oncology, but also functions as a potential nanoplatform for other biomedical applications.Fil: Pandey, Abhijeet. Manipal College Of Pharmaceutical Sciences; IndiaFil: Nikam, Ajinkya Nitin. Manipal College Of Pharmaceutical Sciences; IndiaFil: Padya, Bharath Singh. Manipal College Of Pharmaceutical Sciences; IndiaFil: Kulkarni, Sanjay. Manipal College Of Pharmaceutical Sciences; IndiaFil: Fernandes, Gasper. Manipal College Of Pharmaceutical Sciences; IndiaFil: Shreya, Ajjappla Basavaraj. Manipal College Of Pharmaceutical Sciences; IndiaFil: García, Mónica Cristina. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Caro, Carlos. Universidad de Málaga; EspañaFil: Páez Muñoz, Jose Maria. Universidad de Málaga; EspañaFil: Dhas, Namdev. Sres Sanjivani College Of Parmaceutical Education And Research; India. Nirma University. Institute Of Pharmacy; IndiaFil: García Martín, Maria Luisa. Universidad de Málaga; EspañaFil: Mehta, Tejal. Nirma University. Institute Of Pharmacy; IndiaFil: Mutalik, Srinivas. Manipal College Of Pharmaceutical Sciences; Indi

Recent advancements in nanomaterial-mediated ferroptosis-induced cancer therapy: Importance of molecular dynamics and novel strategies

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs from other forms of cell death, such as apoptosis and necrosis. Molecular therapeutics have hard time playing the long-acting role of ferroptosis induction due to their limited water solubility, low cell targeting capacity, and quick metabolism in vivo. To this end, small molecule inducers based on biological factors have long been used as strategy to induce cell death. Research into ferroptosis and advancements in nanotechnology have led to the discovery that nanomaterials are superior to biological medications in triggering ferroptosis. Nanomaterials derived from iron can enhance ferroptosis induction by directly releasing large quantities of iron and increasing cell ROS levels. Moreover, utilizing nanomaterials to promote programmed cell death minimizes the probability of unfavorable effects induced by mutations in cancer-associated genes such as RAS and TP53. Taken together, this review summarizes the molecular mechanisms involved in ferroptosis along with the classification of ferroptosis induction. It also emphasized the importance of cell organelles in the control of ferroptosis in cancer therapy. The nanomaterials that trigger ferroptosis are categorized and explained. Iron-based and noniron-based nanomaterials with their characterization at the molecular and cellular levels have been explored, which will be useful for inducing ferroptosis that leads to reduced tumor growth. Within this framework, we offer a synopsis, which traverses the well-established mechanism of ferroptosis and offers practical suggestions for the design and therapeutic use of nanomaterials.</p