Ramesh C. Nagarwal

Polymeric nanoparticulate system: a potential approach for ocular drug delivery.

Various efforts in ocular drug delivery have been made to improve the bioavailability and to prolong the residence time of drugs applied topically onto the eye. The potential use of polymeric nanoparticles as drug carriers has led to the development of many different colloidal delivery vehicles. Drug loaded polymeric nanoparticles (DNPs) offer several favorable biological properties, such as biodegradability, nontoxicity, biocompatibility and mucoadhesiveness. These submicron particles are better than conventional ophthalmic dosage forms to enhance bioavailability without blurring the vision. DNPs have been shown to be amenable to targeting of the drug to the site of action, leading to a decrease in the dose required and a decrease in side effects. Additionally, DNPs can be fabricated by simple techniques with better physical stability than liposomes. This unique combination of properties makes DNPs a novel polymeric drug delivery device, which fulfils the requirements for ophthalmic application. This review discusses the polymeric nanoparticles, physiochemical characterization, fabrication techniques, therapeutic significances, patented technology of nanoparticles and future possibility in the field of ocular drug delivery.

Chitosan coated sodium alginate–chitosan nanoparticles loaded with 5-FU for ocular delivery: In vitro characterization and in vivo study in rabbit eye

The objective of the study was to develop chitosan (CH) coated sodium alginate-chitosan (SA-CH) nanoparticles, i.e. CH-SA-CH NPs loaded with 5-FU for ophthalmic delivery. Drug loaded nanoparticles (DNPs) were prepared by ionic gelation technique using sodium alginate (SA) and chitosan (CH) and then suspended in chitosan solution. The mean size of nanoparticles and morphology were characterized by dynamic light scattering, scanning electron microscopy, atomic force microscopy and zeta potential. The in vitro release was studied by dialysis membrane technique. The size and drug encapsulation efficiency were dependent on molar ratio of SA and CH. The size of SA-CH nanoparticles was significantly increased with changed morphology after CH coating. SA-CH nanoparticles did not show any interaction with mucin while an enhanced viscosity was observed on coating of nanoparticles with CH. CH-SA-CH DNPs presented a sustained release of 5-FU compared to the 5-FU solution with high burst effect. In vivo study in rabbit eye showed significantly greater level of 5-FU in aqueous humor compared to 5-FU solution. The enhanced mucoadhesiveness of CH-SA-CH DNPs results in higher bioavailability as compared to the uncoated nanoparticles. Optimized formulation was found non-irritant and tolerable when tested by modified Draize test in rabbit eye.

Codrug: An efficient approach for drug optimization

Codrug or mutual prodrug is an approach where various effective drugs, which are associated with some drawbacks, can be modified by attaching with other drugs of same or different categories directly or via a linkage. More appropriately one can say combining two different pharmacophores with similar or different pharmacological activities elicit synergistic action or help to target the parent drug to specific site/organ/cells respectively. This approach is commonly used to improve physicochemical, biopharmaceutical and drug delivery properties of therapeutic agents.

In Vitro Release Kinetics and Bioavailability of Gastroretentive Cinnarizine Hydrochloride Tablet

An oral sustained release dosage form of cinnarizine HCl (CNZ) based on gastric floating matrix tablets was studied. The release of CNZ from different floating matrix formulations containing four viscosity grades of hydroxypropyl methylcellulose, sodium alginate or polyethylene oxide, and gas-forming agent (sodium bicarbonate or calcium carbonate) was studied in simulated gastric fluid (pH 1.2). CNZ release data from the matrix tablets were analyzed kinetically using Higuchi, Peppas, Weibull, and Vergnaud models. From water uptake, matrix erosion studies, and drug release data, the overall release mechanism can be explained as a result of rapid hydration of polymer on the surface of the floating tablet and formation of a gel layer surrounding the matrix that controls water penetration into its center. On the basis of in vitro release data, batch HP1 (CNZ, HPMC-K100LV, SBC, LTS, and MgS) was subjected to bioavailability studies in rabbits and was compared with CNZ suspension. It was concluded that the greater bioavailability of HP1 was due to its longer retention in the gastric environment of the test animal. Batch no. HP1 of floating tablet in rabbits demonstrated that the floating tablet CNZ could be a 24-h sustained release formulation.

