Nanocarriers and Diabetes: New Vistas and the Way Ahead.

World Health Organization has reported an estimated 1.5 million deaths directly due to diabetes in 2019. Center for Disease Control and Prevention, in its National Diabetes Statistics Report, 2020, says that 1 in 10 United States residents has diabetes. This rapid progression of diabetes is noteworthy despite significant advances in the field of antidiabetic medicine. The critical challenges in treatment are dyslipidemia, hyperinsulinemia, and hyperglycemia. The latest research has also linked diabetes to carcinogenesis. The diabetic condition accelerates cell growth, proliferation, migration, inflammation, angiogenesis, metastasis, and inhibition of apoptosis in cancer cells. In addition, diabetic complications of nephropathy, retinopathy, neuropathy, cardiomyopathy, peripheral arterial disease, coronary artery disease, and stroke increase morbidity. Amidst all these challenges, a ray of hope is the advent of nanocarriers. The nano size helps in the targeted and controlled delivery of drugs. In addition, nanocarrier formulation helps in the delivery of acid-labile and enzyme- labile molecules and plant-based macromolecules via the oral route. Its use in the form of dendrimers, ethosomes, niosomes, transfersomes, and polymeric nanoparticles is established. In addition, different polymers used to formulate nanocarriers are also established for targeting diabetes. Thus, this review aims to compile approaches involving the use of nanocarriers for the betterment of pharmacotherapy of diabetes and to provide a way ahead for researchers in the field.

Celiac disease: Pathogenesis, disease management and new insights into the herbal-based treatments.

Celiac disease (CD) is a gluten intolerance autoimmune disorder which its symptoms involve the gastrointestinal tract and sometimes the other organs. It is one of the most prevalent health problems rising in many populations as statistics show that in every 100 people about one person is suffering from CD. It has been observed that the persons who genetically contain the human leukocyte antigen (HLA) DQ2 and HLA DQ8 genes involved in the immune system haplotypes are more prone to develop an allergy to gluten. The only treatment currently available for CD is a strict gluten-free diet. However, recent research has shown promising new insights into the herbal-based treatments of CD. New insight on CD is now offering various prospects to manage its treatment, diagnosis, and serving in the development of advanced therapies. Several herbs and botanical extracts have demonstrated anti-inflammatory, immunomodulatory, and gut-healing properties that make them potential candidates for the management of CD. Here, we provide an updated review on pathogeneses and managements of CD. In particular, we summarize the current understandings of herbal-based treatments for CD and highlights their potential benefits.

Features and Facts of a Gastroretentive Drug Delivery System-A Review.

English oral delivery of drug was the commonly used modality because of patient compliance and ease of administration. After oral administration of any drug, its bioavailability is affected by its residence time in stomach. Recently, gastroretentive drug delivery systems (GRDDS) have gained wide acceptance for drugs with a narrow absorption window, decreased stability at high alkaline pH, and increased solubility at low pH. This approach develops a drug delivery system, which gets retained within gastric fluid, thereby releasing its active principles in the stomach. Some methods used to achieve gastric retention of drugs include the use of effervescence agents, mucoadhesive polymers, magnetic material, bouncy enhancing excipient, and techniques that form plug-like devices that resist gastric emptying. This review provides a concise account of various attributes of recently developed approaches for GRDDS.

3D Printing Technology: A New Milestone in the Development of Pharmaceuticals.

The global market of pharmaceuticals has witnessed a new revolution recently in the form of threedimensional printing (3D) technology. 3D printing has its existence since the 1980s that uses a 3D printer to manufacture the different dosage forms through computer-aided drug design technology. The need for 3D printing is due to numerous advantages like personalized medicine, tailored doses, rapid disintegration in case of SLS technique, incorporation of high doses and taste masking capacity. The different techniques used in 3D printing are Powder based (PB), Semi-solid extrusion (EXT), Fused deposition modeling (FDM), Stereolithographic (SLA) and Selective laser sintering (SLS) 3D printing. However, from the latest reports of association of pharmaceutical 3D printing technology, it is evidenced that this technology is still in its infancy and its potential is yet to be fully explored. The present review includes sections for introduction and scope of 3D printing, personalized medicines and their approaches, historical aspects, research milestones, and various 3D printing techniques.

