Beta-carotene-Encapsulated Solid Lipid Nanoparticles (BC-SLNs) as Promising Vehicle for Cancer: an Investigative Assessment.

Beta-carotene (BC), a red-colored pigment found in plants and animals, is one of the most extensively investigated carotenoids due to its provitamin-A, antioxidant, and anticancer properties. The anticancer activity of BC through oral administration is severely affected due to its low bioavailability and oxidative degradation. The present study aimed to formulate and characterize solid lipid nanoparticles (SLNs) of BC for enhanced bioavailability and therapeutic efficacy. Beta-carotene-loaded solid lipid nanoparticles (BC-SLNs) were prepared employing different combinations of glyceryl monostearate and gelucire. The characterization studies were performed for particle size, morphology, release behavior, and stability. BC-SLNs were also studied for in vitro cytotoxicity in human breast cancer cell lines (MCF-7) and pharmacokinetic studies in Wistar rats. The cytotoxicity studies confirmed that encapsulation of BC within the lipid bilayers of nanoparticles did not affect its anticancer efficacy. An improved anticancer activity was observed in BC-SLNs as compared to the free BC. BC-SLNs enhanced the bioavailability of BC on oral administration by sustaining its release from the lipid core and prolongation of circulation time in the body. Similarly, area under the curve (AUCtotal) enhanced 1.92-times more when BC was incorporated into SLNs as compared to free BC. In conclusion, solid lipid nanoparticles could be an effective and promising strategy to improve the biopharmaceutical properties of carotenoids for anticancer effects.

Lycopene loaded whey protein isolate nanoparticles: An innovative endeavor for enhanced bioavailability of lycopene and anti-cancer activity.

The work entails a novel strategy of formulating the lycopene loaded whey protein isolate nanoparticles (LYC-WPI-NPs) solely using the rational blend of biomacromolecule without using equipment-intensive techniques. The LYC-WPI-NPs were fabricated as a substantial drug delivery platform, with maximum entrapment, spatial and controlled release manners, exceptional plasma concentration, and perspective for discrepancy delivery of therapeutics. Prepared nano-formulations were measured in ultra-fine size (100-350 nm) with sphere-shaped. The percent lycopene entrapment of prepared LYC-WPI-NPs was estimated in the range to 50 and 65%. In vitro percent cumulative release study demonstrated deaden and extended release i.e. approximately 75% following 16th h. The in vitro percent cell survival (cytotoxicity study) of prepared nanoparticles was evaluated against MCF-7 breast cancer cells by MTT based colorimetric assay. Sub-cellular localization of lycopene when delivered by LYC-WPI-NPs was assessed by HPLC (high performance liquid chromatography). The WPI-NPs enhance the oral bioavailability of lycopene by controlling its release from nano-formulation and facilitating its absorption through lymphatic pathways. Prophylactic anticancer efficacy of LYC-WPI-NPs was evaluated thereafter on experimentally induced breast cancer animal model. Conclusively, it may quite reasonable that lycopene loaded protein nanoparticles are competent to improve the biopharmaceutical attributes of lycopene and demonstrated prophylactic anticancer activity, decrease tumor proliferation and increase the survival rate of treated animals, thus signifying their feasible usefulness in cancer therapeutic and intervention.

Administration of antioxidants in cancer: debate of the decade.

Several randomized clinical trials have divulged that administration of antioxidants during chemotherapy decreases the effectiveness of treatment. Hence, the characteristic feature of this article is extensive assessment of putative benefits and potential risks of natural and synthetic antioxidant supplementation, administered with chemotherapy, based upon the available preclinical and clinical data. After analyzing mixed results, it was concluded that current FDA guidelines should be followed before supplementing antioxidants during cytotoxic treatment. Nevertheless, contradictory experimental animal models opposing human clinical trials discourage the concurrent administration of antioxidants ostensibly owing to the possibility of tumor protection and reduced survival.

Beta carotene-loaded zein nanoparticles to improve the biopharmaceutical attributes and to abolish the toxicity of methotrexate: a preclinical study for breast cancer.

