Chitosan nanocarriers for microRNA delivery and detection: A preliminary review with emphasis on cancer.

In recent years, gene therapy based on miRNA has been employed as a potential growing technique for treating various co-morbidities. Direct administration of miRNA is unrealistic due to their lower specificity, stability, and decreased penetration through the cellular membrane. Suitable delivery vectors must be required to deliver miRNA efficiently. Non-viral vectors can be composed of polymeric, lipids, or inorganic components/nanocarriers. Among different cationic polymers, chitosan nanocarriers are effectively utilized to deliver miRNA owing to its cationic nature, biodegradability, biocompatibility, and increased potential for functional modifications. Therefore, chitosan has been widely employed to effectively deliver several miRNAs to the target site. This review will discuss the recent signs of progress and future perspectives in delivering and detecting miRNAs via chitosan and its derivatives with an emphasis on cancer. The review will also provide an insight into the various challenges of these chitosan carriers to be used as delivery agents for miRNA.

Development of an intelligent, stimuli-responsive transdermal system for efficient delivery of Ibuprofen against rheumatoid arthritis.

The present study aimed to fabricate and evaluate the therapeutic efficacy of pH-responsive Ibuprofen (IB) nanoparticles (NPs) loaded transdermal hydrogel against rheumatoid arthritis (RA). The IB loaded Eudragit® L 100 (EL 100) nanoparticles were formulated through a modified nanoprecipitation technique and optimized using central composite design software. The optimized NPs were loaded into Carbopol® 934-based hydrogel by solvent evaporation method and were analyzed for physicochemical characteristics. The mean particle size of the prepared NPs was 48 nm with an entrapment efficiency of 90%. The transdermal hydrogel showed a pH-responsive sustained drug release and high penetration through the skin. Moreover, the prepared nanocarrier system exhibited therapeutic efficacy at inflamed joints' sites both in acute and chronic RA mice model. The therapeutic efficacy of the prepared formulation was confirmed through the results of various behavioral, biochemical, and cytokines-based assays. Similarly, the assessment of histopathological and radiological images, as well as the skin irritation studies further strengthens the potential use of the prepared formulation through the transdermal route. The current findings suggested that IB loaded pH-responsive NPs based transdermal hydrogel can be used as an efficient agent to manage RA.

Nanotechnology-based immunotherapies to combat cancer metastasis.

Emerging concepts in nanotechnology have gained particular attention for their clinical translation of immunotherapies of cancer, autoimmune and infectious diseases. Several nanoconstructs have been engineered with unique structural, physicochemical, and functional features as robust alternatives for conventional chemotherapies. Traditional cancer therapies like chemotherapy, radiotherapy, and ultimately surgery are the most widely practiced in biomedical settings. Biomaterials and nanotechnology have introduced vehicles for drug delivery and have revolutionized the concept of the modern immunotherapeutic paradigm. Various types of nanomaterials, such as nanoparticles and, more specifically, drug-loaded nanoparticles are becoming famous for drug delivery applications because of safety, patient compliance, and smart action. Such therapeutic modalities have acknowledged regulatory endorsement and are being used in twenty-first-century clinical settings. Considering the emerging concepts and landscaping potentialities, herein, we spotlight and discuss nanoparticle-based immunotherapies as a smart and sophisticated drug delivery approach to combat cancer metastasis. The introductory part of this manuscript discusses a broad overview of cancer immunotherapy to understand better the tumor microenvironment and nanotechnology-oriented immunomodulatory strategies to cope with advanced-stage cancers. Following that, most addressable problems allied with conventional immunotherapies are given in comparison to nanoparticle-based immunotherapies. The later half of this work comprehensively highlights the requisite delivery of various bioactive entities with particular cases and examples. Finally, this review also encompasses a comprehensive concluding overview and future standpoints to strengthen a successful clinical translation of nanoparticle-based immunotherapies as a smart and sophisticated drug delivery approach.

