RNA interference (RNAi) is a wondrous phenomenon that silences the expression of targeted genes via distinct messenger RNA degradation pathways. It has the potential as a therapeutic agent for variety of diseases, including viral infections, cancer, and immune diseases. RNAi mainly conducts gene regulation by 3 ways: microRNA, short hairpin RNA, and small interfering RNA. However, in vivo delivery of RNAi therapeutics is restricted because of charge density, molecular weight, and instability in the presence of nucleases. Furthermore, intracellular accumulation and endosomal escape have remained significant barriers in the delivery of these macromolecules. Many viral and nonviral delivery vectors have been thoroughly investigated to overcome these barriers. Researchers have found applications for RNAi in a variety of diseases and, hence, various delivery systems have been explored to satisfy the need. Both local and systemic strategies have been utilized to elicit RNAi's effect and each carries its own therapeutic implications with varying margins of safety. This review is an effort to describe the types of RNAi and their application in a variety of diseases using both local and systemic delivery approaches. It is sure that advancement in this direction will evolve a new landscape for treating a range of diseases.

Cationic liposomes have long been used as non-viral vectors for small interfering RNA (siRNA) delivery but are associated with high toxicity, less transfection efficiency, and in vivo instability. In this investigation, we have developed siRNA targeted to RRM1 that is responsible for development of resistance to gemcitabine in cancer cells. Effect of different lipid compositions has been evaluated on formation of stable and less toxic lipoplexes. Optimized cationic lipoplex (D2CH) system was comprised of dioleoyl-trimethylammoniumpropane (DOTAP), dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), hydrogenated soya phosphocholine (HSPC), cholesterol, and methoxy(polyethyleneglycol)2000-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG2000-DSPE). D2CH lipoplexes have shown particle size (147.5 ± 2.89 nm) and zeta potential (12.26 ± 0.54 mV) characteristics essential for their in vivo use. In vitro cytotoxicity study has shown low toxicity of developed lipoplexes as compared with lipofectamine-2000 up to N/P ratio as high as 7.5. Cell uptake studies and gene expression studies have confirmed intracellular availability of siRNA. In addition, developed lipoplexes also showed ~3 times less hemolytic potential as compared with DOTAP/DOPE lipoplexes at lipid concentration of 5 mg/mL. Lipoplexes also maintained particle size less than 200 nm on exposure to high electrolyte concentration and showed >70% siRNA retention in presence of serum showing siRNA protection conferred by lipoplexes. Furthermore, in vivo acute toxicity studies in mice showed that formulation was non-toxic up to a dosage of 0.75 mg of siRNA/kg as lipoplexes and 300 mg lipid/kg as blank liposomes indicating tolerability of lipoplexes at a dose much higher than required for therapeutic use. Promising results of this study warrant further investigation of developed siRNA lipoplexes for cancer treatment.

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This study was aimed to develop and evaluate p53 polyplex-loaded enteric-coated calcium pectinate microbeads for oral gene delivery as an effective novel alternative for colorectal cancer therapy. Mutation in p53 is the key event in colorectal cancer (CRC) and an important target for the treatment of CRC through gene therapy. Polymethacrylates-based non-viral vectors were evaluated for their ability to complex, protect and transfect p53 (wt) into colon cancer cell line. Polyplexes were formulated by complexation of cationic polymer with anionic pDNA at different N/P ratios. p53 polyplex-loaded calcium pectinate (CP) microbeads were prepared by ionotropic gelation of pectin with calcium chloride and coated with Eudragit Õ S100. In vitro release studies showed that enteric-coated CP microbeads protected the release of p53 polyplex in upper GIT with less than 10% release. In-vitro cell line studies and in vivo studies in rat showed that polymethacrylate carrier could transfect the pDNA effectively. Results of in vivo gene expression study further confirmed the ability of enteric-coated calcium pectinate microbeads to deliver pDNA specifically to rat colon. Conclusively, enteric-coated calcium pectinate microbeads released p53 polyplex specifically in colon and could serve as an effective alternative for CRC therapy.

Abstract. Cisplatin, first (platinum) compound to be evolved as an anticancer agent, has found its important place in cancer chemotherapy. However, the dose-dependent toxicities of cisplatin, namely nephrotoxicity, ototoxicity, peripheral neuropathy, and gastrointestinal toxicity hinder its widespread use. Liposomes can reduce the toxicity of cisplatin and provide a better therapeutic action, but the low lipid solubility of cisplatin hinders its high entrapment in such lipid carrier. In the present investigation, positively charged reactive aquated species of cisplatin were complexed with negatively charged caprylate ligands, resulting in enhanced interaction of cisplatin with lipid bilayer of liposomes and increase in its encapsulation in liposomal carrier. Prepared cisplatin liposomes were found to have a vesicular size of 107.9±6.2 nm and zeta potential of −3.99±3.45 mV. The optimized liposomal formulation had an encapsulation efficiency of 96.03±1.24% with unprecedented drug loading (0.21 mg cisplatin/mg of lipids). The in vitro release studies exhibited a pH-dependent release of cisplatin from liposomes with highest release (67.55 ± 3.65%) at pH 5.5 indicating that a maximum release would occur inside cancer cells at endolysosomal pH. The prepared liposomes were found to be stable in the serum and showed a low hemolytic potential. In vitro cytotoxicity of cisplatin liposomes on A549 lung cancer cell line was comparable to that of cisplatin solution. The developed formulation also had a significantly higher median lethal dose (LD 50 ) of 23.79 mg/kg than that of the cisplatin solution (12 mg/kg). A promising liposomal formulation of cisplatin has been proposed that can overcome the disadvantages associated with conventional cisplatin therapy and provide a higher safety profile.

Background: Epirubicin-HCl is highly efficient for breast cancer management at a concentration of 60-90 mg/m

These results suggest the application of present siRNA delivery strategy to potentiate the chemotherapeutic effect by means of chemosensitization which may be utilized for effective and thorough remission of lung cancer.

Lung cancer occurrence throughout the world and its unsatisfactory treatment has drawn significant attention from many medical agencies. A genomic approach utilizing siRNA against target gene may resolve this problem. Present investigation includes siRNA lipoplex formulation and its in-vitro characterisation in lung cancer cell line for intracellular uptake and cytotoxicity. Accumulation of siRNA inside the cell as well as less cytotoxicity of prepared carrier system signifies potential of prepared siRNA lipoplex in the treatment of lung cancer.