We report asialoglycoprotein receptor (ASGPR)-targeted doxorubicin hydrochloride (Dox) nanoparticles (NPs) for hepatocellular carcinoma (HCC). Polyethylene sebacate (PES)-Gantrez® AN 119 Dox NPs of average size 220 nm with PDI < 0.62 and ∼20% Dox loading were prepared by modified nanoprecipitation. ASGPR ligands, pullulan (Pul), arabinogalactan (AGn), and the combination (Pul-AGn), were anchored by adsorption. Ligand anchoring enabled high liver uptake with a remarkable hepatocyte:nonparenchymal cell ratio of 85:15. Furthermore, Pul-AGn NPs exhibited an additive effect implying incredibly high hepatocyte accumulation. Galactose-mediated competitive inhibition confirmed ASGPR-mediated uptake of ligand-anchored NPs in HepG2 cell lines. Subacute toxicity in rats confirmed the safety of the NP groups. However, histopathological evaluation suggested mild renal toxicity of AGn. Pul NPs revealed sustained reduction in tumor volume in PLC/PRF/5 liver tumor-bearing Nod/Scid mice up to 46 days. Extensive tumor necrosis, reduced collagen content, reduction in the HCC biomarker serum α-fetoprotein (p < 0.05), a mitotic index of 1.135 (day 46), and tumor treated/tumor control (T/C) values of <0.42 signified superior efficacy of Pul NPs. Furthermore, weight gain in the NP groups, and no histopathological alterations indicated that they were well tolerated by the mice. The high efficacy coupled with greater safety portrayed Pul Dox NPs as a promising nanocarrier for improved therapy of HCC.

Nucleic acids show immense potential to treat cancer, acquired immune deficiency syndrome, neurological diseases and other incurable human diseases. Upon systemic administration, they encounter a series of barriers and hence barely reach the site of action, the cell. Intracellular delivery of nucleic acids is facilitated by nanovectors, both viral and non-viral. A major advantage of non-viral vectors over viral vectors is safety. Nanovectors evaluated specifically for nucleic acid delivery include polyplexes, lipoplexes and other cationic carrier-based vectors. However, more recently there is an increased interest in inorganic nanovectors for nucleic acid delivery. Nevertheless, there is no comprehensive review on the subject. The present review would cover in detail specific properties and types of inorganic nanovectors, their preparation techniques and various biomedical applications as therapeutics, diagnostics and theranostics. Future prospects are also suggested.

The present study reports the comparative pharmacokinetic evaluation and biodistribution of rifampicin (RIF) following oral administration of nanoparticles of a bioadhesive polymer, Gantrez and a hydrophobic polymer poly(ethylene sebacate) (PES). A specific objective of the study was to evaluate lung uptake of the nanoparticles following oral administration. Nanoparticles were obtained in the size range 350-450 nm with rifampicin loading of 12-14% w/w. Zeta potential confirmed colloidal stability. PES nanoparticles revealed high macrophage uptake compared to Gantrez nanoparticles, and direct correlation was observed between hydrophobicity (contact angle) and macrophage uptake (r2 -0.940). Enhanced RIF uptake with folic acid anchoring suggested folate receptor mediated uptake. RIF nanoparticles exhibited significantly higher Cmax and AUC, delayed Tmax and sustained release compared to plain RIF. More importantly the plasma concentration of RIF with the nanoparticles was significantly greater than the MIC of RIF (0.25 microng/mL) over 24 h. While gamma scintigraphy revealed higher lung accumulation of nanoparticles, the concentration with Gantrez nanoparticles was significantly higher. HPLC evaluation of lung concentration correlated with scintigraphy data. The significantly higher bioavailability and lung accumulation with Gantrez nanoparticle over PES nanoparticles was attributed mucoadhesion and high affinity of Gantrez to the Peyer's patches. Our study suggests Gantrez nanoparticles as a promising carrier for enhancing lung accumulation of drugs.

We report carbohydrate-anchored polyethylene sebacate (PES)-Gantrez Õ AN 119 Doxorubicin hydrochloride (Dox) nanoparticles (NPs) for enhanced anticancer efficacy. The carbohydrates Arabinogalactan (AGn), an adjuvant in anticancer chemotherapy and pullulan (Pul) reported to promote collagen synthesis, were selected as ligands. PES Dox NPs of an average size around 200 nm, greater than 20% w/w Dox loading and negative zeta potential were anchored with Pul, AGn, and Pul-AGn combination by simple incubation. Increase in particle size and zeta potential confirmed carbohydrate anchoring. FTIR confirmed ionic complexation of Dox and Gantrez Õ AN 119. DSC and XRD demonstrated amorphization of Dox. Higher Dox release in pH 5.5 as compared with pH 7.4 is beneficial for reduced systemic toxicity and enhanced drug release in tumors. Good in vitro serum stability and low hemolysis revealed suitability for intravenous administration. All NPs revealed circulation longevity in normal rats. Pul NPs revealed superior anticancer efficacy in vitro and an 11-fold enhancement in uptake in MCF-7 breast cancer cells. The greater efficacy in vivo is attributed to possible pullulan-mediated integrin receptor uptake and interaction with tumor collagen. Histopathology confirmed safety and suggested promise of Pul NPs in improved anticancer efficacy.