Development of novel biopolymer-based nanoparticles loaded cream for potential treatment of topical fungal infections.

OBJECTIVE: Biodegradable polymers are extensively used due to their efficient safety profiles. The aim of the current study was to fabricate, evaluate, and characterize biodegradable, biocompatible fluconazole (FLZ) loaded chitosan (CHS) chondroitin sulfate (CS) nanoparticles (NPs) for topical delivery. Polymers utilized in the formulation not only served as a carrier system but also aided in fighting with complex etiology of the disease due to their innate antifungal activities. METHODS: NPs were prepared by the complex coacervation method, then were optimized for various parameters and subsequently loaded into a cream. RESULTS: Scanning electron microscopic (SEM) analysis showed spherical morphology of the NPs. Prepared NPs showed an average particle size in the range of 350-450 nm and an encapsulation efficiency (EE) of 86%. The polydispersity index (PDI) was found to be 0.148 that showed a uniform distribution of NPs. Fourier transform infrared (FTIR) spectroscopy confirmed the absence of any electrostatic interaction between ingredients. In vitro drug release analyses exhibited a sustained release of the drug and higher antifungal activity than free FLZ. Ex vivo permeability and drug distribution in different skin layers ensured a site-specific delivery of the FLZ-NPs. As compared with free FLZ and other control groups, the prepared NPs also exhibited significantly higher antifungal activity against Candida albicans (p < .01). CONCLUSION: It was concluded from the results that the FLZ-NPs laden cream could be a potential candidate for topical and site-specific delivery of the drug cargo for the potential treatment of fungal infections.

Nanomaterials for the Diagnosis and Treatment of Urinary Tract Infections.

The diagnosis and treatment of urinary tract infections (UTIs) remain challenging due to the lack of convenient assessment techniques and to the resistance to conventional antimicrobial therapy, showing the need for novel approaches to address such problems. In this regard, nanotechnology has a strong potential for both the diagnosis and therapy of UTIs via controlled delivery of antimicrobials upon stable, effective and sustained drug release. On one side, nanoscience allowed the production of various nanomaterial-based evaluation tools as precise, effective, and rapid procedures for the identification of UTIs. On the other side, nanotechnology brought tremendous breakthroughs for the treatment of UTIs based on the use of metallic nanoparticles (NPs) for instance, owing to the antimicrobial properties of metals, or of surface-tailored nanocarriers, allowing to overcome multidrug-resistance and prevent biofilm formation via targeted drug delivery to desired sites of action and preventing the development of cytotoxic processes in healthy cells. The goal of the current study is therefore to present the newest developments for the diagnosis and treatment of UTIs based on nanotechnology procedures in relation to the currently available techniques.

An efficient approach for development and optimisation of curcumin-loaded solid lipid nanoparticles' patch for transdermal delivery.

This study aimed to develop and optimise a Curcumin-loaded SLNs (C-SLNs) patch through a new approach for transdermal delivery. C-SLNs were optimised through the response surface central composite design using the modified injection method. Optimised C-SLNs were loaded into a polyvinyl alcohol-based patch through the backing membrane method. Compatibility studies (FTIR, XRPD), in vitro release, ex vivo skin permeation, accelerated stability, and evaluation studies of the patch were also performed. Prepared C-SLNs exhibited average particle diameter of 170 ± 2 nm with an encapsulation efficiency of 90 ± 3.5% (w/w) while SEM illustrated spherical shape of particles. In vitro release data ensured a sustained release for up to 72 hours. The enhancement ratio of C-SLNs based patch with permeation enhancer (PE) was high up to 6.5 folds as compared to patch without PE. It is concluded that the modified injection method is simple, economical, and less time consuming for the development of C-SLNs patch for the transdermal route.

Recent trends, challenges and future outlook of transdermal drug delivery systems for rheumatoid arthritis therapy.

