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Cancer is a life-threatening disease, contributing approximately 9.4 million deaths worldwide. To address this challenge, scientific researchers have investigated molecules that could act as speed-breakers for cancer. As an abiotic drug delivery system, liposomes can hold both hydrophilic and lipophilic drugs, which promote a controlled release, accumulate in the tumor microenvironment, and achieve elongated half-life with an enhanced safety profile. To further improve the safety and impair the off-target effect, the surface of liposomes could be modified in a way that is easily identified by cancer cells, promotes uptake, and facilitates angiogenesis. Integrins are overexpressed on cancer cells, which upon activation promote downstream cell signaling and eventually activate specific pathways, promoting cell growth, proliferation, and migration. RGD peptides are easily recognized by integrin over expressed cells. Just like a multistage rocket, ligand anchored liposomes can be selectively recognized by target cells, accumulate at the specific site, and finally, release the drug in a specific and desired way. This review highlights the role of integrin in cancer development, so gain more insights into the phenomenon of tumor initiation and survival. Since RGD is recognized by the integrin family, the fate of RGD has been demonstrated after its binding with the acceptor’s family. The role of RGD based liposomes in targeting various cancer cells is also highlighted in the paper.

The pharmacokinetics profile of active pharmaceutical ingredients (APIs) in the solid pharmaceutical dosage forms is largely dependent on the solid-state characteristics of the chemicals to understand the physicochemical properties by particle size, size distribution, surface area, solubility, stability, porosity, thermal properties, etc. The formation of salts, solvates, and polymorphs are the conventional strategies for altering the solid characteristics of pharmaceutical compounds, but they have their own limitations. Cocrystallization approach was established as an alternative method for tuning the solubility, permeability, and processability of APIs by introducing another compatible molecule/s into the crystal structure without affecting its therapeutic efficacy to successfully develop the formulation with the desired pharmacokinetic profile. In the present review, we have grossly focused on cocrystallization, particularly at different stages of development, from design to production. Furthermore, we have also discussed regulatory guidelines for pharmaceutical industries and challenges associated with the design, development and production of pharmaceutical cocrystals with commercially available cocrystal-based products.

The present study was carried out to develop cisplatin-loaded chitosan nanoparticles (CCNP) and cisplatin-loaded chitosan nanoparticle surface linked to rituximab (mAbCCNP) as targeted delivery formulations. The two formulations (CCNP and mAbCCNP) exhibited significant physicochemical properties. The zetapotential (ZP) values of CCNP and mAbCCNP were 30.50 ± 5.64 and 26.90 ± 9.09 mV, respectively; while their particle sizes were 308.10 ± 1.10 and 349.40 ± 3.20 z.d.nm, respectively. The poly dispersity index (PDI) of CCNP was 0.257 ± 0.030 (66.6% PDI), while that of mAbCCNP was 0.444 ± 0.007 (57.60% PDI). Differential scanning calorimetry (DSC) revealed that CCNP had endothermic peaks at temperatures ranging from 135.50 to 157.69 °C. A sharp exothermic peak was observed at 95.79 °C, and an endothermic peak was observed at 166.60 °C. The XRD study on CCNP and mAbCCNP revealed distinct peaks at 2θ . Four peaks at 35.38°, 37.47°, 49.29°, and 59.94° corresponded to CCNP, while three distinct peaks at 36.6°, 49.12°, and 55.08° corresponded to mAbCCNP. The in vitro release of cisplatin from nanoparticles followed zero order kinetics in both CCNP and mAbCCNP. The profile for CCNP showed 43.80% release of cisplatin in 6 h (R 2  = 0.9322), indicating linearity of release with minimal deviation. However, the release profile of mAbCCNP showed 22.52% release in 4 h (R 2  = 0.9416), indicating linearity with sustained release. In vitro cytotoxicity studies on MCF-7 ATCC human breast cancer cell line showed that CCNP exerted good cytotoxicity, with IC 50 of 4.085 ± 0.065 µg/mL. However, mAbCCNP did not elicit any cytotoxic effect. At a dose of 4.00 µg/mL cisplatin induced early apoptosis and late apoptosis, chromatin condensation, while it produced secondary necrosis at a dose of 8.00 µg/mL. Potential delivery system for cisplatin CCNP and mAbCCNP were successfully formulated. The results indicated that CCNP was a more successful formulation than mAbCCNP due to lack of specificity of rituximab against MCF-7 ATCC human breast cancer cells.

