Jobin Jose

RNA Interference Using c-Myc–Conjugated Nanoparticles Suppresses Breast and Colorectal Cancer Models

In this article, we report the development and preclinical validation of combinatorial therapy for treatment of cancers using RNA interference (RNAi). RNAi technology is an attractive approach to silence genes responsible for disease onset and progression. Currently, the critical challenge facing the clinical success of RNAi technology is in the difficulty of delivery of RNAi inducers, due to low transfection efficiency, difficulties of integration into host DNA and unstable expression. Using the macromolecule polyglycidal methacrylate (PGMA) as a platform to graft multiple polyethyleneimine (PEI) chains, we demonstrate effective delivery of small oligos (anti-miRs and mimics) and larger DNAs (encoding shRNAs) in a wide variety of cancer cell lines by successful silencing/activation of their respective target genes. Furthermore, the effectiveness of this therapy was validated for in vivo tumor suppression using two transgenic mouse models; first, tumor growth arrest and increased animal survival was seen in mice bearing Brca2/p53-mutant mammary tumors following daily intratumoral treatment with nanoparticles conjugated to c-Myc shRNA. Second, oral delivery of the conjugate to an Apc-deficient crypt progenitor colon cancer model increased animal survival and returned intestinal tissue to a non–wnt-deregulated state. This study demonstrates, through careful design of nonviral nanoparticles and appropriate selection of therapeutic gene targets, that RNAi technology can be made an affordable and amenable therapy for cancer. Mol Cancer Ther; 14(5); 1259–69. ©2015 AACR.

Prolonged drug delivery system of an antifungal drug by association with polyamidoamine dendrimers

Introduction: The potent antifungal agent amphotericin B (AmB) is not freely soluble in water. The clinical use of AmB is limited by nephrotoxicity and poor water solubility. Polyamidoamine (PAMAM) dendrimer offers an identical carrier for drug binding that has the capacity to attach and discharge drugs in numerous ways. Materials and methods: In this research work, we explored the potential of PAMAM dendrimers to improve the solubility of AmB. Results and discussion: The experimental results indicated that the solubility of AmB was greatly enhanced in the presence of PAMAM dendrimer solutions. Results indicated that the solubility of AmB enhanced with increase in dendrimer generations as well as concentration. In vitro release studies of AmB in the presence of the third generation of PAMAM dendrimers was performed by the dialysis method. Our research work revealed that binding of drug into dendrimers led to sustained release of AmB in vitro. Conclusion: Based on the stability studies, it was concluded that the drug dendrimer complex should be stored in a dark place at a cool temperature.

Methods for Testing Ocular Toxicity: Current Status

The developed ophthalmic formulations should be tested for ocular toxicity testing like draize eye test. Rapid growth in the field of ocular toxicity testing replaces the usage of animals and to adopt the modified protocols. The researchers have to develop properly validated and regulatory approved options to animal testing. Alternative ocular toxicity testing is based on corneal structure and mechanism through which the specific ocular formulation causes irritation to the eyes. Several alternative assay methods have been introduced in the field of ocular toxicity testing like in vitro organotypic model for testing ocular toxicity and several other methods like Bovine Corneal Opacity and Permeability Assay (BCOP Assay), isolated chicken eye test, isolated rabbit eye test and Hens egg-test on the chorioallantoic membrane. The ultimate aim of alternate methods of ocular toxicity testing is to develop properly validated and regulatory approved best practices. Hence this review highlights the development in the field of alternative ocular toxicity testing methods.

Organogels: A Versatile Drug Delivery Tool in Pharmaceuticals

Organogels have been explored as a versatile tool in pharmaceuticals for topical as well as transdermal delivery of various drugs. These are semisolid systems consists of apolar phase and a solid phase. Gels are formed by the mechanism of entrapment of a polar phase into the three-dimensional networked structure of solid phase. Apolar phase is used as a solvent such as isopropyl palmitate, isopropyl myristate etc. Solid phase is an organogelator such as sorbiatan monostearte, lecithin etc. These systems are good carrier for both hydrophilic and lipophilic therapeutic agents. The present review describes some of the important properties of organogel, different types of organogel based on organogelator, method of preparation and various applications in pharmaceuticals.