Beta carotene (ßC) loaded nanoparticles of zein (ßC-NPs) were developed using modified phase separation technique. ßC-NPs were prepared using different zein concentration and optimized formulation was selected on the basis of micromeritics properties and entrapment efficiency. Further, ßC-NPs were evaluated for in vitro release, in vitro cell-survival, cellular localization and apoptosis induced in MCF-7 cells. The combined effect of the ßC and its nanoparticulate counterpart with MTX was evaluated thereafter for cytotoxicity and apoptotic activity in MCF-7 cells. In comparison to free ßC, the ßC-NPs demonstrated noteworthy improvement in various biopharmaceutical attributes viz Cmax (∼2.3-folds), AUCtotal (2.7-folds), t1/2 (∼1.5 folds) and MRT (∼1.5 folds), further indicating the remarkable increment in oral bioavailability of ßC after incorporation in zein nanoparticles. The anti-tumour potential of prepared ßC-NPs and effects of free ßC and ßC-NPs were investigated upon anticancer efficacy of methotrexate (MTX) in experimentally induced breast cancer rat model. Protective role of ßC on MTX-associated hepatic toxicity in wistar rats was also determined using haematological and histopathological approaches. In a nutshell, zein nanoparticles improved the cellular uptake, cytotoxicity and exhibited enhanced oral biopharmaceutical performance of ßC. This combination regimen could also be promising platform to facilitate the therapeutic benefits of anticancer agents.

Recent advances in galactose-engineered nanocarriers for the site-specific delivery of siRNA and anticancer drugs.

Galactosylated nanocarriers have recently emerged as viable and versatile tools to deliver drugs at an optimal rate specifically to their target tissues or cells, thus maximizing their therapeutic benefits while circumventing off-target effects. The abundance of lectin receptors on cell surfaces makes the galactosylated carriers suitable for the targeted delivery of bioactives. Additionally, tethering of galactose (GAL) to various carriers, including micelles, liposomes, and nanoparticles (NPs), might also be appropriate for drug delivery. Here, we review recent advances in the development of galactosylated nanocarriers for active tumor targeting. We also provide a brief overview of the targeting mechanisms and cell receptor theory involved in the ligand-receptor-mediated delivery of drug carriers.

Lanolin-based organogel of salicylic acid: evidences of better dermatokinetic profile in imiquimod-induced keratolytic therapy in BALB/c mice model.

The primary aim of the present study was to develop lanolin-based organogel with enhanced delivery potential and reduced skin irritation for the treatment of hyperkeratotic lesions and scaling. The drug was encapsulated in the lipidic bilayers of organogel. The values of particle size, polydispersity index (PDI), and zeta potential of the developed carrier system was found to be 257.5 nm, 0.272, and -24.9 mV, respectively. The system was pseudoplastic in nature with the yield value of 2.3078 Pa. The skin permeation studies exhibited superiority of the prepared lanolin-based organogel formulation over the conventional gel formulation (CGF). Further, the dermatokinetic studies also confirmed better permeation and enhanced skin bioavailability of SA to epidermis as well as dermis vis-à-vis the CGF. In conclusion, the developed organogel system not only improved the delivery profile of SA but also reduced the skin irritant potential. The current findings can provide a suitable alternative for the development of an effective topical formulation of SA for the treatment of hyperkeratotic lesions.

Methotrexate and beta-carotene loaded-lipid polymer hybrid nanoparticles: a preclinical study for breast cancer.

AIM: This work was intended to investigate the targeting potential of fructose-tethered lipid-polymeric hybrid nanoparticles (F-BC-MTX-LPHNPs) co-loaded with beta carotene (BC) and methotrexate (MTX) in breast cancer therapeutics and find out the possible protective role of BC on MTX-induced toxicity. MATERIALS & METHODS: F-BC-MTX-LPHNPs were fabricated using self-assembled nano-precipitation technique. Fructose was conjugated on the surface of the particles. The in vitro cytotoxicity, sub-cellular localization and apoptotic activity of F-BC-MTX-LPHNPs were evaluated against MCF-7 breast cancer cells. The antitumor potential of F-BC-MTX-LPHNPs was further studied. RESULTS & CONCLUSION: Outcomes suggested that F-BC-MTX-LPHNPs induced the highest apoptosis index (0.89) against MCF-7 cells. Following 30 days of treatment, the residual tumor progression was assessed to be approximately 32%, in animals treated with F-BC-MTX-LPHNPs. F-BC-MTX-LPHNPs are competent to selectively convey the chemotherapeutic agent to the breast cancers. Beta carotene ameliorated MTX-induced hepatic and renal toxicity.

Functionalized Lipid-Polymer Hybrid Nanoparticles Mediated Codelivery of Methotrexate and Aceclofenac: A Synergistic Effect in Breast Cancer with Improved Pharmacokinetics Attributes.

