Jayanta Kumar Pandit

Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells

During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review.

Mucoadhesive Chitosan-Coated Cationic Microemulsion of Dexamethasone for Ocular Delivery: In Vitro and In Vivo Evaluation

ABSTRACT Purpose: Dexamethasone (DXN) is an effective anti-inflammatory drug in the treatment of acute and chronic eye disease such as uveitis. However, its low aqueous solubility limits its clinical usefulness. The purpose of this study was to investigate the mucoadhesive chitosan-coated cationic microemulsions (CH-MEs) for ophthalmic delivery of DXN to treat uveitis. Materials and methods: The pseudo-ternary phase diagrams were developed and various MEs were prepared using isopropyl myristate as oil, Tween 80 as a surfactant, propylene glycol as a co-surfactant and distilled water. MEs were prepared and coated with chitosan by the dropwise addition of chitosan solution in the ME dispersion. Physicochemical parameters (globule size, zetapotential, drug content, viscosity, refractive index and pH), mucoadhesive properties and the in vitro release of MEs were studied. The in vivo efficacy of prepared formulations and the marketed drug solution were studied by administering them topically to endotoxin-induced uveitis rabbit model. Results: All formulations displayed an average globule size less than 200 nm and a positive surface charge. The developed CH-MEs showed acceptable physico-chemical behavior, good mucoadhesive properties, good stability for three months and exhibited sustained drug release. In vivo studies in rabbit eye showed a marked improvement in the anti-inflammatory activity of mucoadhesive CH-ME-treated eye compared with a marketed suspension formulation in a uveitis-induced rabbit eye model. Conclusion: The developed CH-MEs are a viable alternative to conventional eye drops for its ability to enhance bioavailability through its longer precorneal residence time and its ability to sustain the release of the drug.

Sodium Alginate Based Mucoadhesive System for Gatifloxacin and Its In Vitro Antibacterial Activity

The objective of this study was to formulate sodium alginate based ophthalmic mucoadhesive system of gatifloxacin and its in vitro antibacterial potential on pathogenic microorganisms, Staphylococcus aureus and Escherichia coli. Sodium carboxymethylcellulose (NaCMC) was added to the formulations to enhance the gel bioadhesion properties. The prepared formulations were evaluated for their in vitro drug release, gelation behaviour, rheological behavior, and mucoadhesion force. All formulations in non-physiological and physiological condition showed pseudo plastic behavior. Increase in the concentration of sodium alginate and sodium CMC enhanced the mucoadhesive force significantly. In vitro release of gatifloxacin from the system in simulated tear fluid (STF, pH – 7.4), was influenced significantly by the properties and concentration of sodium alginate, NaCMC. Significant reduction in total bacterial count was observed between control and treatment groups with both the test organisms.

Multi-Unit Floating Alginate System: Effect of Additives on Ciprofloxacin Release

In an attempt to fabricate floating beads of ciprofloxacin, drugloaded alginate beads were prepared by simultaneous external and internal gelation. The effect of blending of alginate with gellan, hydroxypropyl methylcellulose, starch, and chitosan on the bead properties were evaluated. Beads were spherical with incorporation efficiency in the range of 52.81 ± 2.64 to 78.95 ± 1.92%. Beads exhibited buoyancy over a period of 7–24 hr based on the formulation variables. In vitro release of ciprofloxacin from the alginate beads in simulated gastric fluid (SGF) (0.1 N HCl, pH 1.2), was influenced significantly (p < 0.001) by the properties and concentration of additives. Among the polymers incorporated into alginate beads. Hydroxy propyl methylcellulose (HPMC) provided an extended release over 7 hr. The drug release predominately followed Higuchis square root model.

Effect of Penetration Enhancers on the Transdermal Delivery of Bupranolol Through Rat Skin

