Lipid-based nanoparticle-mediated combination therapy for breast cancer management: a comprehensive review.

Breast cancer due to the unpredictable and complex etiopathology combined with the non-availability of any effective drug treatment has become the major root of concern for oncologists globally. The number of women affected by the said disease state is increasing at an alarming rate attributed to environmental and lifestyle changes indicating at the exploration of a novel treatment strategy that can eradicate this aggressive disease. So far, it is treated by promising nanomedicine monotherapy; however, according to the numerous studies conducted, the inadequacy of these nano monotherapies in terms of elevated toxicity and resistance has been reported. This review, therefore, puts forth a new multimodal strategic approach to lipid-based nanoparticle-mediated combination drug delivery in breast cancer, emphasizing the recent advancements. A basic overview about the combination therapy and its index is firstly given. Then, the various nano-based combinations of chemotherapeutics involving the combination delivery of synthetic and herbal agents are discussed along with their examples. Further, the recent exploration of chemotherapeutics co-delivery with small interfering RNA (siRNA) agents has also been explained herein. Finally, a section providing a brief description of the delivery of chemotherapeutic agents with monoclonal antibodies (mAbs) has been presented. From this review, we aim to provide the researchers with deep insight into the novel and much more effective combinational lipid-based nanoparticle-mediated nanomedicines tailored specifically for breast cancer treatment resulting in synergism, enhanced antitumor efficacy, and low toxic effects, subsequently overcoming the hurdles associated with conventional chemotherapy.

Cell-derived nanovesicles from mesenchymal stem cells as extracellular vesicle-mimetics in wound healing.

Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers. Recently, extracellular vesicles (EVs), naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins, lipids, and nucleic acids, have drawn wide attention due to their ability to promote wound healing and tissue regeneration. However, current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes. To circumvent these challenges, bioinspired cell-derived nanovesicles (CDNs) that mimic EVs were obtained by shearing mesenchymal stem cells (MSCs) through membranes with different pore sizes. Physical characterisations and high-throughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs. Moreover, these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway, resulting in enhancement of cell proliferation, cell migration, secretion of growth factors and extracellular matrix proteins, which all promoted tissue regeneration. Of note, MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEG-fibrin scaffold and animal model, accelerating wound healing in vitro and in vivo. These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.

Extracellular Vesicles and Their Mimetics: A Comparative Study of Their Pharmacological Activities and Immunogenicity Profiles.

Extracellular vesicles (EVs), which are miniaturised carriers loaded with functional proteins, lipids, and nucleic acid material, are naturally secreted by cells and show intrinsic pharmacological effects in several conditions. As such, they have the potential to be used for the treatment of various human diseases. However, the low isolation yield and laborious purification process are obstacles to their translation for clinical use. To overcome this problem, our lab developed cell-derived nanovesicles (CDNs), which are EV mimetics produced by shearing cells through membrane-fitted spin cups. To evaluate the similarities between EVs and CDNs, we compare the physical properties and biochemical composition of monocytic U937 EVs and U937 CDNs. Besides having similar hydrodynamic diameters, the produced CDNs had proteomic, lipidomic, and miRNA profiles with key communalities compared to those of natural EVs. Further characterisation was conducted to examine if CDNs could exhibit similar pharmacological activities and immunogenicity when administered in vivo. Consistently, CDNs and EVs modulated inflammation and displayed antioxidant activities. EVs and CDNs both did not exert immunogenicity when administered in vivo. Overall, CDNs could serve as a scalable and efficient alternative to EVs for further translation into clinical use.

Superparamagnetic Iron-Oxide Nanoparticles Synthesized via Green Chemistry for the Potential Treatment of Breast Cancer.