The present study was aimed to coencapsulate methotrexate (MTX) and aceclofenac (ACL) in fucose anchored lipid-polymer hybrid nanoparticles (Fu-LPHNPs) to achieve target specific and controlled delivery for developing therapeutic interventions against breast cancer. The effective combination therapy requires coadministration of drugs to achieve synergistic effect on tumor with minimum adverse effects. Present study investigates the potential of codelivery of MTX and ACL through LPHNPs in MCF-7 and triple negative breast cancer cells (MDA-MB-231). We obtained LPHNPs in the nanosize range (<150 nm) with better particle size distribution (<0.3). The entrapment and loading efficiency of MTX and ACL was calculated as 85-90% and 10-12%, respectively. The coumarin-6 LPHNP formulations showed rapid internalization within 2 h incubation with MCF-7 and MDA-MB-231 cells. With 8-10 times, greater bioavailability of drug-loaded LPHNPs than free MTX and ACL was obtained. Also, antitumor efficacy of MTX- and ACL-loaded LPHNPs was determined on DMBA-induced experimental breast cancer mouse model. This model showed better control over tumor growth with MTX- and ACL-loaded LPHNPs than the combination of MTX and ACL or MTX alone. ACL-loaded LPHNPs showed prophylactic and anticancer activity in DMBA-induced mouse model at higher dose (10 mg/kg). ACL-LPHNPs confer synergistic anticancer effect when administered in combination with MTX. In conclusion, ACL enhances the therapeutic and anticancer efficacy of MTX, when coencapsulated into fucose-anchored LPHNPs, as confirmed by cell viability and serum angiogenesis (IL-6, TNF-α, IL-1ß, COX2, and MMP1) at both transcript and proteome level.

Fabrication and functional attributes of lipidic nanoconstructs of lycopene: An innovative endeavour for enhanced cytotoxicity in MCF-7 breast cancer cells.

The present study investigates the anticancer efficacy of lycopene loaded lipidic nanostructured particles. With a homogenization-evaporation technique, lycopene loaded solid lipid nanoparticles (LYC-SLNs) were fabricated with different ratios of biocompatible viz. compritol ATO 888 and gelucire, and evaluated for their micromeretics properties, in vitro release, in vitro cytotoxicity, cellular uptake and apoptosis induced in MCF-7 cells. Effects of anticancer potential of LYC-SLNs on the efficacy of methotrexate (MTX), a well-established anticancer agent, was evaluated thereafter. Cell culture experiments revealed a considerably higher cellular uptake of LYC-SLNs in MCF-7 cells, as compared to the free LYC. The concentration and time dependent cell survival of MCF-7 cells was significantly reduced by LYC-SLNs, as compared to their free LYC counterparts. Additionally, the combined cytotoxicity of the LYC and its nanostructured formulation with MTX was evaluated. The results of cytotoxicity and apoptotic study revealed synergism at all-time points up to 48h. In a nutshell, the combination regimen could be promising approach to improve the therapeutic benefits of anticancer agents.

Fucose decorated solid-lipid nanocarriers mediate efficient delivery of methotrexate in breast cancer therapeutics.

The present study is designed to engineer fucose anchored methotrexate loaded solid lipid nanoparticles (SLNs) to target breast cancer. The developed nano-carriers were characterized with respect to particle size, PDI, zeta potential, drug loading and entrapment, in-vitro release etc. The characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, biodistribution, changes in tumor volume and animal survival. The ex-vivo results showed greater cellular uptake and better cytotoxicity at lower IC50 of methotrexate in breast cancer cells. Further, we observed increased programmed cell death (apoptosis) with altered lysosomal membrane permeability and better rate of degradation of lysosomal membrane in-vitro. On the other hand, in-vivo evaluation showed maximum bioavailability and tumor targeting efficiency with minimum secondary drug distribution in various organs with formulated and anchored nano-carrier when compared with free drug. Moreover, sizeable reduction in tumor burden was estimated with fucose decorated SLNs as compared to that seen with free MTX and SLNs-MTX. Fucose decorated SLNs showed promising results to develop therapeutic interventions for breast cancer, and paved a way to explore this promising and novel nano-carrier which enables to address breast cancer.

Nano-constructed Carriers Loaded With Antioxidant: Boon For Cardiovascular System.

In the last couple of decades antioxidant agents have entered the health market as an easy and attractive means of managing diseases. These agents are of enormous interest for an increasingly health-concerned society, and may be particularly relevant for prophylaxis of a number of diseases i.e. arthritis, cancer, metabolic and cardiovascular diseases, osteoporosis, cataracts, brain disorders, etc. Antioxidants are also favorable to vascular healthiness and symbolize useful compounds because they are able to diminish overall cardiovascular risk by acting analogous to first line therapy or as adjuvants in case of failure or in situations where first line therapy cannot be used. Furthermore, well-designed trials are indeed needed to improve the therapeutic efficacy and health benefits of antioxidants. Numerous in vivo proof-of-concepts studies are offered to underline the feasibility of nanostructure system in order to optimizing the delivery of cardiovascular drugs. The present review highlights the recent approaches for management of cardiovascular disease using different vesicular and particulate carriers, including liposomes, nanoparticles, and nanoemulsions, with a primary emphasis on those which are expected to enhance the antioxidants level.

