Pharmaceutical Nanotechnology (v.3, #2)

Editorial by Ijeoma Uchegbu (83-84).

Micro- and Nano-particulate Strategies for Antigen Specific Immune Tolerance to Treat Autoimmune Diseases by Naihan Chen, Kevin J. Peine, Eric M. Bachelder, Kristy M. Ainslie (85-100).
An improper immune response towards a self-antigen can result in an autoimmune disease. Commonly these diseases are treated with therapies that suppress overall immune responses, which can lead to increased risk of infection and cancer. A more specific method would be to induce immune tolerance in an antigen specific manner. This is much like traditional vaccines that have antigen specificity towards the pathogen they are forming protection. This antigen specific protection is called immune tolerance and has been accomplished by introducing soluble antigen to mucosal routes (e.g. oral, nasal or sublingual). Unfortunately, this approach has shown limited success clinically. Nano and microparticles (MPs) have recently been applied as delivery vehicles to help improve efficacy in immune tolerance. MPs can increase the solubility and circulation of cargo and passively target macrophages and dendritic cells. Fabrication of MPs with diseaseassociated antigens has limited disease progression in animal models of Multiple Sclerosis, Type 1 Diabetes, and Rheumatoid Arthritis, which has corresponded to an antigen specific decrease in inflammatory responses. The use of MPs to induce antigen specific tolerance can limit the current therapeutic shortfalls such as adverse drug side effects and blanket suppression of the immune system, which can lead to an overall significant increase in patient quality of life.

Ibuprofen-loaded Acrylate Polymeric Nanosuspensions: Characterization, in vitro and in vivo Anti inflammatory Activity by Bhavani Boddeda, K. Mohan, G. Jhansi, A. Harani, J. Vijaya Ratna, Y. Srinivasa Rao (101-110).
Background: Ibuprofen (IBU), drug choice of non-steroidal anti-inflammatory and analgesic, which were formulated in nanosuspension dosage to improve its therapeutic efficacy. Objective: The aim of the study is to develop and evaluate sustained release ibuprofen nanosuspension by using Eudragit RL100 polymer using preliminary optimized ratio of drug to polymer. Method: Nano-precipitation method was used to prepare IBU nanosuspension. Type of surfactant or stabilizer (Formulation variable) and stirring time (Process variable) were varied to optimize the formulation. Characterization of the nanosuspension was performed by measuring particles size, zeta potential, drug entrapment efficiency, drug loading capacity and in-vitro drug release studies. In vivo pharmacodynamic studies were also carried out on rats. Results: Drug:polymer (1:5) was found to be effective and optimized ratio for further studies. On the basis of result out of F1-F10 formulations, F2 showed, smallest particle size of 240 nm, zeta potential 21.2 mV, entrapment efficiency of 74.92%. SEM image showed that the nanoparticles were spherical in shape with smooth surface. FTIR showed no significant interactions between Eudragit and drug even after encapsulation. In vitro release from the nanosuspension showed biphasic sustained release the drug action. From the in vivo (anti-inflammatory activity) studies revealed that prepared nanosuspension sustained its action for longer period of time. Conclusion: Thus, it can be concluded that IBU loaded nanosuspension considered useful approach for sustained drug release and reduce dosing frequency.

Aim: The objective of the present research work was to formulate a sustained release Ibuprofen nanoparticles to reduce side effects and dosing frequency and to investigate the effect of various formulation variables such as stirring speed, organic: aqueous phase ratio, type and concentration of stabilizer on the preparation of optimized formulation of Ibuprofen loaded ethyl cellulose nanoparticles by nanoprecipitation method. Methodology: Ibuprofen loaded Ethyl cellulose nanoparticles were prepared by nanoprecipitation technique. The obtained nanoparticles were characterized for surface morphology, average particle size, zeta potential and evaluated for percentage yield, drug content, entrapment efficiency, drug loading and in vitro drug release. Results: The final optimized parameters were found to be 700rpm, 1:10 organic: aqueous ratio and 0.6% W/V of stabilizer (Tween-80, Tween-20 and PVA). On comparison of total 9 formulations C3 formulation prepared by using 0.6%w/v PVA as a stabilizer was found to be the best with highest entrapment efficiency (78%), greater stability (-49.8mV), with mean particle diameter of 586.9nm and it was able to sustain the release for about 9 hours. The SEM images of C3 formulation revealed the particles were of smooth surface with spherical morphology and low porosity. Conclusions: Based on the results the final optimized parameters were found to be 700rpm, 1:10 organic: aqueous ratio and 0.6%W/V of stabilizer (PVA) for the preparation of ibuprofen nanoparticles by nanoprecipitation technique.

