Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy.

As a new form of regulated cell death, ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells. The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells. Due to their high loading and structural tunability, nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting. This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis. Additionally, we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

Hesperidin-loaded cubogel as a novel therapeutic armamentarium for full-thickness wound healing.

Wounds are a physical manifestation of injury to the skin causing it to rupture or tear. The process of wound healing naturally restores skin integrity while minimizing the extent of the damage. Hesperidin (HPN) is a natural polyphenolic flavonoid and is effective in treating wounds due to its ability to reduce inflammation and stimulate angiogenesis. However, its use is limited by its poor physicochemical attributes such as poor solubility in water. Recently, nanoparticles, particularly Cubosomes, are found to be promising candidates for advancing wound-healing therapies, owing to their unique properties. The present study was conducted to develop a hydrogel system based on Cubosomes encapsulating HPN (HPN-Cubogel), with the potential to mitigate full-thickness wounds. The therapeutic efficacy of the formulation assessed in the animal model showed that the HPN-Cubogel formulation group exhibited a wound closure rate of 98.96 ± 1.50% after 14 days post-wounding compared to 89.12 ± 2.6% in the control group suggesting superior wound contraction activity. Collagen synthesis was superior in the formulation compared to the control group, as determined through MT staining. In summary, the HPN-Cubogel formulation was found to be the most effective in enhancing full-thickness wound healing.

Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches.

Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, treatments available till date including phytocompounds, chemotherapy, radiotherapy, photothermal therapy, surgery, combination therapy, molecular targets associated with cancer growth and metastasis, and special emphasis on nanotechnology-based approaches for downregulating the deleterious disease. A detailed analysis with respect to types of nanoparticles and their scope in overcoming multidrug resistance as well as associated clinical trials has been discussed.

Lipid polymer hybrid nanoparticles: a custom-tailored next-generation approach for cancer therapeutics.

Lipid-based polymeric nanoparticles are the highly popular carrier systems for cancer drug therapy. But presently, detailed investigations have revealed their flaws as drug delivery carriers. Lipid polymer hybrid nanoparticles (LPHNPs) are advanced core-shell nanoconstructs with a polymeric core region enclosed by a lipidic layer, presumed to be derived from both liposomes and polymeric nanounits. This unique concept is of utmost importance as a combinable drug delivery platform in oncology due to its dual structured character. To add advantage and restrict one's limitation by other, LPHNPs have been designed so to gain number of advantages such as stability, high loading of cargo, increased biocompatibility, rate-limiting controlled release, and elevated drug half-lives as well as therapeutic effectiveness while minimizing their drawbacks. The outer shell, in particular, can be functionalized in a variety of ways with stimuli-responsive moieties and ligands to provide intelligent holding and for active targeting of antineoplastic medicines, transport of genes, and theragnostic. This review comprehensively provides insight into recent substantial advancements in developing strategies for treating various cancer using LPHNPs. The bioactivity assessment factors have also been highlighted with a discussion of LPHNPs future clinical prospects.

Hyaluronic acid engineered gallic acid embedded chitosan nanoparticle as an effective delivery system for treatment of psoriasis.

Psoriasis is a deleterious auto-immune disorder which seriously harms the patients physical and mental health. CD44 are found to be over-expressed on psoriatic lesions which are highly responsible for epidermal hyperproliferation and inflammation. Gallic acid (GA), a phenolic acid natural compound has potential inhibitory impact on pro-inflammatory transcription factors. However, the penetration across skin and availability is low when applied topically, making the treatment extremely challenging. Considering such factors, we developed GA loaded chitosan nanoparticles and modified with hyaluronic acid (HA) (HA@CS-GA NP) to assess the therapeutic potential against psoriasis. The formulations were characterized by DSC, zetasizer and TEM for assuring the development of nanosystems. GA loaded CS NP had a particle size of 207.2 ± 0.08 nm while after coating with HA, the size increased to 220.1 ± 0.18 nm. The entrapment efficiency was 93.24 ± 0.132% and drug loading of 73.17 ± 0.23%. The in vitro cell viability assessment study confirmed enhanced anti-proliferative effect of HA@CS-GA NP over plain GA which is due to high sensitivity towards HaCaT cell. The in vivo results on imiquimod induced psoriasis model indicated that CD44 receptor mediated targeted approach of HA@CS-GA NP gel had great potential in restricting the keratinocyte hyperproliferation and circumventing psoriasis. For the therapy of further skin-related conditions, HA modified nanoparticles should be investigated extensively employing genes, antibodies, chemotherapeutics, or natural substances.