Galactose engineered solid lipid nanoparticles for targeted delivery of doxorubicin.

The present investigation reports the preparation, optimization, and characterization of surface engineered solid lipid nanoparticles (SLNs) encapsulated with doxorubicin (DOX). Salient features such as biocompatibility, controlled release, target competency, potential of penetration, improved physical stability, low cost and ease of scaling-up make SLNs viable alternative to liposomes for effective drug delivery. Galactosylation of SLNs instructs some gratifying characteristic, which leads to the evolution of promising delivery vehicles. The impendence of lectin receptors on different cell surfaces makes the galactosylated carriers admirable for targeted delivery of drugs to ameliorate their therapeutic index. Active participation of some lectin receptors in immune responses to antigen overlaid the application of galactosylated carriers in delivery of antigen and immunotherapy for treatment of maladies like cancer. These advantages revealed the promising potential of galactosylated carriers in each perspective of drug delivery. The developed DOX loaded galactosylated SLNs formulation was found to have particle size 239 ± 2.40 nm, PDI 0.307 ± 0.004, entrapment efficiency 72.3 ± 0.9%. Higher cellular uptake, cytotoxicity, and nuclear localization of galactosylated SLNs against A549 cells revealed higher efficiency of the formulation. In a nutshell, the galactosylation strategy with SLNs could be a promising approach in improving the delivery of DOX for cancer therapy.

Surface engineered polymeric nanocarriers mediate the delivery of transferrin-methotrexate conjugates for an improved understanding of brain cancer.

The objective of present study was to enhance permeation of bioactive molecules across blood brain barrier (BBB) through polysorbate 80 coated poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with methotrexate-transferrin (Tw-Mtx-Tf-NP) conjugates (Mtx-Tf). The easy trans-BBB migration of developed formulations through endocytosis, and inhibition of P-gp efflux pump present in brain were established by Pluronic F-68 and/or polysorbate 80 (Tween 80/Tw). The over-expression of transferrin (Tf) receptors on cancer cell surface allowed targeted and sustained delivery of Mtx-Tf conjugated to brain cancer cells by receptor mediated endocytosis. The developed formulations showed improved penetration in comparison to non-targeting experimental NP controls. The transportation potential and bio-distribution studies of such nanosized polymeric carriers showing successful migration and trans-BBB passage was carried out by administering FITC labeled drug loaded NPs to albino rats through intravenous route. We have validated anti-tumor efficiency of newly formulated and drug loaded NPs compared to controls in experimentally induced tumor-harboring rat model. The present study suggests greater compatibility, less organ toxicity and higher anti-tumor activity of developed formulations due to their targeting and sustained delivery potential in cancer therapeutic interventions. In conclusion, our findings of targeted and sustained drug delivery potential of NPs for are corroborated with in vitro and in vivo evidence, and formulated novel delivery vehicle shows its value in developing new tools for treating brain cancer.

Mannosylated solid lipid nanoparticles as vectors for site-specific delivery of an anti-cancer drug.

The purpose of the present study was to investigate the tumor targeting potential of surface tailored solid lipid nanoparticles (SLNs) loaded with an anti-cancer drug doxorubicin HCl (DOX). DOX encapsulating SLNs were prepared, characterized and further mannosylated. The developed formulations were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), particle size/polydispersity index and zeta-potential analysis. The formulations were evaluated for in vitro drug release and hemolytic toxicity. The ex vivo cytotoxicity and cellular uptake studies were performed on A549 cell lines. In vivo studies were conducted to determine pharmacokinetics, tissue distribution pattern and nephrotoxic/hepatotoxic effect of mannosylated SLNs. In vitro, the formulations exhibited a biphasic pattern characterized by initial rapid release of the drug followed by rather slow and prolonged release. Further, the in vitro studies depicted mannose-conjugated SLNs to be least hemolytic and suitable for sustained drug delivery. Mannosylated SLNs were most cytotoxic and were preferably taken up A549 tumor cells as evaluated against uncoated SLNs and plain DOX. Pharmacokinetic studies revealed improved bioavailability, half life and mean residence time of DOX upon mannose conjugation. The biodistribution pattern exhibited that mannosylated SLNs were able to deliver a higher concentration of DOX in the tumor mass. They were also proficient to circumvent damage to renal as well as hepatic tissues. It may therefore be interpreted that mannosylated SLNs are capable to ferry bioactives selectively and specifically to the tumor sites with the interception of minimal side effects, thereby suggesting their potential application in cancer chemotherapy.