Cancer is a class of disorder characterized by anomalous growth of cells escalating in an uncontrolled way. Among all the cancers, treatment of cancerous brain tumors has been a tough challenge for the research scientists. Moreover, the absence of early-stage symptoms delays its diagnosis, consequently worsening its severity. Conventional treatments such as surgery, radiation, and chemotherapy are still linked with several limitations. The therapeutic effect of most of the anticancer drugs is highly restricted by their inability to pass the blood–brain barrier, low solubility, limited therapeutic window, and so on. Alarming incidences of brain cases associated with low survival rate across the globe coupled with the inefficiency of current treatment strategies have forced the formulation scientists to investigate nanotechnology-based advanced therapeutic approaches to tackle the disease. Various nanoplatforms such as polymeric nanoparticles (NPs), nanoliposomes, dendrimers, carbon nanotubes, and magnetic NPs have been reported in the past years to improve the drug administration into brain tumor cells and to minimize their off-target distribution for lesser side effects and better treatment outcomes. The review presents updated information on the nanocarrier-based drug delivery systems reported in the past few years for the treatment of brain tumor along with new advancements in this field. It also throws some light on the recent challenges faced in the practical field for the successful clinical translation of such nanodrug carriers along with a discussion on the future prospects.

The study explores anticancer potential of telmisartan (TS) loaded lipid nanocarriers (TLNs) in glioma cells as a potential repurposing nanomodality along with estimation of drug availability at rat brain. Experimental TLNs were produced by previously reported method and characterized. In vitro anticancer efficacy of experimental TLNs was estimated by MTT, confocal microscopy, and FACs analysis in glioma cells. Plasma and brain pharmacokinetic (PK) parameters were also analysed by LCMS/MS. Spherical, nanosized, homogenous, unilamellar, TLNs were reported having desirable drug loading (9.5% ± 0.6%), negative zeta potential and sustained TS release tendency. FITC-TLNs were sufficiently internalized into U87MG cells line within 0.5 h incubation period. IC₅₀ for TLNs was considerably higher than free TS in the tested glioma cell lines. Further, TLNs induced superior apoptotic effect in U87MG cells than TS. PK (plasma/brain) data depicted higher AUC, V _ss, MRT with lower Cl_t for TLNs suggesting improved bioavailability, in vivo residence and sustained drug availability than free TS administration. Docking studies rationalized in vitro/in vivo results as preferably higher binding affinity (docking score:12.4) was detected for TS with glioma proteins. Further, in vivo studies in glioma bearing xenograft model is underway for futuristic clinical validation of TLNs.

This study aimed to deliver a potential water-soluble antiviral drug (sofosbuvir) through optimized vesicular lipid nanocarriers (LNs) to the rat brain as a novel strategy against viral meningitis. A 2³ factorial design approach was established to assess the effect of formulation composition and process variables on the physicochemical properties of the LNs. Sofosbuvir-loaded LNs (SLNs) were developed by lipid layer hydration method utilizing optimized parameters and evaluated for various in vitro characterizations like FTIR, DSC, XRD, FESEM, vesicle size, zeta potential, drug carrying capacity and drug release. Plasma and brain pharmacokinetic (PK) studies were conducted in Sprague-Dawley rats. FTIR data depicted the absence of any major interaction between the drug and the excipients. DSC revealed a sharp endothermic peak for the drug. XRD showed the amorphic nature of the SLNs. Optimized SLNs were spherical as depicted from FESEM with 42.43 nm size, −49.21 mV zeta potential, 8.31% drug loading and sustained drug release in vitro. Plasma/brain PK studies depicted significant improvement in key PK parameters, viz. AUC, AUMC, MRT, and V_d, compared to those for the free drug. A more than 3.5-fold increase in MRT was observed for optimized SLNs (11.2 h) in brain tissue compared to the free drug (3.7 h). Ex vivo hemolysis data confirmed the non-toxic nature of the SLNs to human red blood cells. In silico docking study further confirmed strong interaction between the drug and selected protein 4YXP (herpes simplex) with docking score of −7.5 and 7EWQ protein (mumps virus) with docking score of −7.3. The optimized SLNs may be taken for further in vivo studies to pave the way towards clinical translation.

