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CURATOR
A pinboard by
Subham Banerjee

Young Scientist, Centre for Bio-design, Translational Health Science & Technology Institute (THSTI).

PINBOARD SUMMARY

Nanostructured Delivery of Anti-TB drugs.

Rifampicin (RIF) and Isoniazid (INH) are two major first-line oral antitubercular drugs (ATDs) that have gained a broad acceptance for the treatment of multi-drug resistance tuberculosis (MDR-TB). However, a major concern related to the oral delivery of RIF is associated with the rapid hydrolysis and interaction of RIF, as a result of INH-catalysed degradation under stomach acidic pH environment. This phenomenon is mediated by the hydrolytic reaction of 3-formyl rifamycin, an acid degradation derivative of RIF, with INH, to form an insoluble iso-nicotinyl hydrazone. This causes a direct decline in the available RIF dose below the sub-therapeutic level, thereby diminishing its therapeutic efficacy. We hypothesized that encapsulation of these important ATDs into lipid nanoparticle formulations (LNFs) may avoid INH-mediated chemical degradation and interaction of RIF in a gastric environment at pH-1.2. For this purpose, we evaluated two promising lipid nanoformulations, viz., solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for drug encapsulation. In this article, we report on the design, synthesis and comparative evaluation of SLN- and NLC-based formulations of both INH and RIF. A multiple emulsion method with a modified two-step emulsification strategy was adopted to design LNFs, in order to get homogeneous, discrete, uniformly sized, stable LNFs, with satisfactory in vitro performance. This strategy of nanoencapsulation substantially prolonged release of encapsulated RIF in a simulated gastric environment, and improved its chemical stability in presence of INH. In vitro cell culture studies showed a well-quantifiable uptake of LNFs in a macrophage cell line. Overall, these evaluations provided promising results for establishing the drug delivery potential of such formulations for applications to TB therapy.

7 ITEMS PINNED

Nanosizing techniques for improving bioavailability of drugs.

Abstract: The poor solubility of significant number of Active Pharmaceutical Ingredients (APIs) has become a major challenge in the drug development process. Drugs with poor solubility are difficult to formulate by conventional methods and often show poor bioavailability. In the last decade, attention has been focused on developing nanocrystals for poorly water soluble drugs using nanosizing techniques. Nanosizing is a pharmaceutical process that changes the size of a drug to the sub-micron range in an attempt to increase its surface area and consequently its dissolution rate and bioavailability. The effectiveness of nanocrystal drugs is evidenced by the fact that six FDA approved nanocrystal drugs are already on the market. The bioavailabilities of these preparations have been significantly improved compared to their conventional dosage forms. There are two main approaches for preparation of drug nanocrystals; these are the top-down and bottom-up techniques. Top-down techniques have been successfully used in both lab scale and commercial scale manufacture. Bottom-up approaches have not yet been used at a commercial level, however, these techniques have been found to produce narrow sized distribution nanocrystals using simple methods. Bottom-up techniques have been also used in combination with top-down processes to produce drug nanoparticles. The main aim of this review article is to discuss the various methods for nanosizing drugs to improve their bioavailabilities.

Pub.: 13 Jun '17, Pinned: 19 Jun '17

Raman imaging of cellular uptake and studies of silver nanoparticles effect in BJ human fibroblasts cell lines.

Abstract: Silver nanoparticles (AgNPs) have been widely studied for their beneficial antimicrobial effect and have been considered by some to be a safe ingredient, as penetration of metal nanoparticles through the skin in vivo has not been proven. However, AgNPs are becoming a commonly applied nanomaterial for surface modifications of medical products which come into contact with damaged skin. In our experiments, we tested two commercially available AgNPs samples manufactured by electrolysis. AFM was used to characterize tested AgNPs morphology and their mean particle size which was assessed as 30.6nm and 20.4nm. An important mechanism of AgNPs cytotoxicity is generation of reactive oxygen species (ROS), chemically reactive species containing oxygen. Although ROS occur in cell metabolism naturally, their overproduction can induce oxidative stress - imbalance between production and antioxidant defenses. This can be associated with cytotoxicity and DNA damage. Conventional in vitro tests were used to evaluate the cytotoxic potential and DNA damage in BJ human fibroblasts cell lines. We found that both tested AgNPs samples induced ROS generation and caused the DNA damage in fibroblasts. One of the key concerns about the association with cytotoxic or genotoxic responses of nanoparticles is the capability of these materials to penetrate through cellular membrane. Cellular uptake studies were performed using Raman imaging as a label-free microscopic technique. In combination with a univariate image analysis, results demonstrate cellular uptake and distribution of the AgNPs which were taken up by BJ cells within 24h of incubation in a growth medium. The study demonstrates the potential of Raman imaging to unambiguously identify and localize AgNPs in fixed cells.

Pub.: 13 Jun '17, Pinned: 19 Jun '17

Development of semisolid self-microemulsifying drug delivery systems (SMEDDSs) filled in hard capsules for oral delivery of aciclovir.

Abstract: The study aimed to develop semisolid self-microemulsifying drug delivery systems (SMEDDSs) as carriers for oral delivery of aciclovir in hard hydroxypropylmethyl cellulose (HPMC) capsules. Six self-dispersing systems (SD1-SD6) were prepared by loading aciclovir into the semisolid formulations consisting of medium chain length triglycerides (lipid), macrogolglycerol hydroxystearate (surfactant), polyglyceryl-3-dioleate (cosurfactant), glycerol (hydrophilic cosolvent), and macrogol 8000 (viscosity modifier). Their characterization was performed in order to identify the semisolid system with rheological behaviour suitable for filling in hard HPMC capsules and fast dispersibility in acidic and alkaline aqueous media with formation of oil-in-water microemulsions. The optimal SMEDDS was loaded with aciclovir at two levels (2% and 33.33%) and morphology and aqueous dispersibility of the obtained systems were examined by applying light microscopy and photon correlation spectroscopy (PCS), respectively. The assessment of diffusivity of aciclovir from the SMEDDSs by using an enhancer cell model, showed that it was increased at a higher drug loading. Differential scanning calorimetry (DSC) analysis indicated that the SMEDDSs were semisolids at temperatures up to 50°C and physically stable and compatible with HPMC capsules for 3 months storage at 25°C and 4°C. The results of in vitro release study revealed that the designed solid dosage form based on the semisolid SMEDDS loaded with the therapeutic dose of 200mg, may control partitioning of the solubilized drug from in situ formed oil-in-water microemulsion carrier into the sorrounding aqueous media, and hence decrease the risk for precipitation of the drug.

Pub.: 18 Jun '17, Pinned: 19 Jun '17