In the emerging field of nanomedicine, nanoparticles have been widely considered as drug carriers and are now used in various clinically approved products. Therefore, in this study, we synthesized superparamagnetic iron-oxide nanoparticles (SPIONs) via green chemistry, and the SPIONs were further coated with tamoxifen-conjugated bovine serum albumin (BSA-SPIONs-TMX). The BSA-SPIONs-TMX were within the nanometric hydrodynamic size (117 ± 4 nm), with a small poly dispersity index (0.28 ± 0.02) and zeta potential of -30.2 ± 0.09 mV. FTIR, DSC, X-RD, and elemental analysis confirmed that BSA-SPIONs-TMX were successfully prepared. The saturation magnetization (Ms) of BSA-SPIONs-TMX was found to be ~8.31 emu/g, indicating that BSA-SPIONs-TMX possess superparamagnetic properties for theragnostic applications. In addition, BSA-SPIONs-TMX were efficiently internalized into breast cancer cell lines (MCF-7 and T47D) and were effective in reducing cell proliferation of breast cancer cells, with IC50 values of 4.97 ± 0.42 µM and 6.29 ± 0.21 µM in MCF-7 and T47D cells, respectively. Furthermore, an acute toxicity study on rats confirmed that these BSA-SPIONs-TMX are safe for use in drug delivery systems. In conclusion, green synthesized superparamagnetic iron-oxide nanoparticles have the potential to be used as drug delivery carriers and may also have diagnostic applications.

Combinatorial Chemosensitive Nanomedicine Approach for the Treatment of Breast Cancer.

Breast cancer is the most commonly diagnosed type of cancer and ranks second among cancer that leads to death. From becoming the foremost reason for global concern, this multifactorial disease is being treated by conventional chemotherapies that are associated with severe side effects, with chemoresistance being the ruling reason. Exemestane, an aromatase inhibitor that has been approved by the US FDA for the treatment of breast cancer in post-menopausal women, acts by inhibiting the aromatase enzyme, in turn, inhibiting the production of estrogen. However, the clinical application of exemestane remains limited due to its poor aqueous solubility and low oral bioavailability. Furthermore, the treatment regimen of exemestane often leads to thinning of bone mineral density. Thymoquinone, a natural compound derived from the oil of the seeds of Nigella sativa Linn, possesses the dual property of being a chemosensitizer and chemotherapeutic agent. In addition, it has been found to exhibit potent bone protection properties, as evidenced by several studies. To mitigate the limitations associated with exemestane and to deliver to the cancerous cells overcoming chemoresistance, the present hypothesis has been put forth, wherein a natural chemosensitizer and chemotherapeutic agent thymoquinone will be incorporated into a lipid nanocarrier along with exemestane for combinatorial delivery to cancer cells. Additionally, thymoquinone being bone protecting will help in ousting the untoward effect of exemestane at the same time delivering it to the required malignant cells, safeguarding the healthy cells, reducing the offsite toxicity, and providing potent synergistic action.

Investigations on Cellular Uptake Mechanisms and Immunogenicity Profile of Novel Bio-Hybrid Nanovesicles.

In drug delivery, the development of nanovesicles that combine both synthetic and cellular components provides added biocompatibility and targeting specificity in comparison to conventional synthetic carriers such as liposomes. Produced through the fusion of U937 monocytes' membranes and synthetic lipids, our nano-cell vesicle technology systems (nCVTs) showed promising results as targeted cancer treatment. However, no investigation has been conducted yet on the immunogenic profile and the uptake mechanisms of nCVTs. Hence, this study was aimed at exploring the potential cytotoxicity and immune cells' activation by nCVTs, as well as the routes through which cells internalize these biohybrid systems. The endocytic pathways were selectively inhibited to establish if the presence of cellular components in nCVTs affected the internalization route in comparison to both liposomes (made up of synthetic lipids only) and nano-cellular membranes (made up of biological material only). As a result, nCVTs showed an 8-to-40-fold higher cellular internalization than liposomes within the first hour, mainly through receptor-mediated processes (i.e., clathrin- and caveolae-mediated endocytosis), and low immunostimulatory potential (as indicated by the level of IL-1α, IL-6, and TNF-α cytokines) both in vitro and in vivo. These data confirmed that nCVTs preserved surface cues from their parent U937 cells and can be rationally engineered to incorporate ligands that enhance the selective uptake and delivery toward target cells and tissues.

Investigations on detoxification mechanisms of novel para-phenylenediamine analogues through N-acetyltransferase 1 (NAT-1).