Drug permeation enhancement, efficacy, and safety assessment of azelaic acid loaded SNEDDS hydrogel to overcome the treatment barriers of atopic dermatitis.

Atopic dermatitis is one of the most widespread chronic inflammatory skin conditions that can occur at any age, though the prevalence is highest in children. The purpose of the current study was to prepare and optimize the azelaic acid (AzA) loaded SNEDDS using Pseudo ternary phase diagram, which was subsequently incorporated into the Carbopol 940 hydrogel for the treatment of atopic dermatitis. The composition was evaluated for size, entrapment efficiency, in vitro, ex vivo, and in vivo studies. The polydispersity index of the optimized preparation was found to be less than 0.5, and the size of the distributed globules was found to be 151.20 ± 3.67 nm. The SNEDDS hydrogel was characterized for pH, viscosity, spreadability, and texture analysis. When compared to the marketed formulation, SNEDDS hydrogel was found to have a higher rate of permeation through the rat skin. In addition, a skin irritation test carried out on experimental animals showed that the SNEDDS formulation did not exhibit any erythematous symptoms after a 24-h exposure. In conclusion, the topical delivery of AzA through the skin using SNEDDS hydrogel could prove to be an effective approach for the treatment of atopic dermatitis.

Self-assembled Gallic acid loaded lecithin-chitosan hybrid nanostructured gel as a potential tool against imiquimod-induced psoriasis.

Increased thickness of the skin and hyperproliferation of keratinocyte cell is the main obstacle in the treatment of psoriasis. Gallic Acid (GA) has shown efficacious results against the hyperproliferation of keratinocytes while lipid-polymer loaded hybrid nanoparticles (LPHNs) have an edge over lipidic and polymeric nanoparticles considering drug loading, controlled release, stability, and retention. The LPHNs were optimized using Box-Behnken method and was further characterized by FTIR, DSC and Zetasizer. The optimized preparation demonstrated a size of 170.5 ± 0.087 nm and a PDI of 0.19 ± 0.0015, respectively. The confocal study has suggested that the hybrid nanosystem enhanced the drug penetration into the deeper layer with a higher drug release of 79 ± 0.001% as compared to the gallic acid-loaded gel. In addition, the formulation significantly reduced PASI score and splenomegaly without causing any serious irritation. The morphological study of the spleen suggested that the prepared formulation has well controlled the disease compared to the marketed formulation while maintaining a normal level of immune cells after treatment. Hence GALPHN could be accepted as one of the excellent vehicles for the topical conveyance of GA (gallic acid) due to enhanced penetration, and good retention, along with fewer side effects and higher efficacy of the GALPHN gel against imiquimod (IMQ) induced psoriasis.

Advanced multifunctional nano-lipid carrier loaded gel for targeted delivery of 5-flurouracil and cannabidiol against non-melanoma skin cancer.

Non-melanoma skin cancer is one of the most common malignancies reported around the globe. Current treatment therapies fail to meet the desired therapeutic efficacy due to high degree of drug resistance. Thus, there is prominent demand in advancing the current conventional therapy to achieve desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The current investigation has been designed to evaluate the safety and efficacy of developed 5-Flurouracil and cannabidiol loaded combinatorial lipid-based nanocarrier (FU-CBD NLCs) gel for the effective treatment of skin cancer. Initially, confocal microscopy study results showed excellent uptake and deposition at epidermal and the dermal layer. Irritation studies performed by IR camera and HET cam shows FU-CBD NLCs was much more tolerated and less irritant compared to conventional treatment. Furthermore, gamma scintigraphy evaluation shows the skin retention behavior of the formulation. Later, in-ovo tumor remission studies were performed, and it was found that prepared FU-CBD NLCs was able to reduce tumor volume significantly compared to conventional formulation. Thus, obtained results disclosed that permeation and disposition of 5-FU and CBD into different layers of the skin FU-CBD NLCs gel could be more potential carrier than conventional gel. Furthermore, prepared formulation showed greater tumor remission, better survival rate, reduction in tumor number, area, and volume with improved biochemical profile. Thus, prepared gel could serve as a promising formulation approach for the skin cancer treatment.

