Nanoparticles in pancreatic cancer therapy: a detailed and elaborated review on patent literature.

INTRODUCTION: Nanotechnology may open up new avenues for overcoming the challenges of pancreatic cancer therapy as a broad arsenal of anticancer medicines fail to realize their full therapeutic potential in pancreatic ductal adenocarcinoma due to the formation of multiple resistance mechanisms inside the tumor. Many studies have reported the successful use of various nano formulations in pancreatic cancer therapy. AREAS COVERED: This review covers all the major nanotechnology-based patent litrature available on renowned patent data bases like Patentscope and Espacenet, through the time period of 2007-2022. This is an entirely patent centric review, and it includes both clinical and non-clinical data available on nanotechnology-based therapeutics and diagnostic tools for pancreatic cancer. EXPERT OPINION: For the sake of understanding, the patents are categorized under various formulation-specific heads like metallic/non-metallic nanoparticles, polymeric nanoparticles, liposomes, carbon nanotubes, protein nanoparticles and liposomes. This distinguishes one specific nanoparticle type from another and makes this review a one-of-a-kind comprehensive patent compilation that has not been reported so far in the history of nanotechnological formulations in pancreatic cancer.

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.

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.

Transdermal Lipid Nanocarriers: A Potential Delivery System for Lornoxicam.

BACKGROUND: Lornoxicam, is a NSAID of the oxicam class. Its short duration of action owing to rapid elimination and gastrointestinal side effects limits its usefulness when administered orally. OBJECTIVE: The primary objective of the proposed work is to develop suitable lipid nanocarriers for transdermal delivery of Lornoxicam with increased drug residence time at local site of inflamation and in systemic circulation, overcoming undesired gastrointestinal side effects. METHOD: Lornoxicam loaded lipid nanocarriers like solid lipid nanocarriers (SLN), nano-structured lipid carriers (NLC) & nanoemulsions (NE) were prepared by high-speed homogenization technique. RESULT: The particle size, zeta potential, and polydispersity index as obtained, were in the range of 140- 193 nm, -22 to -32 mV, and 0.354-0.301 for SLN formulations and 146-201 nm, -23 to -30 mV, and 0.355-0.354 for NLC formulations respectively. Characterization of stable NE revealed that globule size, zeta potential and polydispersity index were within the range of 138 to 195 nm, -26.1±0.123 mV and 0.195 ± 1.231 respectively. It was also observed that entrapment efficacy and drug loading improved as the lipid concentration was increased. The results obtained from the in vitro permeation study and in vivo anti-inflammatory study showed controlled drug permeation, increased bioavailability, longer retention and better therapeutic potential of Lornoxicam after transdermal application of lipid nanoparticles as compared to conventional gel. CONCLUSION: It can be concluded that the developed lipid nanoparticle loaded gel was found to be a suitable drug delivery carrier for transdermal delivery of Lornoxicam to increase the residence time of drug in systemic circulation and to combat the gastrointestinal side effects.

Nano lipid-drug conjugate: An integrated review.

Lipid-drug conjugates (LDC), which may also be addressed as lipoidal prodrug, have the therapeutic actives chemically bound to a lipid moiety like fatty acids or phospholipids. Fabricated in nano-size, lipid-drug conjugate forms another breed of lipid nanoparticles. LDCs are prepared in order to increase the drug loading and hence prevent leakage of a highly polar drug from a lipophilic matrix. In turn, it assists to achieve active targeting of therapeutics with reduced side effect by altering the pharmacokinetic profile of the drug. These self-assembled systems take the benefit of metabolic pathways of lipid biochemistry, allowing suitable organ targeting depending upon its size. These lipids because of its similarities with physiological lipids, enhances the solubility of the therapeutic agents and thereby improve the bioavailability. This present review is meant to encompass different aspects related to lipid drug conjugates which include types of lipids and drugs that can be used to develop this type of formulation. Here, we throw light on methods of preparation of lipid drug conjugate, processing them into nanoparticle, its characterization and different applications of lipid drug conjugate. We aim to present a holistic view on lipid drug conjugate as a suitable drug delivery approach.

Topical delivery of paclitaxel for treatment of skin cancer.

CONTEXT: Skin cancer represents the most growing types of cancer in human and ultraviolet radiation can be cited as one of the prime factor for its occurrence. Current therapy of skin cancer suffers from numerous side effects; for effective therapy, topical application of formulation of paclitaxel (PTX) can be considered as a novel approach. OBJECTIVE: The present study is an attempt to prepare formulation of solid lipid nanoparticles (SLN) of PTX for the effective treatment of various form of skin carcinoma. METHODS: The SLN were prepared by high-speed homogenization and ultrasonication method. The prepared SLN were characterized. The optimized PTX SLN were loaded in carbopol gel. The prepared gels were evaluated for its gelling properties and finally studied for in vivo anti-cancer efficacy and histopathological study. RESULTS: The particle size distribution was found to be in the range of 78.82-587.8 nm. The product yield (%) was found between 60% and 66% and showed a highest entrapment efficiency of 68.3%. The in vitro release of the drug from SLN dispersion was found to be biphasic with the initial burst effect, followed by slow release. SLN-loaded gel were subjected to permeability study and the results show steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio were significantly increased in SLN-loaded gel formulation as compared with PTX-loaded gel. The histopathological study clearly reveals the efficacy of the SLN-F3 3G in the treatment of skin cancer. CONCLUSION: The experimental formulations show controlled release of PTX and thus expected to show reduce dose-related side effects.

Design and development of a safer non-invasive transungual drug delivery system for topical treatment of onychomycosis.

OBJECTIVE: The main objective of this study is to develop a safer non-invasive treatment for nail infections since the current treatment regimen has drawbacks like, incidence of systemic side-effects and higher cost. Proposed topical treatment on the other hand can drastically improve the situation, hence highly desirable. This work was undertaken with a hypothesis to develop a transungual microemulsion gel for topical treatment of onychomycosis. METHODS: Benzyl alcohol and isopropyl myristate were used as oil, Pluronic F68 as surfactant and ethanol as co surfactant, in double-distilled water and loading itraconazole as the model antifungal drug. Pseudo-ternary phase diagram was developed by titrating different ratios of total oil and water with total surfactant, and Km ratio was fixed at 1:1. Microemulsion formulations were prepared based on the phase diagram and incorporated in gels by adding Carbopol 934P. Nail permeation enhancers like urea and salicylic acid were used to increase drug permeation through the nail plate. Parameters like drug loading, clarity, particle size distribution, drug entrapment efficiency (DEE), drug release profile, release kinetics and nail uptake were checked for the evaluation of the formulations. RESULTS: Complete release of drug from the formulation varied from 60 to 120 min. The optimized formulation had DEE of 92.75%, complete drug release in 60 min and highest nail uptake of 0.386%/mm(2) (39 µg of drug) with 5% urea as nail permeation enhancer. CONCLUSION: The formulation may prove beneficial in safer treatment of onychomycosis.