Para-phenylenediamine (PPD) is one of the most used chemicals in oxidative hair dyes. However, its use has been associated with adverse effects on health, including contact dermatitis and other systemic toxicities. Novel PPD derivatives have been proposed as a safer replacement for PPD. This can be achieved if these molecules minimally permeate the skin and/or are easily metabolised by enzymes in the skin (e.g., N-acetyltransferase-1 (NAT-1)) into innocuous compounds before gaining systemic entry. This study investigated the detoxification pathway mediated by NAT-1 enzymes on 6 synthesized PPD analogues (namely, P1-P6) with different chemical properties, to study the role of functional groups on detoxification mechanisms in HaCaT skin cells. These compounds were carefully designed with different chemical properties (whereby the ortho position of PPD was substituted by nucleophile and electrophile groups to promote N-acetylation reactions, metabolism and clearance). Compounds P2-P4 N-acetylated at 54-49 nmol/mg/min, which is 1.6 times higher than N-acetylation of PPD, upregulated NAT-1 activity from 8-7% at 50 µM to 22-11% at 100 µM and showed 4 times higher rate of elimination (k equal to 0.141 ± 0.016-0.124 ± 0.01 h-1) and 3 times faster rate of clearance (0.172 ± 0.007-0.158 ± 0.005 h-1mgprotein-1) than PPD (0.0316 ± 0.0019 h-1, 0.0576 ± 0.003 h-1mg protein-1, respectively). The data suggest that nucleophile substituted compounds detoxify at a faster rate than PPD. Our metabolic and detoxification mechanistic studies revealed significantly higher rates of N-acetylation, NAT-1 activity and higher detoxification of P2-P4 in keratinocytes, suggesting the importance of nucleophilic groups at the ortho position in PPD to reduce toxicity of aniline-based dyes on human skin cells.

Recent advances in targeted nanotherapeutic approaches for breast cancer management.

Breast cancer is the most commonly occurring tumor disease worldwide. Breast cancer is currently managed by conventional chemotherapy, which is inadequate in curbing this heterogeneous disease and results in off-site toxic effects, suggesting effective treatment approaches with better therapeutic profiles are needed. This review, therefore, focuses on the recent advancements in delivering therapeutics to the target site using passive and/or active targeted nanodrug-delivery systems to ameliorate endolysosomal escape. In addition, recent strategies in targeting breast cancer stem cells are discussed. The role of naturally cell-secreted nanovesicles (exosomes) in the management of triple-negative breast cancer is also discussed.

Lay abstract Breast cancer is the most common cancer in women around the world with a high death rate. Current treatment methods are not able to cure this disease completely. Recently, nanoparticles have been used to deliver anticancer drugs to breast cancer cells. Targeting the breast cancer stem cells (cells from which breast cancer cells develop) also shows significant results in treating this disease. Furthermore, exosomes (nanosized sac-like structures that originate from normal cells) appear to have a natural targeting ability toward triple-negative breast cancer. These topics, and more, are discussed in this review, highlighting the recent advancements made in the field of nanomedical breast cancer management.

Quercetin loaded silver nanoparticles in hydrogel matrices for diabetic wound healing.

Quercetin (QCT) is an effective antioxidant, antifibrotic and wound healing agent. Silver nanoparticles (AgNPs) are an effective antimicrobial, antifungal and wound healing agent and considered as gold standard for wound treatment especially diabetic and burn wounds. The present study aimed to investigate QCT loaded AgNPs in hydrogel matrices (QCT-AgNPs hydrogel) as synergistic treatment paradigms for diabetic wound. Quality by Design approach was employed for the optimization of hydrogel preparation using carbopol-934 andaloevera.The developed QCT-AgNPs hydrogel was characterized for hydrodynamic diameter, %entrapment efficiency (%EE), surface morphology, texture analysis,in-vitrodrug release, skin irritation study,ex-vivopermeation study (confocal study), and antimicrobial efficacy. The optimized formulation showed hydrodynamic diameter of ∼44.1 nm with smooth spherical surface morphology and ∼92.09% of QCT was entrapped in QCT-AgNPs hydrogel matrices. The antimicrobial study revealed superior therapeutic efficacy of QCT-AgNPs hydrogel in comparison to marketed (MRKT) gel onS. aureusandE. coli. Moreover,in-vivoresults demonstrated that QCT-AgNPs hydrogel significantly (p < 0.001) reduced the wound gap and increased % re-epithelialization compared with diabetic control after 18 d of post treatment in excisional diabetic wound model. In conclusion, this study opens up an avenue for the treatment of diabetic wound.