Gold nanoparticles and gold nanorods in the landscape of cancer therapy.

Cancer is a grievous disease whose treatment requires a more efficient, non-invasive therapy, associated with minimal side effects. Gold nanoparticles possessing greatly impressive optical properties have been a forerunner in bioengineered cancer therapy. This theranostic system has gained immense popularity and finds its application in the field of molecular detection, biological imaging, cancer cell targeting, etc. The photothermal property of nanoparticles, especially of gold nanorods, causes absorption of the light incident by the light source, and transforms it into heat, resulting in tumor cell destruction. This review describes the different optical features of gold nanoparticles and summarizes the advance research done for the application of gold nanoparticles and precisely gold nanorods for combating various cancers including breast, lung, colon, oral, prostate, and pancreatic cancer.

Recent advancement on albumin nanoparticles in treating lung carcinoma.

With the advancement of nanotechnology, many different forms of nanoparticles (NPs) are created, which specifically enhance anticancer drug delivery to tumour cells. Albumin bio-macromolecule is a flexible protein carrier for the delivery of drugs that is biodegradable, biocompatible, and non-toxic. As a result, it presents itself as an ideal material for developing nanoparticles for anticancer drug delivery. Toxicological investigations demonstrated that this novel drug delivery technique is safe for use in the human population. Furthermore, drug compatibility with the albumin nanoparticle is remarkable. The robust structure of the nanoparticle, high drug encapsulation, and customisable drug release make it a promising carrier option for the treatment of lung cancer. In this review, we summarise human serum albumin and bovine serum albumin in the targeted delivery of anticancer drugs to lung cancer cells.

A review of various analytical methods for the estimation of olanzapine: An antipsychotic drug.

Olanzapine (OLZ) is an antipsychotic agent and is a thienobenzodiazepine derivative. It is used either in combination with other drugs like carbamazepine, simvastatin, and clozapine or as a single drug. The present work is mainly focused on various approaches for OLZ analysis in bulk drugs as well as on their pharmaceutical formulations. It is also focused on various bioanalytical methods used for analysis. Our survey showed that many analytical techniques were carried out using UV spectrophotometry, MS, LC-MS/MS techniques, and chromatographic techniques like HPLC and high-performance thin layer chromatography in both bulk and solid dosage forms. Bioanalytical techniques were also performed using human plasma or serum. The analysis was carried out either for a single drug or for a combination of drugs. This review shows the rate of use of the different methodologies for OLZ analysis. A considerable amount of information was collected and utilized for the strategies.

Rescue effect of curcumin against copper toxicity.

Turmeric has long been used not only as an indispensable part of Asian cuisine but as a medicinal herb for dressing wounds, bites, burns, treating eye infections and acne. Curcuminoids are the active substances and their synthetic derivatives (i.e. diacetylcurcumin (DAC) and metal-curcumin complexes) possess an incredibly wide range of medicinal properties that encompass chelation capacity for multiple heavy metals, antioxidant activity, anti-inflammatory properties, cytotoxicity against cancerous cells, antiviral and antibacterial effects, antihypertensive and insulin sensitizing role, and regulatory role on apoptosis. The aforementioned properties have put curcumin on spotlight as a potential treatment for ailments such as, hepatic diseases, neurodegenerative diseases, metabolic syndrome, dyslipidemia, cardiovascular disease, auto-immune diseases, malignancies and conditions associated with metal overload. Copper is essential for major biological functions, however, an excess causes chronic ailments including neurodegenerative disorders. The fascinating approach of curcumin could alleviate such effect by forming a complex. Thus, this review aims to present available data on the effect of copper-curcumin interaction in various in vitro, ex-vivo in vivo, and clinical studies.

GLUT1 transporter-facilitated solid lipid nanoparticles loaded with anti-cancer therapeutics for ovarian cancer targeting.