Recent advances in microneedle composites for biomedical applications: Advanced drug delivery technologies.

In the twenty-first century, microneedles based drug delivery is drawing attention worldwide in the research due to current signs of progress in the controlled release drug delivery through microneedles. The microneedles represent a promising technology to deliver therapeutic compounds into the skin for chronic complications like osteoporosis, diabetes, cancer and induction of immune responses from protein and DNA vaccines. However, the delivery of hydrophilic drugs and macromolecular agents are challenging. In this write up authors included the meticulous illustration of the chronological development of fabrication of microneedles with respect to an assortment of techniques, their modifications, clinical trials and regulatory perspectives period of 2000-2019. This review summarizes characterization, fabrications, biological applications and challenges. Additionally, relevant patents based on microneedle from USPTO) database are also highlighted.

Lipid based nanocarriers: a translational perspective.

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.

Pre-clinical Validation of Mito-targeted Nano-engineered Flavonoids Isolated From Selaginella bryopteris (Sanjeevani) As A Novel Cancer Prevention Strategy.

BACKGROUND: Novel bioactive plant secondary metabolites, including flavonoids, offer a spectrum of chemo-protective responses against a range of human tumor models. However, the clinical translation of these promising anti-cancer agents has been hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. OBJECTIVE: To circumvent the challenges associated with herbal drug development and for effective integration into clinical setting, nano-engineering is one of the emerging pragmatic strategies which has promise to deliver therapeutic concentrations of bio-actives upon oral administration. METHOD: We assessed the nano-encapsulated flavonoid-rich fraction isolated from a traditional Indian herb Selaginella bryopteris (Sanjeevani) (NP.SB). Both in vitro and in vivo studies were performed to evidence the epigenetic protection mechanisms of NP.SB through a mitochondrial-targeted pre-clinical validation strategy. RESULTS: The mito-protective activity of NP.SB revealed a dose-dependent effect when tested in GC-1 spg (mouse spermatogonial epithelial) and B/CMBA.Ov (mouse ovarian epithelial) following exposure to Nsuccinimidyl N-methylcarbamate, a potential human carcinogen. Smaller size, rapid internalization, faster mobility and site specific delivery conferred significant cancer protection in cultured cells. Notably, this encapsulated flavonoid supplementation; prevented emergence of neoplastic daughter clones from senescent mother phenotypes in pro-oxidant treated GC-1 spg and B/CMBA.Ov cells by selective abrogation of mitochondrial oxidative stress-induced aberrant epigenetic modifications. In vivo studies using a diethylnitrosamine and 2- acetylaminofluorene mouse model demonstrated that NP.SB has a significant inhibitory effect on tumor growth which clearly substantiated our in vitro findings. CONCLUSION: Anti-carcinogenic property in conjunction with low toxicity of NP.SB, underscores the translational significance of dietary flavonoids as cancer-protective agents for preferential application in clinical settings.

Carbon Nanotubes: Classification, Method of Preparation and Pharmaceutical Application.

Nanoscience and nanotechnology are emerging areas in the pharmaceutical sciences and the need of modernizing world. Nanoscience is the world of atoms, macromolecular assemblies, macromolecules, quantum dots, and molecules. Nanoscience is the study, and understanding control of phenomena and manipulation of material at the nanoscale. Carbon nanotubes are a tube like material mainly made up of carbon. Only carbon nanotubes are the macromolecules of graphite consisting of sheets of carbon, which is weaved into the cylinder. Graphite sheets look like a hexagonal in shape Nano carbon tubes are about 2 millimetres long and these are one hundred times as stiff as steel. The arrangement of atom in a carbon nanotube is in a form of hexagonal as like as graphite. Carrying capacity of carbon nanotube is 1000 times higher than that of copper thermal stability of it is 4000k, it can be semiconducting or metallic, depending on their diameter and chirality of the atom. These carbon nanotubes having various classifications like single walled CNT's, Multiwalled CNT's, Nano horns, Nano buds, polymerized single walled nanotubes. The review is more focused towards the methods of preparation of nanotubes and their general various applications in pharmacy and medicine along with toxicity. These carbon Nano tubes can be prepared by using various methods with successful ease or application in pharmaceuticals, i.e. gas storage, adsorption, catalyst supported, delivery of drug through targeted system, electrochemistry, bio sensing, fuel cell, photodynamic cells, etc. CNT's are advanced technology in the era of nanotechnology in pharmaceutical sciences which are more emphasizing on patient's compliance and safety. Possessing a broad area of application along with targeted drug delivery. The Scientists are still exploring the various applications of it.