Breast cancer is conventionally treated by surgery, chemotherapy and radiation therapy followed by post operational hormonal therapy. Tamoxifen citrate is a best option to treat breast cancer because its selective estrogen receptor modulation activity. Owing to its antiestrogenic action on breast as well as uterine cells, Tamoxifen citrate shows uterine toxicity. The dose 20 mg per day of Tamoxifen citrate required to show therapeutic effect causes side effects and toxicity to vital organs such as liver, kidney and uterus. In the present study, transferrin-conjugated solid lipid nanoparticles (SLNs) were successfully prepared to enhance the active targeting of tamoxifen citrate in breast cancer. Developed formulations were evaluated for particle size, surface charge, surface morphology and in vitro dissolution studies. Developed formulations exhibited more cytotoxicity as compared to pure Tamoxifen citrate solution in time as well as concentration dependent manner on human breast cancer MCF-7 cells. Further, cell uptake and flow cytometry studies confirmed the qualitative uptake of developed D-SLN and SMD-SLN by human breast cancer MCF-7 cells. Overall, proposed study highlights that transferrin engineered nanocarriers could enhance the therapeutic response of nanomedicines for breast cancer treatment.

Parkinson’s disease (PD) is the second leading neurodegenerative disease that is characterized by severe locomotor abnormalities. Levodopa (L-DOPA) treatment has been considered a mainstay for the management of PD; however, its prolonged treatment is often associated with abnormal involuntary movements and results in L-DOPA-induced dyskinesia (LID). Although LID is encountered after chronic administration of L-DOPA, the appearance of dyskinesia after weeks or months of the L-DOPA treatment has complicated our understanding of its pathogenesis. Pathophysiology of LID is mainly associated with alteration of direct and indirect pathways of the cortico-basal ganglia-thalamic loop, which regulates normal fine motor movements. Hypersensitivity of dopamine receptors has been involved in the development of LID; moreover, these symptoms are worsened by concurrent non-dopaminergic innervations including glutamatergic, serotonergic, and peptidergic neurotransmission. The present study is focused on discussing the recent updates in molecular mechanisms and therapeutic approaches for the effective management of LID in PD patients.

The delivery of therapeutic molecules to the brain remains an unsolved problem to the researchers due to the existence of the blood–brain barrier (BBB), which halts the entry of unwanted substances to the brain. Central nervous system (CNS) disorders, mainly Parkinson’s disease, Alzheimer’s disease, schizophrenia, brain tumors, and stroke, are highly prevalent globally and are a growing concern for researchers due to restricting the delivery of pharmaceutical drugs to the brain. So effective treatment modalities are essential to combat the growing epidemic of CNS diseases. Recently, the growing attention in the field of nanotechnology has gained the faith of researchers for the delivery of therapeutics to the brain by targeting them to the specific target site. Polymeric nanoparticles (PNPs) emerge out to be an instrumental approach in drug targeting to the brain by overcoming the physiological barrier, biomedical barrier, and BBB. Preclinical discovery has shown the tremendous potential and versatility of PNPs in encapsulating several drugs and their targeting to the deepest regions of the brain, thus improving therapeutic intervention of CNS disorders. The current review will summarize advances in the development of PNPs for targeting therapeutics to the brain and the functional and molecular effects obtained in the preclinical model of most common CNS diseases. The advancement of PNPs in clinical practice and their prospect in brain targeting will also be discussed briefly.

Circular RNAs (circRNAs) are the newly uncovered class of non-coding RNAs being cognized as profound regulators of gene expression in developmental and disease biology. These are the covalently closed RNAs synthesized when the pre-mRNA transcripts undergo a back-splicing event. In recent years, circRNAs are gaining special attention in the scientific world and are no longer considered as “splicing noise” but rather structurally stable molecules having multiple biological functions including acting as miRNA sponges, protein decoys/scaffolds, and regulators of transcription and translation. Further, emerging evidence suggests that circRNAs are also differentially expressed in multiple cancers where they play oncogenic roles. In addition, circRNAs in association with miRNAs change the expression patterns of multiple transcription factors (TFs), which play important roles in cancer. Thus, the circRNA-miRNA-TFs axis is implicated in the progression or suppression of various cancer types and plays a role in cell proliferation, invasion, and metastasis. In this review article, we provide an outline of the biogenesis, localization, and functions of circRNAs specifically in cancer. Also, we highlight the regulatory function of the circRNA-miRNA-TFs axis in the progression or suppression of cancer and the targeting of this axis as a potential therapeutic approach for cancer management. We anticipate that our review will contribute to expanding the knowledge of the research community about this recent and rapidly growing field of circRNAs for further thorough investigation which will surely help in the management of deadly disease cancer.