Nanostructured Lipid Carriers for Topical Delivery of An Anti-Acne Drug: Characterization and ex vivo Evaluation by Sweety Kumari, Deepti Pandita, Neelam Poonia, Viney Lather (122-133).
The poor water solubility of azelaic acid, a polyphenolic compound, used in treatment of acne and rosacea poses limitations in its topical delivery. To overcome these issues, azelaic acid loaded nanostructured lipid carriers (NLCs) were prepared by solvent diffusion-solvent evaporation method for enhancing their dermal retention and moreover, slow release of drug from NLCs can avoid side effects associated with its usage. The optimized formulation was characterized for size, morphology and zeta potential. Mean particle size of azelaic acid loaded NLCs was 81.57±9.6 nm with low poly dispersity index (PDI) i.e. 0.208±0.021 and high zeta potential of -29.3±1.21 mV was obtained. Results of transmission electron microscopy (TEM) imaging demonstrated spherical shape of NLCs with uniform surface. Ex vivo permeation studies of azelaic acid loaded NLCs gel showed biphasic drug release pattern with initial burst release followed by sustained release and also led to slower release profiles compared to plain drug loaded gel and drug solution i.e 21.06±0.99, 38.71±1.47 and 78.79±2.52% of the drug was permeated from NLCs gel, plain gel and drug solution, respectively with 51.6±0.74, 95.25±1.23 and 184.59 ?g/cm2/hr flux values respectively. Further in skin retention studies, significant retention of azelaic acid from the NLCs gel i.e. 63.96±4.56% in the rat skin was observed than the drug solution and plain drug loaded gel which were observed to be only 4.78±1.1% and 15.12±3.2% respectively. The formulation stability was assessed at two different temperatures and NLCs were found to be stable. The results conclude that the developed NLCs have enormous potential to improve the penetration of the azelaic acid through stratum corneum with utmost retention in the skin which is the pre-requisite for the topically applied formulations for the management of skin diseases and the avoidance of systemic adverse effects associated with its usage.

Background: Noscapine is a phthalideisoquinoline alkaloid obtained from opium poppy found to have anti cancer properties. The compound is well-tolerated with low toxicity profile but its clinical translation against cancer is limited due to poor dissolution characteristics, and substantial first-pass metabolism. Objective: This paper deals with the preparation, optimization and characterization of poly(D,L-lactide) nanoparticles encapsulating noscapine for its intended use as anticancer formulation. Methods: Noscapine encapsulation in biodegradable poly(D,L-lactide) nanoparticles was done by employing emulsion solvent diffusion method. A number of variables such as organic solvent, its ratio with aqueous phase, drug to polymer ratio, mixing speed were optimized. To investigate the effect of process variables on mean particle size, drug loading and entrapment efficiency of several stabilizers were also screened. In vitro noscapine release was studied using dialysis bag method. Final formulation was freeze dried for long term storage for which a number of lyoprotectants were screened. Results: It was observed that stabilizer, solvent, drug to polymer ratio, surfactant concentration, organic/aqueous phase volume ratio and stirring speed influence nanoparticle size significantly whereas drug loading and entrapment efficiency were significantly influenced by stabilizers, solvents, drug to polymer ratio and surfactant concentration. Optimized noscapineloaded PLA nanoparticles were found to be of spherical shape with mean size of 190.8±3.5nm. Drug loading and entrapment efficiency were 7.2±0.2% and 70.3±1.7% respectively. Noscapine release pattern from the prepared PLA nanoparticles was found to be biphasic with an initial burst followed by sustained release. Mannitol provided best lyoprotection to freeze dried noscapine PLA nanoparticles. Conclusion: Noscapine can be successfully formulated as poly(D,L-lactide) nanoparticles with good drug loading and encapsulation efficiency whose prolonged storage can be ensured with freeze drying.