Novel ethosomal gel of clove oil for the treatment of cutaneous candidiasis

Dual‐release mechanism of ethosomal gels (ie, ethosomes and gel) makes them as versatile drug delivery systems for topical applications. Clove oil is obtained from the clove buds exhibited broad antifungal and antibacterial activity. Cutaneous candidiasis is the infection caused by Candida albicans or other Candida species.

Formulation and Evaluation of Antibacterial Herbal gels of Murraya koenigii Leaves Extract

Herbal medicine has become an item of global importance both medicinal and economical. Herbal remedies are getting increasing patient compliance as they are devoid of typical side effects of allopathic medicines. The present research has been undertaken with the aim to formulate and evaluate the herbal gels containing Murraya koenigii (curry leaves) plant leaf extract. The gel formulations were prepared by using Carbapol 940, Murraya koenigii leaf extract, propylene glycol, methyl paraben, propyl paraben, glycerine and required amount of distilled water. The skin pH (6.8-7) was maintained by drop wise addition of Tri-ethanolamine. The physical parameters of formulated gels like colour, homogeneity, pH, viscosity and spreadibility were evaluated. The gels were evaluated for antibacterial efficiency by agar diffusion method against some bacterial agents. The herbal gels showed that formulations containing Murraya koenigii leaves extract have better antibacterial activity.

Formulation and Evaluation Ungual Drug Delivery System of Antifungal Agent for Nail Disorders

Fungal infections affecting nails are commonly seen around the world. The effectiveness of topical therapies is limited by minimal drug permeability through the nail plate. Nail permeability is however quite low and limits topical therapy to early/mild disease states such as onychomycosis (fungal infections of the nail). The current research aims at ungual drug delivery system as an effective treatment in nail infections. The formulations of nail lacquer were made with Amorolfine as antifungal agent using different concentration of polymer Eudragit RL 100 (ERL 100). Among 6 formulations, formulation F5 and F6 showed very good physical characteristics like viscosity, water resistance, stability, drying time, smoothness as compared to other formulations. The zone of inhibition of antifungal activity showed desired results (F5 and F6).

In Vitro Cytotoxicity Studies of Pamam Dendrimer with an Antifungal Agent

PAMAM dendrimer offers an ideal carrier for drug delivery that has the capacity to attach and discharge drugs by numerous ways. In this research work, we explored the potential of polyamidoamine dendrimers (PAMAM) as a carrier for ketoconazole and in vitro evaluation of ketoconazole-PAMAM complexes. Cytotoxicity studies were carried in J774A, mouse macrophage cell lines. Our research work revealed that binding of drug into dendrimers led to sustained release of ketoconazole in vitro. Results of the cytotoxicity studies also showed that the complexation of drugs with PAMAM dendrimer leads to the reduction in cytotoxicity of drugs.

Formulation and Evaluation of Rizatriptan Matrix Tablet

Mucoadhesive polymer owing to its binding capacity with gastric mucin prolongs the gastric residence time and thereby increases bioavailability. In the present research work an attempt was made to formulate and evaluate sustain release mucoadhesive matrix tablet of Rizatriptan. Matrix tablets were prepared by direct compression technology using different types and levels of polymers viz. HPMC K15M, carbopol 934P, ethyl cellulose etc alone and in combinations. Compressed tablets were evaluated for thickness, friability, hardness, uniformity of weight, content of active ingredient, swelling and in vitro dissolution studies. The studies indicated that the drug release can be modulated by varying the concentrations of polymers. It was observed that combination of both the polymers in equal concentration exhibited the best release profile and able to sustain the drug release for 10h. Kinetic studies were also carried out on different formulations which showed that formulation RF1, RF2, RF3, RF7, RF8 and RF10 followed zero order while RF4, RF5, RF6 and RF10 followed first order release kinetics. According to Korsmeyer Peppas, RF1, RF2,RF3, RF7,RF8,R F9 and R F10 showed non fickian diffusion. While RF4, RF5 and R F6 followed fickian diffusion. Stability studies revealed that all the formulation was found to be stable under accelerated stability studies.