The therapeutics available for cancer treatment have the major hurdle of site-specific delivery of anti-cancer drugs to the tumor site and non-target specific side effects. The standard therapy for ovarian cancer still poses numerous pitfalls due to the irrational use of drugs affecting healthy cells. As an appealing approach, nanomedicine could revamp the therapeutic profile of anti-cancer agents. Owing to the low manufacturing cost, increased biocompatibility, and modifiable surface properties, lipid-based nanocarriers, particularly solid lipid nanoparticles (SLN), have remarkable drug delivery properties in cancer treatment. Given the extra-ordinary benefits, we developed anti-neoplastic (paclitaxel) drug-loaded SLN (PTX-SLN) and functionalized with N-acetyl-d-glucosamine (GLcNAc) (GLcNAc-PTX-SLN) to reduce the rate of proliferation, growth, and metastasis of ovarian cancer cells over-expressing GLUT1 transporters. The particles presented considerable size and distribution while demonstrating haemocompatibility. Using GLcNAc modified form of SLNs, confocal microscopy, MTT assay, and flow cytometry study demonstrated higher cellular uptake and significant cytotoxic effect. Also, molecular docking results established excellent binding affinity between GLcNAc and GLUT1, complimenting the feasibility of the therapeutic approach in targeted cancer therapy. Following the compendium of target-specific drug delivery by SLN, our results demonstrated a significant response for ovarian cancer therapy.

Unravelling the enigma of siRNA and aptamer mediated therapies against pancreatic cancer.

Pancreatic cancer (PC) is a fatal disease that has a poor 5-year survival rate. The poor prognosis can be attributed to both troublesome detections at the initial stage, which makes the majority of the treatment options largely unsuccessful and leads to extensive metastasis, as well as to its distinct pathophysiological characteristics, such as rich desmoplastic tumours bounded by dysplastic and hypo perfused vessels restricting the mobility of therapeutic agents. Continued attempts have been made to utilise innovative measures for battling PC to increase the therapeutic effectiveness of therapies and overcome their cytotoxicity. Combined cancer targeting and gene silencing approach has shown improved outcomes in patients' survival rates and quality of life, offering a potential solution to therapeutic complications. It particularly targets various barriers to alleviate delivery problems and diminish tumour recurrence and metastasis. While aptamers, a type of single-stranded nucleic acids with strong binding affinity and specificity to target molecules, have recently surfaced as a viable PC strategy, siRNA can interfere with the expression of certain genes. By concurrently suppressing genes and boosting targeted approach, the cocktail of siRNA/Aptamer and other therapeutic drugs can circumvent the multi-drug resistance phenomena. Additionally, combination therapy with additive or synergistic effects can considerably increase the therapeutic efficacy of anti-cancer medications. This study outlines the primary difficulties in treating PC, along with recent developments in siRNA/Aptamer mediated drug delivery to solve the major hiccup of oncology field.

Formulation and development of novel lipid-based combinatorial advanced nanoformulation for effective treatment of non-melanoma skin cancer.

Non-melanoma skin cancer is one of the most common malignancies reported with high number of morbidities, demanding an advanced treatment option with superior chemotherapeutic effects. Due to high degree of drug resistance, conventional therapy fails to meet the desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The NLCs were optimized using central composite design that showed an average particle size of 206 nm and a zeta potential of -34 mV. In addition, in vitro and ex vivo drug permeations studies demonstrated the effective delivery of both drugs in the skin layers via lipid structured nanocarriers. Also, the prepared FU-CBD-NLCs showed promising effect in-vitro cell studies including MTT assays, wound healing and cell cycle as compared to the conventional formulation. Moreover, dermatokinetic studies shows there was superior deposition of drugs at epidermal and the dermal layer when treated with FU-CBD-NLCs. In the end, overall study offered a novel combinatorial chemotherapy that could be an option for the treatment of non-melanoma skin cancer.

Folic acid engineered sulforaphane loaded microbeads for targeting breast cancer.