Sirolimus loaded chitosan functionalized poly (lactic-co-glycolic acid) (PLGA) nanoparticles for potential treatment of age-related macular degeneration.

The usefulness of sirolimus (SIR) in the treatment of diseases that involve retinal degeneration like age-related macular degeneration (AMD) has been well documented. However, the problem still remains probably owing to the peculiar environment of the eye and/or unfavourable physiochemical profile of SIR. In the present work, we aimed to fabricate sirolimus loaded PLGA nanoparticles (SIR-PLGA-NP) and chitosan decorated PLGA nanoparticles (SIR-CH-PLGA-NP) to be administered via non-invasive subconjunctival route. Both the nanoparticles were characterized in terms of size, zeta potential, DSC, FTIR and XRD analysis. Quality by Design (QbD) approach was employed during the preparation of nanoparticles and the presence of chitosan coating was confirmed through thermogravimetric analysis and contact angle studies. Cationic polymer modification showed sustained in-vitro SIR release and enhanced ex-vivo scleral permeation and penetration. Further, SIR-CH-PLGA-NP revealed enhanced cellular uptake and thus, reduced lipopolysaccharide (LPS)-induced free-radicals generation by RAW 264.7 cells. The prepared nanoparticles were devoid of residual solvent and were found to be safe in HET-CAM analysis, RBCs damage analysis and histopathology studies. Moreover, high anti-angiogenic potential was observed in SIR-CH-PLGA-NP compared with SIR-PLGA-NP in chorioallantoic membrane (CAM) test. Overall, the current work opens up an avenue for further investigation of CH-PLGA-NP as SIR nanocarrier in the treatment of AMD.

Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles.

Recently, bioinspired cell-derived nanovesicles (CDNs) have gained much interest in the field of nanomedicine due to the preservation of biomolecular structure characteristics derived from their parent cells, which impart CDNs with unique properties in terms of binding and uptake by target cells and intrinsic biological activities. Although the production of CDNs can be easily and reproducibly achieved with any kind of cell culture, application of CDNs for therapeutic purposes has been greatly hampered by their physical and chemical instability during long-term storage in aqueous dispersion. In the present study, we conceived a lyophilization approach that would preserve critical characteristics regarding stability (vesicles' size and protein content), structural integrity, and biological activity of CDNs for enabling long-term storage in freeze-dried form. Compared to the lyoprotectant sucrose, trehalose-lyoprotected CDNs showed significantly higher glass transition temperature and lower residual moisture content. As assessed by ATR-FTIR and far-UV circular dichroism, lyophilization in the presence of the lyoprotectant effectively maintained the secondary structure of cellular proteins. After reconstitution, lyoprotected CDNs were efficiently associated with HeLa cells, CT26 cells, and bone marrow-derived macrophages at a rate comparable to the freshly prepared CDNs. In vivo, both lyoprotected and freshly prepared CDNs, for the first time ever reported, targeted the injured heart, and exerted intrinsic cardioprotective effects within 24 h, attributable to the antioxidant capacity of CDNs in a myocardial ischemia/reperfusion injury animal model. Taken together, these results pave the way for further development of CDNs as cell-based therapeutics stabilized by lyophilization that enabled long-term storage while preserving their activity.

Extracellular vesicles in cardiovascular disease.