At present, several drug molecules have been used for the treatment of rheumatoid arthritis (RA). However, the utilization of these compounds through the oral and parenteral route is limited due to low bioavailability, rapid metabolism, poor absorption, first-pass effect, and serious adverse effects. A transdermal delivery system is an appealing option in this scenario, as it possesses the proficiency to overcome drawbacks associated with the oral and parenteral route. With the innovation of several enhancement strategies, many therapeutic agents have been administered transdermally, proposing an exceptional approach to treat RA. The present article provides an insight into the etiology and pathophysiology of RA. The challenges of the transdermal route and the strategies to improve those problems are described. The current advances in increasing the transdermal efficiency of the therapeutics against RA are discussed. Limitations and advantages regarding the state of the art transdermal delivery system and future outlook are also summarized.

Exploiting proteases for cancer theranostic through molecular imaging and drug delivery.

The measurement of biological processes at a molecular and cellular level serves as a basis for molecular imaging. As compared with traditional imaging approaches, molecular imaging functions to probe molecular anomalies that are the basis of a disease rather than the evaluation of end results of these molecular changes. Proteases play central role in tumor invasion, angiogenesis and metastasis thus can be exploited as a target for imaging probes in early diagnosis and treatment of tumors. Molecular imaging of protease has undergone tremendous breakthroughs in the field of diagnosis. It allows the clinicians not only to see the tumor location but also provides an insight into the expression and activity of different types of markers associated with the tumor microenvironment. These imaging techniques are expected to have a huge impact on early cancer detection and personalized cancer treatment. Effective development of protease imaging probes with the highest in vivo biocompatibility, stability and most appropriate pharmacokinetics for clinical translation will upsurge the success level of early cancer detection and treatment.

Surfactant-Free, Self-Assembled Nanomicelles-Based Transdermal Hydrogel for Safe and Targeted Delivery of Methotrexate against Rheumatoid Arthritis.

Methotrexate (MTX) is the first line agent for therapy against rheumatoid arthritis (RA); however, orally its efficacy is hampered by poor solubility, less permeability, short plasma half-life, and reduced bioavailability. Meanwhile, parenteral formulations are associated with severe adverse effects. In an attempt to improve the efficacy of MTX, we synthesized polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock copolymer by a ring-opening copolymerization reaction and used it as a carrier for the fabrication of MTX-loaded nanomicelles. Surfactant-free, self-assembled nanomicelles were prepared by nanoprecipitation technique and optimized through central composite design. The optimized nanomicelles exhibited a size distribution of 31 nm and an encapsulation efficiency of 91%. In vitro, the nanomicelles exhibited hemocompatibility, sustained release, and significantly high uptake in lipopolysaccharide activated macrophages. To facilitate application on the skin, optimized nanomicelles were loaded into a Carbopol 934-based hydrogel with eucalyptus oil as a penetration enhancer. Eucalyptus oil significantly improved the permeation of nanomicelles through the skin (p < 0.001). When the hydrogel was applied on the RA mice model, nanomicelles exhibited preferentially highest accumulation in the inflamed joints than other organs. As compared with the free MTX, MTX nanomicelles significantly improved the pharmacokinetic (4.34-fold greater half-life, 3.68-fold higher AUC0-t, and 3.15-fold higher mean residence time) and pharmacodynamic profile ascertained through low inflammatory cytokines expression, improved oxidation protection, recovered behavioral responses, and radiological analysis. MTX nanomicelles-based hydrogel also significantly reduced the hepatotoxicity and did not activate the immune system. These results suggest that the MTX-loaded nanomicelles-based transdermal hydrogel can prove to be a promising agent against RA.

Development of novel pH-sensitive nanoparticle-based transdermal patch for management of rheumatoid arthritis.