Non-targeted cancer therapy poses a huge risk to the cancer patients' life due to high toxicity offered by chemotherapy. Breast carcinoma is one of such deleterious disease, demanding a highly effectual treatment option which could reduce the toxicity and extend survival rate. Since, folate receptors extensively display themselves on the cancer cell surface, targeting them would help to ameliorate the progression and metastasis. Considering this, we envisaged and developed sulforaphane loaded folate engineered microbeads to target breast cancer cells over-expressing folate receptors. The surface engineered microbeads were optimized and developed using emulsion gelation technique, among which the best developed preparation demonstrated the particle size of 1302 ± 3.98 µm, % EE of 84.1 ± 3.32% and in vitro drug release of 98.1 ± 4.42%@24h. The spherical sized microbead showed controlled release with improved haem-compatibility in comparison to the bare drug. Free radical scavenging activity by ABTS assay showed strong anti-oxidant activity (IC50 20.62 µg/ml) of the targeted microbeads with profound cancer cell sup pressing effect (IC50 17.48 ± 3.5 µM) as observed in MCF-7 cells by MTT assay. Finally, in comparison to lone SFN, the targeted therapy showed enhanced uptake by the intestinal villi indicating a suitable oral targeted therapy against breast carcinoma.

Lipid-based nanocarrier mediated CRISPR/Cas9 delivery for cancer therapy.

CRISPR/Cas mediated gene-editing has opened new avenues for therapies that show great potential for treating or curing cancers, genetic disorders, and microbial infections such as HIV. CRISPR/Cas9 tool is highly efficacious in revolutionizing the advent of genome editing; however, its efficient and safe delivery is a major hurdle due to its cellular impermeability and instability. Nano vectors could be explored to scale up the safe and effective delivery of CRISPR/Cas9. This review highlights the importance of CRISPR/Cas9 genome editing system in cancer treatment along with the effect of lipid-based nanoparticles in its safe delivery to cancer cells. The solid-lipid nanoparticles, nanostructured lipid carrier, lipid nanoparticles and niosomes have shown great effect in the delivery of CRISPR compounds to the cancer cells. The design and genome editing application in cancer therapy has been discussed along with the future concern and prospects of lipid nanoparticle based CRISPR/Cas9 has been focused toward the end.

The clinical significance of 4D printing.

4D printing is the next step on from 3D printing involving the fourth dimension of 'time'. The programmed 4D-printed objects are capable of changing their shape in response to external stimuli, such as light, heat, or water, differentiating them from 3D-printed static objects. This technique promises new possibilities for cancer treatment, drug delivery, stent development, and tissue engineering. In this review, we focus on the development of 4D-printed objects, their clinical use, and the possibility of 5D printing, which could revolutionize the fields of biomedical engineering and drug delivery.

Itraconazole and Difluorinated-Curcumin Containing Chitosan Nanoparticle Loaded Hydrogel for Amelioration of Onychomycosis.

Onychomycosis is a nail infection caused by a fungus, Trichophyton mentagrophytes, that is responsible for major nail infections. The best method suited for treating such infections generally includes a topical remedy. However, conventional oral or topical formulations are associated with various limitations. Therefore, a more efficient and compatible formulation is developed in this study. The primary objective of the current study is to formulate and evaluate chitosan nanoparticle-based hydrogel for ameliorating onychomycosis. The sole purpose of this research was to increase the permeation of the lipophilic drug itraconazole and difluorinated curcumin, and its synergistic antifungal activity was also evaluated for the first time. Both in vitro and ex vivo drug release evaluations confirmed the sustained release of both drugs from the hydrogel, which is a prerequisite for treating onychomycosis. The results overall highlighted the promising activity of a synergistic approach that could be implemented for the treatment of onychomycosis. The hydrogel-based formulation serves as an effective method of delivery of drugs across the layers of the skin, resulting from its hydrating characteristics.

Precision medicine: Ray of hope in overcoming cancer multidrug resistance.

Multi-drug resistance (MDR) developed in response to chemotherapy is one of the prominent causes of therapeutic failure. The major underlying factors that contribute to such malignancies include tumor microenvironment, genetic alterations, changes at the cellular level and most of all the heterogeneity of tumors. Recent advances in the field of oncology have prompted a mechanistic understanding of the human genome which is responsible for such alterations, upon which the therapy would be designed. Such an approach that administers drugs by targeting the molecular changes is attributed to precision medicine. Precision medicine helps design therapy as per the requirement of patients based on the sharing of similar complex tumor environments. This revolutionized approach would help in early detection, better targeting, improved patient compliance and survival along with much reduced toxicity otherwise evidenced in conventional cancer therapy. This review discusses the cause of MDR, highlighting the role of precision medicine in overcoming such critical events. Major limitations and future prospects are also highlighted.