Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles.

Keratinocyte-derived carcinomas, including squamous cell carcinoma (SCC), comprise the most common malignancies. Surgical excision is the therapeutic standard but is not always clinically feasible, and currently available alternatives are limited to superficial tumors. To address the need for a nonsurgical treatment for nodular skin cancers like SCC, we developed a bioadhesive nanoparticle (BNP) drug delivery system composed of biodegradable polymer, poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG), encapsulating camptothecin (CPT). Nanoparticles (NPs) of PLA-HPG are nonadhesive NPs (NNPs), which are stealthy in their native state, but we have previously shown that conversion of the vicinal diols of HPG to aldehydes conferred NPs the ability to form strong covalent bonds with amine-rich surfaces. Herein, we show that these BNPs have significantly enhanced binding to SCC tumor cell surfaces and matrix proteins, thereby significantly enhancing the therapeutic efficacy of intratumoral drug delivery. Tumor injection of BNP-CPT resulted in tumor retention of CPT at ∼50% at 10 d postinjection, while CPT was undetectable in NNP-CPT or free (intralipid) CPT-injected tumors at that time. BNP-CPT also significantly reduced tumor burden, with a portion (∼20%) of BNP-CPT-treated established tumors showing histologic cure. Larger, more fully established PDV SCC tumors treated with a combination of BNP-CPT and immunostimulating CpG oligodeoxynucleotides exhibited enhanced survival relative to controls, revealing the potential for BNP delivery to be used along with local tumor immunotherapy. Taken together, these results indicate that percutaneous delivery of a chemotherapeutic agent via BNPs, with or without adjuvant immunostimulation, represents a viable, nonsurgical alternative for treating cutaneous malignancy.

Decursin and decursinol angelate: molecular mechanism and therapeutic potential in inflammatory diseases.

Epidemiological studies have shown that inflammation plays a critical role in the development and progression of various chronic diseases, including cancers, neurological diseases, hepatic fibrosis, diabetic retinopathy, and vascular diseases. Decursin and decursinol angelate (DA) are pyranocoumarin compounds obtained from the roots of Angelica gigas. Several studies have described the anti-inflammatory effects of decursin and DA. Decursin and DA have shown potential anti-inflammatory activity by modulating growth factors such as vascular endothelial growth factor, transcription factors such as signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells, cellular enzymes including matrix metalloproteinases cyclooxygenase, and protein kinases such as extracellular receptor kinase, phosphatidylinositol-3-kinase, and protein kinase C. These compounds have the ability to induce apoptosis by activating pro-apoptotic proteins and the caspase cascade, and reduced the expression of anti-apoptotic proteins such as B-cell lymphoma 2 and B-cell lymphoma-extra-large. Interaction with multiple molecular targets and cytotoxic effects, these two compounds are favorable candidates for treating various chronic inflammatory diseases such as cancers (prostate, breast, leukemia, cervical, and myeloma), rheumatoid arthritis, diabetic retinopathy, hepatic fibrosis, osteoclastogenesis, allergy, and Alzheimer's disease. We have summarized the preliminary studies regarding the biological effects of decursin and DA. In this review, we will also highlight the functions of coumarin compounds that can be translated to a clinical practice for the treatment and prevention of various inflammatory ailments.

Therapeutic potential of curcumin for multiple sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS), characterized by demyelination, neuronal injury, and breaching of the blood-brain barrier (BBB). Epidemiological studies have shown that immunological, genetic, and environmental factors contribute to the progression and development of MS. T helper 17 (Th17) cells are crucial immunological participant in the pathophysiology of MS. The aberrant production of IL-17 and IL-22 by Th17 cells crosses BBB promotes its disruption and interferes with transmission of nerve signals through activation of neuroinflammation in the CNS. These inflammatory responses promote demyelination through transcriptional activation of signal transducers and activators of transcription-1 (STAT-1), nuclear factor kappa-B (NF-κB), matrix metalloproteinases (MMPs), interferon ϒ (IFNϒ), and Src homology region 2 domain-containing phosphatase-1 (SHP-1). B cells also contribute to disease progression through abnormal regulation of antibodies, cytokines, and antigen presentation. Additionally, oxidative stress has been known as a causative agent for the MS. Curcumin is a hydrophobic yellowish diphenolic component of turmeric, which can interact and modulate multiple cell signaling pathways and prevent the development of various autoimmune neurological diseases including MS. Studies have reported curcumin as a potent anti-inflammatory, antioxidant agent that could modulate cell cycle regulatory proteins, enzymes, cytokines, and transcription factors in CNS-related disorders including MS. The current study summarizes the reported knowledge on therapeutic potential of curcumin against MS, with future indication as neuroprotective and neuropharmacological drug.