Bupranolol (BPL) is a suitable drug candidate for transdermal drug delivery system development based on its favorable physicochemical and pharmacokinetic properties. The effect of different penetration enhancers on the permeation of BPL across rat skin was studied using side-by-side diffusion cells. 2-pyrrolidone (PY), 1-methyl-2-pyrrolidone (MPY), and propylene glycol (PG) at various concentrations were used as penetration enhancers along with 0.4% w/v aqueous suspension of BPL. Menthol at different concentrations in isopropanol-water (6:4) mixture also was used as an enhancer wherein BPL at 0.4% w/v was completely solubilized. Skin pretreatment studies were carried out with all the above enhancers to understand their role in the penetration enhancement effect. PY and MPY at 5% w/v concentrations increased the permeation of BPL by 3.8- and 2.4-fold, respectively, versus control (p < .01). PG at 10% and 30 w/v concentrations increased the flux of BPL by 2.5- and 5.0-fold, respectively, versus control (p < .001). Menthol at 2% w/v concentration increased the flux of BPL by 3.8-fold (p < .01) and further increase in menthol concentration significantly decreased the flux of BPL. Overall, pyrrolidones and menthol at low concentrations (5% w/v or less) and PG at 30% w/v concentration were effective as penetration enhancers for BPL.

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.

Effect of Aging on the Dissolution Stability of Glibenclamide/β-Cyclodextrin Complex

The effect of aging on the physicochemical stability of glibenclamide (GB)/beta-cyclodextrin (CD) systems and tablets made with CD-complexed GB was studied. Infrared (IR) spectrometry and X-ray diffraction analyses showed that the properties of the products were unaffected even after a storage period of 4 years, except that the crystallinity of GB/CD physical mixture was decreased with aging. The dissolution rate of the kneaded mixture, inclusion complex, and tablets made with the inclusion complex were unaffected on storage for 4 years. Thus, the age-related dissolution problems of GB can be overcome by utilizing the GB/CD complex in the tablet dosage form.

Low molecular mass chitosan as carrier for a hydrodynamically balanced system for sustained delivery of ciprofloxacin hydrochloride

Low molecular mass chitosan as carrier for a hydrodynamically balanced system for sustained delivery of ciprofloxacin hydrochloride Chitosan has become a focus of major interest in recent years due to its excellent biocompatibility, biodegradability and non-toxicity. Although this material has already been extensively investigated in the design of different types of drug delivery systems, it is still little explored for stomach specific drug delivery systems. The objective of the present investigation was to explore the potential of low molecular mass chitosan (LMCH) as carrier for a hydrodynamically balanced system (HBS) for sustained delivery of water soluble drug ciprofloxacin hydrochloride (CP). Various formulations were prepared by physical blending of drug and polymer(s) in varying ratios followed by encapsulation into hard gelatin capsules. All the formulations remained buoyant in 0.1 mol L-1 HCl (pH 1.2) throughout the experiment. Effect of addition of xanthan gum (XG) or ethyl cellulose (EC) on drug release was also investigated. Zero order drug release was obtained from the formulations containing LMCH alone or in combination with XG, and in one instance also with EC. Our results suggest that LMCH alone or in combination with XG is an excellent material for stomach specific sustained delivery of CP from hydrodynamically balanced single unit capsules. Kitozan male molekulske mase kao nosač hidrodinamički uravnoteženog sustava za usporenu isporuku ciprofloksacin hidroklorida Zbog svoje biokompatibilnosti, biorazgradljivosti i netoksičnosti kitozan je vrlo interesantan istraživačima u području farmaceutske tehnologije. Najviše se upotrebljavao u dizajniranju različitih sustava za isporuku lijekova ali vrlo malo za sustave za specifičnu isporuku u želucu. Cilj ovog rada bio je ispitati mogućnost upotrebe kitozana male molekulske mase (LMCH) kao nosača u hidrodinamički balansiranom sustavu (HBS) za usporenu isporuku vodotopljivog lijeka ciprofloksacin hidroklorida (CP). Pripravljene su različite formulacije stvaranjem fizičke smjese lijeka i polimera u različitim omjerima, koje su potom kapsulirane u želatinske kapsule. Svi su pripravci za vrijeme cijelog eksperimenta ostali plutati u 0,01mol L1 HCl (pH 1,2). Ispitivan je i učinak ksantan gume (XG) ili etilceluloze (EC) na oslobađanje lijeka. Oslobađanje lijeka nultog reda postignuto je iz formulacija koje sadrže samo LMCH ili LMCH u kombinaciji sa XG i u jednom slučaju s EC. Dobiveni rezultati pokazuju da je LMCH, sam ili u kombinaciji sa XG, izvrstan materijal za sustave za specifičnu isporuku CP iz hidrodinamički balansiranih kapsula.

Effect of hydroxypropyl-β-cyclodextrin on the ocular bioavailability of dexamethasone from a pH-induced mucoadhesive hydrogel.