Comparative assessment of lipid based nano-carrier systems for dendritic cell based targeting of tumor re-initiating cells in gynecological cancers.

We aimed to identify an optimum nano-carrier system to deliver tumor antigen to dendritic cells (DCs) for efficient targeting of tumor reinitiating cells (TRICs) in gynecological malignancies. Different lipid based nano-carrier systems i.e. liposomes, ethosomes and solid lipid nanoparticles (SLNPs) were examined for their ability to activate DCs in allogeneic settings. Out of these three, the most optimized formulation was subjected for cationic and mannosylated surface modification and pulsed with DCs for specific targeting of tumor cells. In both allogeneic and autologous trials, SLNPs showed a strong ability to activate DCs and orchestrate specific immune responses for targeting TRICs in gynecological malignancies. Our findings suggest that the mannosylated form of SLNPs is a suitable molecular vector for DC based therapeutics. DCs pulsed with mannosylated SLNPs may be utilized as adjuvant therapy for specific removal of TRICs to benefit patients from tumor recurrence.

Cancer chemopreventive effects of the flavonoid-rich fraction isolated from papaya seeds.

Intervention to decelerate, arrest, or reverse the process of carcinogenesis by the use of either natural or synthetic agents individually or in combination has emerged as a promising and pragmatic medical approach to reduce cancer risk. In the present study, we examined the cancer chemopreventive potential of a flavonoid-rich fraction isolated from the seeds of Carica papaya, a plant traditionally referred to as papaw. The flavonoid-enriched benzene fraction of the aqueous extract exerted its anticancer properties in vitro through cytoprotection, antioxidative and antiinflammatory mechanisms and genoprotection in response to isocyanate-induced carcinogenicity. Medium-term anticarcinogenicity and 2-stage skin papillomagenesis studies conducted in benzopyrene-induced lung carcinogenesis and 7,12-dimethyl benz(a)anthracene-mediated skin papillomagenesis mouse models further validated our in vitro observations. This is the first demonstration of chemopreventive activities of papaya seed products, however, further studies to understand the subtle targets of intracellular signaling pathways, pharmacological profile and toxicological safety of this bioactive fraction are essential to pave the way for successful clinical translation. Our study supports the inverse association between dietary flavonoid intake and cancer risk.

Iontophoresis: a potential emergence of a transdermal drug delivery system.

The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application.

Carbohydrate-conjugated multiwalled carbon nanotubes: development and characterization.

This work presents a novel cascade of chemical functionalization of multiwalled carbon nanotubes (MWCNTs) through chemical modification by a carbohydrate, D-galactose. Galactose-conjugated or galactosylated MWCNTs were synthesized involving the sequential steps of carboxylation, acylation, amine modification, and finally, galactose conjugation. The modification of MWCNTs with galactose was investigated by elemental analysis, x-ray diffraction analysis, Fourier transform-infrared spectroscopy, Raman spectroscopy, and zeta potential measurements, at every sequential step of functionalization. Size and surface characteristics of chemically modified MWCNTs were monitored by transmission electron microscopy and scanning electron microscopy. That galactosylation improved the dispersibility of MWCNTs in aqueous solvents was confirmed by investigation of their dispersion characteristics at different pH values. Thus, the galactosylated MWCNTs as developed could be used for delivery of different bioactive(s) as well as active ligand (galactose)-based targeting to hepatic tissue. FROM THE CLINICAL EDITOR: This work presents a novel cascade of functionalization of multiwalled carbon nanotubes (MWCNTs) through chemical modification by a carbohydrate. Galactosylation improves the dispersibility of MWCNTs in aqueous solvents. The galactosylated MWCNTs could be used for delivery of different bioactive(s) as well as active ligand-based targeting to hepatic tissue.