Cardiovascular disease remains the leading cause of morbidity and mortality globally. Extracellular vesicles (EVs), a group of heterogeneous nanosized cell-derived vesicles, have attracted great interest as liquid biopsy material for biomarker discovery in a variety of diseases including cardiovascular disease. Because EVs inherit bioactive components from parent cells and are able to transfer their contents to recipient cells, EVs hold great promise as potential cell-free therapeutics and drug delivery systems. However, the development of EV-based diagnostics, therapeutics or drug delivery systems has been challenging due to the heterogenicity of EVs in biogenesis, size and cellular origin, the lack of standardized isolation and purification methods as well as the low production yield. In this review, we will provide an overview of the recent advances in EV-based biomarker discovery, highlight the potential usefulness of EVs and EV mimetics for therapeutic treatment and drug delivery in cardiovascular disease. In view of the fast development in this field, we will also discuss the challenges of current methodologies for isolation, purification and fabrication of EVs and potential alternatives.

Gut Microbiota as an Emerging Therapeutic Avenue for the Treatment of Nonalcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of death related to liver diseases worldwide. Despite this, there is no specific treatment approved for the disease till now, which could be due to the poor understanding of the pathophysiology of this disease. In the past few decades, several scientists have speculated the root cause of NAFLD to be dysbalance in the gut microbiome resulting in a susceptibility to the inflammatory cascade in the liver. Herein, we hypothesize to fabricate a novel formulation containing prebiotic with probiotics which thereby would help in maintaining the gut homeostasis, and be used for the treatment of NAFLD. The proposed novel formulation would contain a Bifidobacterium sp. with Faecalibacterium prausnitzii in the presence of a dietary fibre having hepatoprotective activity. These two strains of probiotics would help in increasing the concentration of butyrate in the gut which in turn would inhibit intestinal inflammation and maintain gut integrity. The dietary fibre would serve a dual mechanism; firstly, it would act as a prebiotic helping in the proliferation of administered probiotics, and secondly, it would protect the liver via its own hepatoprotective action. This combinatorial approach would pave a new therapeutic avenue for the treatment of NAFLD.

Hyaluronate-functionalized hydroxyapatite nanoparticles laden with methotrexate and teriflunomide for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA), an autoimmune inflammatory disorder is currently incurable. Methotrexate and Teriflunomide are routinely prescribed drugs but their uses are limited due to severe hepatotoxicity. Hyaluronic acid (HYA) is a targeting ligand for CD44 receptors overexpressed on inflamed macrophages. The present investigation aimed at design and fabrication of HYA coated hydroxyapatite nanoparticles (HA-NPs) loaded with Methotrexate (MTX) and Teriflunomide (TEF) (HAMT-NPs) to form HYA-HAMT-NPs for the treatment of RA. HYA-HAMT-NPs showed the nanoscale size of 274.9 ± 64 nm along with a zeta potential value of -26.80 ± 6.08 mV. FTIR spectra of HYA and HYA-HAMT-NPs proved the coating of HYA on HYA-HAMT-NPs. HYA-HAMT-NPs showed less cell viability compared to drugs on RAW 264.7 macrophage cells. A biodistribution study by gamma scintigraphy imaging further strengthened the results by revealing significantly higher (p<0.05) percentage radioactivity (76.76%) of HYA-HAMT-NPs in the synovial region. The results obtained by pharmacodynamic studies ensured the better efficacy of HYA-HAMT-NPs in preventing disease progression and promoting articular regeneration. Under hepatotoxicity evaluation, liver histopathology and liver enzyme assay revealed ~29% hepatotoxicity was reduced by HYA-HAMT-NPs when compared to conventional FOLITRAX-10 and AUBAGIO oral treatments. Overall, the results suggest that HYA-HAMT-NP is a promising delivery system to avoid drug-induced hepatotoxicity in RA.

Tailoring Midazolam-Loaded Chitosan Nanoparticulate Formulation for Enhanced Brain Delivery via Intranasal Route.