Modified PLA nano in situ gel: a potential ophthalmic drug delivery system.

A novel nano in situ gel forming system of 5-Fluorouracil (5-FU) was investigated for its potential use for conjunctival/corneal squamous cell carcinoma (CCSC). The study was conducted in two steps, in the first step PLA nanoparticles were prepared and characterized; in the second step the drug loaded PLA nanoparticles were dispersed in sodium alginate solution yielding the modified nano in situ system, which were evaluated in rabbit eye. Size and morphology of prepared PLA particles were verified by using dynamic light scattering (DLS), atomic force microscope (AFM) and scanning electron microscope (SEM). In vitro and in vivo study of free 5-FU, PLA nanoparticles and modified nano in situ system were conducted in simulated tear fluid and in rabbit eye respectively. PLA nanoparticles were in size range of 128-194 nm with spherical shape and smooth surface with narrow size distribution. No polymer drug interaction was found as confirmed by FTIR, NMR and DSC. XRD of PLA nanoparticles confirmed that 5-FU was present in the crystalline state. In vitro experiments indicated a diffusion controlled release of 5-FU from both PLA nanoparticles and modified nano in situ system with high burst effect. Modified nano in situ gel system (MNS) significantly increased the Cmax and AUC0-8 in aqueous humor as compared to 5-FU solution and PLA nanoparticles. Higher 5-FU level in aqueous humor was possibly because of increased retention time of gel matrix-embedded drug loaded nanoparticles. Overall results showed the potential of MNS for ophthalmic delivery in the therapy of CCSC.

Nanocrystal Technology in the Delivery of Poorly Soluble Drugs: An Overview

Extensive attempts to overcome problems related to solubility of drugs for maximizing bioavailability at targeted sites in the body have been made. The issue of drug solubility appears to attract the continued interest of pharmaceutical manufacturers. In this context, nanocrystallization has emerged as an important tool. In the present review, the authors discuss the advantages of nanocrystallized drugs and examine the products available in the market as well as drugs in the pipeline using nanocrystal-based formulations, which are being developed by pharmaceutical companies for drug delivery.

Fabrication of Lomustine Loaded Chitosan Nanoparticles by Spray Drying and in Vitro Cytostatic Activity on Human Lung Cancer Cell Line L132

This study was aimed to develop lomustine loaded chitosan nanoparticles using a homogenization and spray drying technique. Effect of crosslinking agents (sodium tripolyphosphate (TPP), and sodium hexametaphosphate (HMP)) were studied on the leaching of drug, water uptake of hydrogels, drug release from matrix and its mechanism. N anoparticles were obtained in the average size range of 111±16.2 to 942±11.7 nm with polydispersity index (PDI) from 0.116±0.039 to 0.517±0.037. Zeta potential of nanoparticles was ranged from 29.0±1.1 to 56.0±1.1 mV. The % encapsulation ef fi ciency of nanoparticles ranged between 58±0.88% and 96±0.51%.nanoparticles were coated with PEG 6000 to modulate drug release. Swelling index of chitosan-TPP and chitosan-TPP-PEG nanoparticles was about 428% and 350% over the 4 h and it was more (about 465% and 395%) for chitosan-HMP and chitosan-HMP-PEG nanoparticles. Drug release was sustained and diffusion controlled. Optimized formulation was tested for anticancer activity and drug retention study. Cytotoxicity on human lung cancer cell line L132 was studied by trypan blue dye exclusion test. Drug loaded nanoparticles killed L132 cells more ef fi ciently than the corresponding drug alone (p< 0.05). Due to the increased surface area lomustine loaded TPP and HMP crosslinked chitosan nanoparticles showed better anticancer activity.