Pharmaceutical Nanotechnology (v.2, #3)

Editorial: by Ijeoma Uchegbu (115-115).

Frontier Lipid-Based Carrier Systems for Drug Targeting: A Laconic Review on Niosomes by Rajendra Awasthi, Sumit Kumar, Giriraj T. Kulkarni (116-128).
Since, the first report on cosmetic applications of non-ionic surfactant vesicles by L'Oreal, numerous papers have been published reporting success of niosomes in drug delivery. Niosomes are considered as one of the most successful drug carrier system applying nanotechnology to potentiate the therapeutic efficacy and reduce toxicities of conventional therapies. Niosomes are biodegradable, nontoxic and nonionic surfactants based vesicular drug carriers. The recent advancements in the pharmaceutical research are focused on the development of new delivery systems based on micro or nano-sized carriers to modulate the drug delivery, targeting as well as to improve the drug stability. Niosome are effective drug carrier with the ability of encapsulating both lipophilic and hydrophilic drugs. This laconic review exhaustively focuses on the potential of niosomal drug delivery with special emphasis on their role in drug targeting, advantages and disadvantages, formulation approaches and applications of niosomes in the disease therapy.

Size-tuneable Nanometric MRI Contrast Agents for the Imaging of Molecular Weight Dependent Transport Processes by Mazen M. El-Hammadi, Steven MacLellan, Christine Dufes, William M. Holmes, Barrie Condon, Ijeoma F. Uchegbu, Andreas G. Schatzlein (129-137).
The purpose of the current study was to evaluate size-tuneable polymeric glycol-chitosan (GC)-DTPAGadolinium (Gd) conjugates as MRI contrast agents that can be used as a platform for imaging of molecular weight (MW) dependent transport processes. GC-DTPA-Gd conjugates of precisely controlled MWs were synthesised and evaluated in mice against Gd-DTPA using time series of high-resolution MRI images of trunk, head, and xenograft flank tumours. GC-DTPA modification ratio was one DTPA per 3.9-5.13 of GC monomers. GC-DTAP-Gd provided overall superior contrast compared to Gd-DTPA with the duration of the enhancement depending on MW (?1hr for 40kD). The kidneys showed early enhancement also, particularly in the renal pelvis, suggesting renal elimination. Imaging of the head with GC-DTPA-Gd allowed detailed anatomical identification of specific blood vessels in particular with the high MW CA agent. Sequential, high-resolution, isotropic imaging of established A431 xenograft flank tumours with DTPA-Gd and GC-DTPA-Gd demonstrated that the initial distribution of the contrast agents was well correlated with blood vessels and supply. In contrast, subsequent tissue transport was primarily by diffusion and limited by CA molecular weight. The data also highlight the role of heterogeneity in CA distribution which was more prominent for the high MW agent. Precise control of glycol chitosan (GC) polymer chemistry facilitates synthesis of a family of Gd-based MRI contrast agents of tuneable MW but otherwise identical physicochemical properties. Such agents allow isotropic high-resolution threedimensional imaging of MW dependent transport processes relevant to the clinical and pre-clinical prediction of drug transport processes.

ICH Q8 Guidelines in Practice: Spray Drying Process Optimization by 23 Factorial Design for the Production of Famotidine Nanoparticles by Anita Ayre, K.G. Lalitha, K. Ruckmani, Nilesh Khutle, Harshal Pawar, Neha Dand, Vijaya C (138-148).
Keeping in view the standpoint of quality by design, the current work was undertaken to optimize the process parameters in spray drying involved in the production of nanoparticles of famotidine (FAM), a drug with low oral bioavailability. Statistical experimentation approach using 23 full factorial design was utilized to optimize the spray drying process variables. Polymeric PLGA nanoparticles of FAM were formulated employing spontaneous emulsification-solvent diffusion technique. The critical process parameters (CPPs) chosen were the inlet temperature, the feed rate of the liquid and the aspiration flow rate. The influence of these CPPs on the critical quality attributes (CQAs) like % yield of the dried nanoparticles, was studied. Predicted conditions for maximum yield were: inlet temperature 150 °C, feed flow rate 4.5mL/min and aspiration airflow rate at 1490rpm which led to a yield of 52.6±0.4%. The spray dried nanoparticles were characterized for yield, size, zeta potential, morphology, in vitro drug release and mucoadhesion ability. A comparative analysis of the formed nanoparticles was done with the plain drug and excipients using XRD, DSC and FTIR techniques. The average particle size of the dried nanoparticles was found to be 324±4nm. The polydispersity index was 0.739±0.085. The release of drug from the polymeric nanoparticles followed Higuchi square root kinetics. Thus the use of statistical designing of experiment in the domain of the optimization of spray drying technique was proved to be effective to obtain spray dried nanoparticles of FAM with an appreciable yield.

Chitosan Nanoparticles as Vehicle for Prolonged Ocular Delivery of Ofloxacin by Vijaya C, Bhaskara Rao Bandaru, K. Senthilkumar, A. Babu Thandapani (149-156).
Ofloxacin is a synthetic broad-spectrum fluroquinolone antibiotic, frequently used for the treatment of ocular infections. In the present study, ionic gelation technique was employed as the method of preparation of ofloxacin loaded chitosan nanoparticles using different concentrations of chitosan and sodium tripolyphosphate (TPP) and the potential of these nanoparticles in sustained ocular drug delivery was investigated. Different drug-polymer ratios were used to prepare five batches of nanoparticles at two concentrations of chitosan solutions (0.2% w/v and 0.4% w/v). The formulated nanoparticles were evaluated for morphology by Scanning Electron Microscopy, and subjected to particle size analysis and zeta potential measurement by Zetasizer. Drug content, encapsulation efficiency and in vitro drug release studies were also done. LCS-OF3 nanoparticles prepared with 0.2% chitosan solution and drug-chitosan ratio 3:1 were checked for pH and osmolality for their suitability in in vivo study after that subjected to in vivo drug release study in rabbits, the results of which clearly indicate the controlled and prolonged drug release from LCS-OF3 nanoparticles when compared to that from commercially available ofloxacin eye drops.

The investigation was aimed at developing polymeric micellar ocular delivery system of miconazole nitrate for efficient management of fungal endophthalmitis. Drug loaded micelles of tri-block copolymers Pf 127 and Pf 68 were prepared by solvent evaporation method. The polymeric micelles (F1 to F12) were assessed for entrapment efficiency, micelle size and in vitro permeation. Formulation F2 with the lowest micelle size of 80.5 nm, least polydispersity value of 0.105, highest entrapment efficiency of 89.25±2.00% and a cumulative drug permeation of 92.28±1.95% in 8h, was selected to develop pH-sensitive micelles loaded carbopol in situ gel. Of the five gel formulations screened (G1-G5), G5 was selected on the basis of optimum physicochemical characteristics. A comparative ex vivo transcorneal permeation study between G5, F2 and pure drug, using intact goat cornea analyzed the ability of formulations to achieve target concentration. While F2 achieved the target concentration (96.59±0.65%) in 6 hrs, G5 showed sustained release and achieved target concentration (96.9±1.27%) in 8 hrs in contrast to 26.96±0.75% permeation achieved by pure drug solution in 8 hrs. The results indicated controlled permeation of drug across the cornea 8 hrs via optimized in situ formulation G5. Zero score in HET CAM test indicated non-irritant property of G5 and histological studies revealed no visual signs of corneal tissue damage suggesting ocular safety of the optimized in situ gel.