Purpose: Dexamethasone (DXN) is an effective anti-inflammatory drug in the treatment of acute and chronic eye disease such as uveitis. It is relatively lipophilic and permeates biological membranes quite easily. However, its low aqueous solubility limits its clinical usefulness. To circumvent this problem Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as solubilizer and penetration enhancer for DXN. The purpose of this study was to develop HP-β-CD based pH-induced mucoadhesive hydrogel for ophthalmic delivery of DXN to treat uveitis. Materials and methods: The formation of inclusion complex of DXN with HP-β-CD was characterized in solution and solid states by phase solubility, X-ray diffractometry and IR spectrum analyses. To improve ocular retention and sustained action Carbopol 980 NF and sodium carboxymethylcellulose (NaCMC) were added to the formulations as phase transition and mucoadhesive agents, respectively. Results: The HP-β-CD-based hydrogel system enhanced the solubility of DXN and the apparent stability constant (k′) of the DXN-HP-β-CD inclusion complex was found to be 258.62 M−1. The optimum concentrations of Carbopol 980NF and NaCMC for the mucoadhesive hydrogel were 0.2% (w/v) and 0.4% (w/v), respectively. This mucoadhesive hydrogel could flow freely under non-physiological condition and showed the character of pseudoplastic fluid under both physiological and non-physiological conditions. In vitro release of DXN from the HP-β-CD complex in simulated tear fluid (STF, pH− 7.4), was influenced significantly by the properties and concentration of Carbopol and NaCMC. In vivo studies in rabbit eye showed a marked improvement in anti-inflammatory activity of mucoadhesive hydrogel-treated eye compared with a marketed solution formulation in a uveitis-induced rabbit eye model. Conclusion: The developed HP-β-CD-based mucoadhesive system is a viable alternative to conventional eye drops of DXN due to its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain the release of the drug.

Chitosan inserts for periodontitis : Influence of drug loading, plasticizer and crosslinking on in vitro metronidazole release

Chitosan inserts for periodontitis: Influence of drug loading, plasticizer and crosslinking on in vitro metronidazole release Chitosan based metronidazole (MZ) inserts were fabricated by the casting method and characterized with respect to mass and thickness uniformity, metronidazole loading and in vitro metronidazole release kinetics. The fabricated inserts exhibited satisfactory physical characteristics. The mass of inserts was in the range of 5.63 ± 0.42 to 6.04 ± 0.89 mg. The thickness ranged from 0.46 ± 0.06 to 0.49 ± 0.08 mm. Metronidazole loading was in the range of 0.98 ± 0.09 to 1.07 ± 0.07 mg except for batch CM3 with MZ loading of 2.01 ± 0.08 mg. The inserts exhibited an initial burst release at the end of 24 h, irrespective of the drug to polymer ratio, plasticizer content or cross-linking. However, further drug release was sustained over the next 6 days. Cross-linking with 10% (m/m) of glutaraldehyde inhibited the burst release by ~30% and increased the mean dissolution time (MDT) from 0.67 to 8.59 days. The decrease in drug release was a result of reduced permeability of chitosan due to cross-linking. Kitozanski umetci za periodontitis: Utjecaj količine lijeka, plastifikatora i umrežavanja na oslobađanje metronidazola in vitro Umetci metronidazola na bazi kitozana načinjeni su kasting metodom. Proučavana je ujednačenost mase i debljine, količina ljekovite tvari i kinetika oslobađanja metronidazola in vitro. Fizičke karakteristike umetaka bile su zadovoljavajuće: masa je bila u rasponu od 5,63 ± 0,42 - 6,04 ± 0,89 mg, debljina od 0.46 ± 0.06 - 0.49 ± 0.08 mm, količina metronidazola od 0,98 ± 0,09 - 1,07 ± 0,07 mg osim u pripravku CM3 s MZ 1,07 ± 0,07 mg. Nakon 24 h, neovisno o omjeru ljekovite tvari i polimera, količini plastifikatora ili umrežavanju, dio metronidazola se naglo oslobodio iz svih umetaka. Međutim, daljnje je oslobađanje bilo polagano, tijekom 6 dana. Umrežavanje s 10% (m/m) otopinom glutaraldehida spriječilo je naglo oslobađanje za ~30% i povećalo srednje vrijeme oslobađanja (MDT) s 0,67 na 8,59 dana. Smanjenje u oslobađanju ljekovite tvari posljedica je smanjenja permeabilnosti umreženog kitozana.