Advancements in phytochemistry have led to the development of phytochemicals as promising agents for cancer treatment and prevention [1]. Polydatin (piceid 3,5,41-trihydroxystilbene-3-O-β-d-glucopyranoside), is a natural potent stilbenoid polyphenol. Once absorbed, polydatin gets converted to resveratrol, a well know phytochemical with significant effects in many diseases including cancer [2]. Polydatin is the most abundant glycoside form of resveratrol in nature. It is present in 10 times higher amounts, possess distinct protein interactions, and has better retention time inside human cells by virtue of its glycosylation. The core stilbene structure of polydatin is similar to resveratrol and many of their biological effects overlap significantly. Polydatin possses better biological activities such as antioxidant, anti-inflammatory, and anticancer than resveratrol by modulating various signal transduction pathways in many tumor cells [3]. Due to glycosylated moiety polydatin is a potential therapeutic agent with fewer pharmacokinetic limitations as compared to resveratrol. It has higher water solubility (1700 fold), yet it is not directly absorbed by the intestinal cells and requires active sodium dependent glucose transporter 1 [SGLT 1]. Therefore despite several advantages over resveratrol the therapeutic potential of polydatin is limited by its poor absorption and low bioavailability [4].

Several studies have reported earlier the use of various nanocarriers for increasing the solubility and bioavailability of polydatin such as polymers, lipid carriers, micelles, nanofibres etc [2]. However, overall required therapeutic index has not been achieved so far due to aggregation, non-specific immune response, limited entrapment efficiency and size regulation [[5], [6], [7]].

Recently biopolymeric nanoparticles have revolutionalized the scientific field with several advantages as drug carriers due to increased bioavailability, small size, controlled release, high encapsulation efficiency, and enhanced permeation and retention (EPR) effect. Their multi-functionality such as site-specific drug delivery, drug stabilization and potential for surface functionalization are important advantages [8].

In the present study we have designed & synthesize biopolymeric nanoformuations, one without polydatin [ (PG-B NPs i.e Blank) containing Polycaprolactone (PCL) and Gelatin] and the other in which polydatin is also added [(PPG-NPs) Polydatin loaded gelatin coated Polycaprolactone biopolymeric nanoparticles]. Nanoparticles were prepared by nanoprecipitation method using three main components, the polymer [PCL], the Acetone [organic solvent for PCL] and the water [9].

PCL is biocompatible, biodegradable, hydrophobic, semi crystalline FDA approved polymer used for sustained release of drugs at physiological pH [10]. It is exceptionally cheap biomaterial when compared with other biodegradable polymers (PLGA) and it has a slow degradation rate. It is a cost-effective polymer and does not create an acidic environment during its degradation. It has desirable mechanical properties and is non-immunogenic too [11]. However due to hydrophobic nature PCL has poor wettability and poor cell attachment. To overcome these limitations ‘Gelatin Type A’ was coated onto the PCL to increase the hydrophilicity of nanoparticles. Gelatin is biocompatible and biodegradable. It is non-toxic and is degraded through protease enzymatic hydrolysis into its individual amino acid components [12]. Both polymer [PCL] and our phytochemical [polydatin] are hydrophobic in nature so Pluronic F127 was added to act as a sacrificial biolink and to provide extra stability. Pluronic F127 is a FDA approved commonly used biosurfactant to inhibit drug efflux transport [13]. The bioefficacy of nanoparticles was studied in A549 lung cancer cell lines and A549 radioresistant cell lines in-vitro both on 2D and 3D spheroids cultures. Polydatin is one of the versatile phytochemicals which can have radio sensitising effect in cancer cells and at the same time can protect against the side effects of radiation therapy. It has been reported to exhibit minimal toxicity to non-tumorigenic cells suggesting a favourable therapeutic profile [[14], [15], [16]].