Among primary brain tumors, glioma has one of the highest fatality rates. Routine chemotherapy often faces off-target drug loss and sub-optimal drug availability at brain tissue. The present study aims at the development of transferrin-conjugated gemcitabine loaded poly (lactic co glycolic acid) nanoparticles (Tf-GB-PLGA-NPs) targeted strategy for brain cancer cell. GB-PLGA-NPs were prepared using solvent evaporation and nanoprecipitation method and then conjugated with Tf. The formulation was characterized for physicochemical parameters, in-vitro release, cytotoxicity, apoptosis (U87MG cell line), and in-vivo pharmacokinetic study. Tf-GB-PLGA-NPs showed 143±6.23 nm of particle size, 0.213 of PDI, –25 mV of zeta potential, and 77.53±1.43% of entrapment efficiency, respectively. Tf-GB-PLGA-NPs exhibited spherical morphology and sustained release of GB (76.54±4.08%) over 24 h. Tf-GB-PLGA-NPs exhibited significant (p < 0.05) cell inhibition against cell line (U87MG) than GB-PLGA-NPs and pure GB. The Tf-GB-PLGA-NPs exhibited higher U87MG apoptosis (61.25%) than GB-PLGA-NPs (31.61%). The Tf-GB-PLGA-NPs exhibited a significantly higher concentration in the brain than pure GB and GB-PLGA-NPs. Tf-GB-PLGA-NPs showed 11.16-fold higher AUC0-t (bioavailability) than pure GB solution and 2.23-fold higher bioavailability than GB-PLGA-NPs. The finding concludes that the Tf-GB-PLGA-NPs are an alternative potent carrier for GB to brain delivery for treating brain cancer.

Background: Breast cancer remains a leading cause of cancer-related mortality in women globally. The main purpose of the research to develop, optimise and characterise a trastuzumab (TZ)-functionalized nanolipid carrier (NCs) encapsulating capecitabine, as a targeted strategy to breast cancer cells, to enhance therapeutic efficacy and reduce the severe side effects associated with conventional chemotherapy. Methods: Capecitabine encapsulated NCs (CBNCs) were prepared by thin-film hydration technique, optimized by Box-Behnken design. The optimized formulation CBNCs were subsequently conjugated with TZ by using EDC-NHS chemistry. The prepared formulations of NCs were evaluated by FTIR, DSC, XRD, FESEM, TEM, AFM, drug loading, entrapment efficiency, average particle size, PDI, zeta potential, in vitro drug release. The successful surface conjugation of TZ was tested by BCA assay and SDS-PAGE analysis. In vitro targeting efficiency and cytotoxicity initially tested in MCF-7 cells (HER2-low expressing) and subsequently validated in SKBR3 cells (HER2-overexpressing) to confirm receptor-mediated uptake and specificity. Results: Optimized CBNCs were found spherical, nanosized (194.6 nm), with a zeta potential − 25.55 mV for CBNCs, which increased to – 57.76 mV upon TZ conjugation. The formulation showed 8.5% drug loading capacity and 84.26% drug release over 72 h. FTIR and DSC showed compatibility of drug and lipid components with no major shifting in characteristic peaks. TEM and AFM confirmed formation of stable, spherical discrete nanostructures. TZ conjugation showed minor alternation in average size/surface charge/morphology/texture. Successful TZ conjugation onto CBNCs was confirmed by BCA assay and SDS-PAGE. Fluorescence microscopy confirmed successful cellular internalization. MTT assay on SKBR3 cells demonstrated significantly higher cytotoxicity for TZ-CBNCs compared to CBNCs and free drug, thereby validating the HER2-specific targeting effect beyond preliminary results obtained in MCF-7 cells. Conclusion: In view of the desired physicochemical properties, controlled drug release, and in vitro anticancer effectiveness, further in vivo investigations should be prioritized to validate its clinical application in HER2-positive breast cancer treatment. Nonetheless, the use of HER2-low MCF-7 cells in early assays highlights the importance of complementary validation in HER2-overexpressing models, as addressed by SKBR3 testing in this study.