In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated for enhanced transport to the brain through the intranasal (IN) route. These days, IN MDZ is very much in demand for treating life-threatening seizure emergencies; therefore, its nanoparticle formulation was formulated in the present work because it could substantially improve its brain targeting via the IN route. MDZ-loaded chitosan nanoparticles (MDZ-CSNPs) were formulated and optimized by the ionic gelation method and then evaluated for particle size, particle size distribution (PDI), drug loading (DL), encapsulation efficiency (EE), and in vitro release as well as in vitro permeation. The concentration of MDZ in the brain after the intranasal administration of MDZ-CSNPs (Cmax 423.41 ± 10.23 ng/mL, tmax 2 h, and area under the curve from 0 to 480 min (AUC0-480) of 1920.87 ng.min/mL) was found to be comparatively higher to that achieved following intravenous (IV) administration of MDZ solution (Cmax 245.44 ± 12.83 ng/mL, tmax 1 h, and AUC0-480 1208.94 ng.min/mL) and IN administration of MDZ solution (Cmax 211.67 ± 12.82, tmax 2 h, and AUC0-480 1036.78 ng.min/mL). The brain-blood ratio of MDZ-CSNPs (IN) were significantly greater at all sampling time points when compared to that of MDZ solution (IV) and MDZ (IN), which indicate that direct nose-to-brain delivery by bypassing the blood-brain barrier demonstrates superiority in brain delivery. The drug-targeting efficiency (DTE%) as well as nose-to-brain direct transport percentage (DTP%) of MDZ-CSNPs (IN) was found to be comparatively higher than that for other formulations, suggesting better brain targeting potential. Thus, the obtained results demonstrated that IN MDZ-CSNP has come up as a promising approach, which exhibits tremendous potential to mark a new landscape for the treatment of status epilepticus.

Facile functionalization of Teriflunomide-loaded nanoliposomes with Chondroitin sulphate for the treatment of Rheumatoid arthritis.

This research aims to coat Teriflunomide (TEF) loaded conventional nanoliposomes (CON-TEF-LIPO) with Chondroitin sulphate (CS) to produce CS-TEF-LIPO for the effective treatment of Rheumatoid arthritis (RA). Both CON-TEF-LIPO and CS-TEF-LIPO were produced, characterized and evaluated for their active targeting potential towards CD44 receptors. Cell cytotoxicity, cell viability and intracellular uptake study on differentiated U937 and MG-63 cells demonstrated the active targeting of CS-TEF-LIPO towards CD44 receptors. Furthermore, in vivo pharmacodynamic, biochemical, radiological and histopathological studies performed in adjuvant induced arthritic (AIA) rat model showed a significant (P < 0.05) reduction in inflammation in arthritic rat paw in CS-TEF-LIPO group compared to TEF and CON-TEF-LIPO groups. Moreover, liver toxicity study revealed that CS-TEF-LIPO showed no signs of toxicity and biodistribution study revealed the accumulation of CS-TEF-LIPO in synovial region of arthritic rat. Taken together, results suggest that CS-TEF-LIPO could provide a new insight for an effective treatment of RA.

Nanostructured lipid carrier potentiated oral delivery of raloxifene for breast cancer treatment.

Nanotherapeutics in cancer treatment are dominating global science and research, and have been recognized as the pioneering medical care regimen. Raloxifene (RLN) has been used for its anti-proliferative action on mammary tissue, however, it suffers from poor oral bioavailability. This investigation gives an account of the design and development of RLN-loaded nanostructured lipid carriers (RLN-NLCs) using a simple and scalable ultrasonication method for improved oral efficacy and limited offsite toxicity using Compritol® 888 ATO as a solid lipid and Transcutol® HP as a liquid lipid. In addition, the optimized RLN-NLCs were in the nanometric range (121 nm) with high % entrapment efficiency (%EE) (81%) for RLN, and were further freeze-dried in the presence of mannitol to enhance the stability of RLN-NLCs in the dry state for long-term use. Morphological observation under a transmission electron microscope and scanning electron microscope revealed the spherical smooth surface nanometric size of RLN-NLCs. Powder x-ray diffraction confirmed the encapsulation of RLN into the RLN-NLC's matrix with reduced crystallinity of the drug. The in vitro release study showed a burst release for an initial 4 h, and sustained release for up to 24 h. Furthermore, the RLN-NLCs showed higher cytotoxicity towards MCF-7 cells in vitro in comparison to RLN suspension, and an ex vivo intestinal permeation study demonstrated improved intestinal permeability of RLN-NLCs. Moreover, the in vivo pharmacokinetic study in female Wistar rats showed a 4.79-fold increment in oral bioavailability of RLN from RLN-NLCs compared to RLN suspension. Taken together, our results pave the way for a new nanotherapeutic approach towards breast cancer treatment.