Camptothecin-loaded mesoporous silica nanoparticles functionalized with CpG oligodeoxynucleotide as a new approach for skin cancer treatment.

The therapeutic efficacy of camptothecin (CPT), a potent antitumor alkaloid, is hindered by its hydrophobic nature and instability, limiting its clinical use in treating cutaneous squamous cell carcinoma (SCC). This study introduces a novel nano drug delivery system (NDDS) utilizing functionalized mesoporous silica nanoparticles (FMSNs) for efficient CPT delivery. The FMSNs were loaded with CPT and subsequently coated with chitosan (CS) for enhanced stability and bioadhesion. Importantly, CpG oligodeoxynucleotide (CpG ODN) was attached onto the CS-coated FMSNs to leverage the immunostimulatory properties of CpG ODN, augmenting the chemotherapy's efficacy. The final formulation FMSN-CPT-CS-CpG displayed an average size of 241 nm and PDI of 0.316 with an encapsulation efficiency of 95 %. Comprehensive in vitro and in vivo analyses, including B16F10 cells and DMBA/TPA-induced SCC murine model, demonstrated that the FMSN-CPT-CS-CpG formulation significantly enhanced cytotoxicity against B16F10 cells and induced complete regression in 40 % of the in vivo subjects, surpassing the efficacy of standard CPT and FMSN-CPT treatments. This study highlights the potential of combining chemotherapeutic and immunotherapeutic agents in an NDDS for targeted, efficient skin cancer treatment.

Synthesis, characterization and antibacterial activity of silver nanoparticles using Rhazya stricta.

BACKGROUND: Green synthesis of metallic nanoparticles has gained significant attention in the field of nanomedicine as an environment-friendly and cost-effective alternative in comparison with other physical and chemical methods. Several metals such as silver, gold, iron, titanium, zinc, magnesium and copper have been subjected to nanoformulation for a wide range of useful applications. Silver nanoparticles (AgNPs) are playing a major role in the field of nanomedicine and nanotechnology. They are widely used in diagnostics, therapeutic and pharmaceutical industries. Studies have shown potential inhibitory antimicrobial, anti-inflammatory and antiangiogenesis activities of AgNPs. METHODS: AgNPs have been synthesized using silver nitrate and methanolic root extract of Rhazya stricta that belongs to the Apocynaceae family. Stability and dispersion of nanoparticles were improved by adding xylitol. Synthesized nanoparticles were characterized by UV-Vis spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, X-ray diffractometer and Fourier transforms infrared spectroscopy. Furthermore, the antibacterial effect of the plant extract and the nanoparticles were evaluated against gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacteria. RESULTS: The average size of AgNPs synthesized, was 20 nm with the spherical shape. Rhazya stricta based nanoparticles exhibited improved antibacterial activity against both gram-positive and negative strains.

Multifunctional Curcumin Mediate Multitherapeutic Effects.

Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases. Numerous studies have shown that curcumin modulate multiple molecular targets and can be translated to the clinics for multiple therapeutic processes. There is compelling evidence that curcumin can block cell proliferation, invasion, and angiogenesis as well as reduced the prolonged survival of cancer cells. Curcumin mediates anti-inflammatory effect through downregulation of inflammatory cytokines, transcription factors, protein kinases, and enzymes that promote inflammation and development of chronic diseases. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways by activating caspase cascades. Curcumin is a safe and nontoxic drug that has been reported to be well tolerated. Available clinical trials support the potential role of curcumin for treatment of various inflammatory disorders. However, curcumin's efficacy is hindered by poor absorption and low bioavailability, which limit its translation into clinics. This review outlines the potential pharmacological and clinical role of curcumin, which provide a gateway for the beneficial role of plant isolated compounds in treatment of various inflammatory diseases and cancer.