Nanodiamond Mediated Molecular Targeting in Pancreatic Ductal Adenocarcinoma: Disrupting the Tumor-stromal Cross-talk, Next Hope on the Horizon?

Pancreatic ductal adenocarcinoma (PDAC) is one of the foremost causes of cancer-related morbidities worldwide. Novel nanotechnology-backed drug delivery stratagems, including molecular targeting of the chemotherapeutic payload, have been considered. However, no quantum leap in the gross survival rate of patients with PDAC has been realized. One of the predominant causes behind this is tumor desmoplasia, a dense and heterogenous stromal extracellular matrix of the tumor, aptly termed tumor microenvironment (TME). It plays a pivotal role in the tumor pathogenesis of PDAC as it occupies most of the tumor mass, making PDAC one of the most stromal-rich cancers. The complex crosstalk between the tumor and dynamic components of the TME impacts tumor progression and poses a potential barrier to drug delivery. Understanding and deciphering the complex cascade of tumorstromal interactions are the need of the hour so that we can develop neoteric nano-carriers to disrupt the stroma and target the tumor. Nanodiamonds (NDs), due to their unique surface characteristics, have emerged as a promising nano delivery system in various pre-clinical cancer models and have the potential to deliver the chemotherapeutic payload by moving beyond the dynamic tumor-stromal barrier. It can be the next revolution in nanoparticle-mediated pancreatic cancer targeting.

Targeted Nanotherapies for the Posterior Segment of the Eye: An Integrative Review on Recent Advancements and Challenges.

The eye is a one-of-a-kind sensory organ with intricate anatomy and physiology. It is protected by a variety of barriers, ranging from static barriers to dynamic barriers. Although these barriers are very effective at protecting the eye from exogenous substances and external stress, they are highly compromised by various vision-impairing diseases of both the anterior and the posterior segment of the eye. Due to ocular elimination systems and intricate obstacles that selectively limit drug entry into the eye, effective drug delivery to the posterior segment of the eye (PSE) continues to be a challenge in ophthalmology. Since more than half of the most debilitating eye illnesses are thought to originate in the posterior segment (PS), understanding the physiology and clearance mechanism of the eye could help design improved formulations that could be noninvasive and intended for targeted posterior segment therapeutics. Moreover, the major drawback associated with the conventional drug delivery system to PSE is minimal therapeutic drug concentration in the desired ocular tissue and life-threatening ophthalmic complications. One possible approach that can be implemented to overcome these ocular barriers for efficient ocular therapy, non-invasive and targeted drug action to the posterior tissues is by designing nanomedicines. This review summarizes the recent non-invasive and patient compliant advances in designing nanomedicines targeting PSE. The various routes and pathways of drug administration to the ocular tissue are also summarized.

Evaluation of a novel melatonin-loaded gelatin sponge as a wound dressing.

BACKGROUND: For Melatonin, the pineal gland hormone, also known as the neuroendocrine hormone, influences angiogenesis by exerting a positive effect on fibroblast, monocyte, and cytokine proliferation. Formulation and study of characteristics of gelation-based Melatonin sponge crosslinked with fructose using the surfactant foaming and freeze-drying method for wound healing application was the objective of our study. The structure of the formulated gelatin sponge was observed using a scanning electron microscope and showed to have abundant and uniform pores. Characteristics were studied using digestibility test, water uptake test, porosity measurement test, moisture uptake test, tensile strength test, folding endurance test, scanning electron microscopy, Fourier transform infrared spectroscopy, and drug entrapment efficiency analysis. RESULTS: The obtained data showed that the formulated sponge had good mechanical properties, water uptake, and water retention capacities. In animal experiments, histological and macroscopic observations showed that wounds covered by gelatin loaded with a Melatonin sponge healed quickly. CONCLUSION: The formulated sponge was a potential wound healing material having suitable physical, mechanical properties and biocompatibility. The graphical abstract is shown in Figure 1.

Grape seed extract: having a potential health benefits.

Grapes are one of the most highly consumed fruits across the world. In ancient Europe the leaves and the sap of grape plants has been used in traditional treatment for ages. Besides being a wellspring for vitamins and fibre, the skin and seeds of grapes are highly rich in Polyphenols specifically proanthocyanidins, which can be used as a functional ingredient to address various health issues by boosting the natural bio-processes of the body. Since, grape seeds are by product of wine making companies therefore can be easily procured. The present review article briefly describes the various pharmacological activities of grape seed extract and different experimental studies were done which supports the beneficial health qualities of the extract. Through different and various studies, it was proved that the proanthocyanidin rich grape seed extract provides benefits against many diseases i.e. inflammation, cardiovascular disease, hypertension, diabetes, cancer, peptic ulcer, microbial infections, etc. Therefore, beside from using it as a nutraceutical or cosmeceutical, as a result they may have a potential to substitute or complement in currently used drugs in the treatment of diseases by developing it into other successful pharmaceutical formulations for better future prospective.

Erlotinib-loaded carboxymethyl temarind gum semi-interpenetrating nanocomposites.

Erlotinib-loaded carboxymethyl temarind gum-g-poly(N-isopropylacrylamide)-montmorillonite based semi-IPN nanocomposites were synthesized and characterized for their in vitro performances for lung cancer therapy. The placebo matrices exhibited outstanding biodegradability and pH-dependent swelling profiles. The molar mass (M¯ c) between the crosslinks of these composites was declined with temperature. The solid state characterization confirmed the semi-IPN architecture of these scaffolds. The corresponding drug-loaded formulations displayed excellent drug-trapping capacity (DEE, 86-97 %) with acceptable zeta potential (-16 to -13 mV) and diameter (967-646 nm). These formulations conferred sustained drug elution profiles (Q8h, 77-99 %) with an initial burst release. The drug release profile of the optimized formulation (F-3) was best fitted in the first order kinetic model with Fickian diffusion driven mechanism. The mucin adsorption to F-3 followed Langmuir isotherms. The results of MTT assay, AO/EB staining and confocal analyses revealed that the ERL-loaded formulation suppressed A549 cell proliferation and induced apoptosis more effectively than pristine drug.

Novel drug delivery systems for ocular therapy: With special reference to liposomal ocular delivery.

Delivery of drugs to eyes is a great challenge to researchers because of a number of barriers in the eye preventing the actual dose from reaching the site. A number of ophthalmic delivery systems have been developed in the past couple of years that are not only new but also safe and reliable and help to overcome all those barriers in the eye which are responsible for the very less bioavailability of drugs. In this review, we tried to focus on current research in ocular delivery of drug substances giving special emphasis to liposomal delivery system. A brief analysis of other novel ocular delivery systems, ocular physiology, and microbial sources of disease are also highlighted herein. We analyzed the various research findings for churning a general idea for novel ocular delivery system and its future use. The novel formulations may overcome the addressed problems of ophthalmic medication and comply with the quality assurance issues. The liposomal delivery is advantageous as they have the ability to entrap both hydrophobic and hydrophilic drugs and are suitable for delivery to both the anterior and posterior segment of the eye. Therefore, the use of this alternative approach is quite a necessity.