Raloxifene is commonly used for breast cancer protection. The low bioavailability of raloxifene (2%) is the result of its low solubility and intestinal glucuronidation. The nano-lipid carriers are characterized by small particle size, biocompatibility, and sustainable properties that improve cellular uptake of the loaded drug. The aim of this study was the improvement of raloxifene bioavailability by enhancing its solubility and cellular penetration through formulation of D-α-tocopheryl polyethylene glycol 1000 succinate based transferosomes and augmenting their effect with the cationic cell-penetrating peptide transactivator of transcription of the human immunodeficiency virus. Particle size, zeta potential, and transmission electron microscope investigation of the formed nanocarriers were carried out. Ex vivo raloxifene permeation through rat skin and cell viability studies was investigated. The results of D-α-tocopheryl polyethylene glycol 1000 succinate- transactivator of transcription of the human immunodeficiency virus transferosomes showed an average vesicle size of 96.05 nm with positively charged vesicles 39.4 mV of zeta potential value. The results revealed significant (p < 0.05) enhancement of raloxifene permeation from raloxifene transferosomes- loaded film when compared with raw raloxifene film. IC50 results showed significant improvement of formulated raloxifene cytotoxicity by 1.42-fold in comparison with raw raloxifene against MCF-7 cell lines. The developed raloxifene-transferosomes are considered promising nano-lipid carriers for the enhancement delivery of raloxifene.

Naringenin (NAR), a flavonoid mainly found in citrus and grapefruits, has proven anti-cancer activities. However, the poor water solubility and low bioavailability of NAR limits its use as a therapeutic agent. The aim of this study was to develop and optimize stable naringenin nanoemulsions (NAR-NE) using a Box–Behnken experimental design to obtain a formulation with a higher efficiency. Anticancer activity of optimized NAR-NE was evaluated in A549 lung cancer cells using cell viability, flow-cytometric assays, and enzyme-linked immunosorbent assay. The stabilized nanoemulsion, which showed a spherical surface morphology, had a globule size of 85.6 ± 2.1 nm, a polydispersity index of 0.263 ± 0.02, a zeta potential of −9.6 ± 1.2 mV, and a drug content of 97.34 ± 1.3%. The NAR release from the nanoemulsion showed an initial burst release followed by a stable and controlled release for a longer period of 24 h. The nanoemulsion exhibited excellent thermodynamic and physical stability against phase separation and storage. The NAR-NE showed concentration-dependent cytotoxicity in A549 lung cancer cells, which was greater than that of free NAR. The percentage of apoptotic cells and cell cycle arrest at the G2/M and pre-G1 phases induced by NAR-NE were significantly higher than those produced by free NAR (p < 0.05). NAR-NEs were more effective than the NAR solution in reducing Bcl2 expression, while increasing pro-apoptotic Bax and caspase-3 activity. Therefore, stabilized NAR-NE could be a suitable drug delivery system to enhance the effects of NAR in the treatment of lung cancer.

Parkinson’s disease (PD) is a neurodegenerative disorder resulting in a decreased nigrostriatal availability of dopamine. Oxidative stress is one factor contributing to PD. Naringenin (NAR), a flavonoid, is a potent antioxidant shown to be beneficial in experimental PD. The clinical development of NAR has been hampered due to its low bioavailability resulting from gastrointestinal degradation, inefficient permeability, and low aqueous solubility. The objective of the present research was to formulate and characterize naringenin-loaded chitosan nanoparticles (NAR NPs) for nose-to-brain delivery. The cellular uptake, cytotoxicity, and neuroprotective effects of NAR NPs were determined using the SH-SY5Y cell line in vitro. NAR NPs were prepared using the ionic gelation method and characterized by zetasizer, transmission electron microscopy (TEM), and field emission microscopy (FESEM). The average particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and 24 h in vitro release profile were 87.6 ± 8.47 nm, 0.31 ± 0.04, 15.36 ± 2.05 mV, 91.12 ± 2.99%, and 54.80 ± 4.22%, respectively. The percentage NAR permeation through nasal mucosa from NPs was found to be 67.90 ± 0.72%. Cellular uptake of prepared NPs was confirmed by fluorescence microscopy. Neuroprotective activity of NAR NPs was evaluated through viability assays and by estimating reactive oxygen species (ROS) levels. NAR NPs showed enhanced neuroprotective ability and antioxidant effect against 6-OHDA-induced neurotoxicity in SH-SY5Y cells. However, animal studies are necessary to establish the potential of NAR NPs to be an effective carrier for the treatment of PD for nose-to-brain delivery.