PEGylated Nanoliposomes Potentiated Oral Combination Therapy for Effective Cancer Treatment.

The conventional treatment regimen for cancer with a single chemotherapeutic agent is far behind the clinical expectations due to the complexity of cancer biology and is also associated with poor Quality of Life (QOL) due to off-site toxicity and multidrug resistance. In recent years, nanopotentiated combination therapy has shown significant improvement in cancer treatment via a synergistic approach. However, being synthetic in nature, nanocarriers have been associated with the activation of the Complement (C) activation system resulting in serious hypersensitivity reactions known as CActivation Related Pseudoallergy (CARPA) effect once given via intravenous injection. On the other hand, nanopotentiated oral drug delivery offers several advantages for the effective and safe delivery of the drug to the target site. This hypothesis aims to put forward wherein Exemestane (chemotherapeutic agent) and lycopene (herbal bioactive) co-laden into PEGylated liposomes and delivered to the breast cancer via the oral route. PEGylation of the liposomes would prevent both molecules from the harsh microenvironment of the Gastrointestinal Tract (GIT) and would eventually promote their intestinal absorption via the lymphatic pathway to the systemic circulation. Lycopene being a potent antioxidant and anti-cancer herbal bioactive would promote the therapeutic efficacy of the Exemestane via a synergistic approach. This nanopotentiated oral combination therapy would pave the path for the safe and effective treatment of cancer.

Recent theranostic paradigms for the management of Age-related macular degeneration.

Degenerative diseases of eye like Age-related macular degeneration (AMD), that affects the central portion of the retina (macula), is one of the leading causes of blindness worldwide especially in the elderly population. It is classified mainly as wet and dry form. With expanding knowledge about the underlying pathophysiology of the disease, various treatment strategies are being employed to halt the course of the disease progression. Hitherto, there is no ideal therapy which can cure the disease completely, and targeting the posterior segment of the eye is yet another challenge. The purpose of this review is to summarize the recent advances in the management and treatment stratagems (therapies, delivery systems and diagnostic tools) pertaining to AMD viz. molecular targeting, stem cell therapy, nanotechnology and exosomes with special reference to newer technologies like artificial intelligence and 3D printing. Furthermore, the role of diet and nutritional supplements in the prevention and treatment of the disease has also been highlighted. The alarming increase in the said disorder around the globe demands exhaustive research and investigations in the treatment zone. This review thus additionally directs the attention towards the challenges and future perspectives of different treatment approaches for AMD.

Biocompatible Nanovesicular Drug Delivery Systems with Targeting Potential for Autoimmune Diseases.

Autoimmune diseases are collectively addressed as chronic conditions initiated by the loss of one's immunological tolerance, where the body treats its own cells as foreigners or self-antigens. These hay-wired antibodies or immunologically capable cells lead to a variety of disorders like rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis and recently included neurodegenerative diseases like Alzheimer's, Parkinsonism and testicular cancer triggered T-cells induced autoimmune response in testes and brain. Conventional treatments for autoimmune diseases possess several downsides due to unfavourable pharmacokinetic behaviour of drug, reflected by low bioavailability, rapid clearance, offsite toxicity, restricted targeting ability and poor therapeutic outcomes. Novel nanovesicular drug delivery systems including liposomes, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes and biologically originated exosomes have proved to possess alluring prospects in supporting the combat against autoimmune diseases. These nanovesicles have revitalized available treatment modalities as they are biocompatible, biodegradable, less immunogenic and capable of carrying high drug payloads to deliver both hydrophilic as well as lipophilic drugs to specific sites via passive or active targeting. Due to their unique surface chemistry, they can be decorated with physiological or synthetic ligands to target specific receptors overexpressed in different autoimmune diseases and can even cross the blood-brain barrier. This review presents exhaustive yet concise information on the potential of various nanovesicular systems as drug carriers in improving the overall therapeutic efficiency of the dosage regimen for various autoimmune diseases. The role of endogenous exosomes as biomarkers in the diagnosis and prognosis of autoimmune diseases along with monitoring progress of treatment will also be highlighted.