Aim: To formulate and evaluate a pH-responsive nanoparticle (NP)-based patch for efficient transdermal delivery of flurbiprofen against rheumatoid arthritis. Materials & methods: Nanoprecipitation technique was used for preparation of NPs and central composite design was employed for optimization purposes. Optimized NPs were loaded into the transdermal patch by the solvent evaporation method. Results: Prepared NPs exhibited an average size of 69 nm, while NPs loaded onto the transdermal patch showed sustained release and high permeation through the skin. In in vivo studies, the prepared carrier system elucidated high therapeutic potential in both acute and chronic inflammatory models as evident from the results of behavioral, radiological, histopathological and antioxidant analyses. Conclusion: The flurbiprofen-loaded pH-sensitive NP-based transdermal patch has the potential to manage rheumatoid arthritis effectively.

Marine-Derived Biologically Active Compounds for the Potential Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease with a prevalence rate of up to 1% and is significantly considered a common worldwide public health concern. Commercially, several traditional formulations are available to treat RA to some extent. However, these synthetic compounds exert toxicity and considerable side effects even at lower therapeutic concentrations. Considering the above-mentioned critiques, research is underway around the world in finding and exploiting potential alternatives. For instance, marine-derived biologically active compounds have gained much interest and are thus being extensively utilized to confront the confines of in practice counterparts, which have become ineffective for 21st-century medical settings. The utilization of naturally available bioactive compounds and their derivatives can minimize these synthetic compounds' problems to treat RA. Several marine-derived compounds exhibit anti-inflammatory and antioxidant properties and can be effectively used for therapeutic purposes against RA. The results of several studies ensured that the extraction of biologically active compounds from marine sources could provide a new and safe source for drug development against RA. Finally, current challenges, gaps, and future perspectives have been included in this review.

Ligand decorated chitosan as an advanced nanocarrier for targeted delivery: a critical review.

Nontargeted delivery systems present nonspecific delivery, low transfection efficiency and high toxicity. Ligand-conjugated chitosan (CS) nanocarriers have emerged as an outstanding option for achieving active delivery specifically and preferentially to the target sites by exploiting receptors mediated endocytosis. Mannosylated CS nanocarriers have brought tremendous breakthrough in gene therapy and have proven to be an excellent choice for treatment of infectious and inflammatory diseases. Similarly, folate and antibodies-conjugated CS play a significant role in diagnosis and treatment of various cancers. Current evidences obviously propose ligand-decorated CS as an attractive option for diagnosis and treatment of dreadful conditions. In order to bring huge revolution in the field of targeted delivery, challenges associated with these nanocarriers needs to be addressed.

Development of novel pH-sensitive nanoparticles loaded hydrogel for transdermal drug delivery.

OBJECTIVE: Difference of pH that exists between the skin surface and blood circulation can be exploited for transdermal delivery of drug molecules by loading drug into pH-sensitive polymer. Eudragit S100 (ES100), a pH-sensitive polymer having dissolution profile above pH 7.4, is used in oral, ocular, vaginal and topical delivery of drug molecules. However, pH-sensitive potential of this polymer has not been explored for transdermal delivery. The aim of this research work was to exploit the pH-sensitive potential of ES100 as a nanocarrier for transdermal delivery of model drug, that is, Piroxicam. METHODS: Simple nanoprecipitation technique was employed to prepare the nanoparticles and response surface quadratic model was applied to get an optimized formulation. The prepared nanoparticles were characterized and loaded into Carbopol 934 based hydrogel. In vitro release, ex vivo permeation and accelerated stability studies were carried out on the prepared formulation. RESULTS: Particles with an average size of 25-40 nm were obtained with an encapsulation efficiency of 88%. Release studies revealed that nanoparticles remained stable at acidic pH while sustained release with no initial burst effect was observed at pH 7.4 from the hydrogel. Permeation of these nanocarriers from hydrogel matrix showed significant permeation of Piroxicam through mice skin. CONCLUSION: It can be concluded that ES100 based pH-sensitive nanoparticles have potential to be delivered through transdermal route.