Efficacy Interactions of PEG-DOX-N-acetyl Glucosamine Prodrug Conjugate for Anticancer Therapy.

Present investigation is exploring structure-biocompatibility interaction of tumour targeted polyethylene glycol (PEG) based drug conjugate of doxorubicin using N-acetyl glucosamine as targeting ligand. The synthesized polymer drug conjugate was evaluated for particle size, zeta potential, molecular weight, haemolysis activity, cytotoxicity, protein binding and in vitro receptor (lectin) binding study. The particle size of synthesized conjugate was observed to be around 30 nm with polydispersability index of 0.213 indicating mono-disperse particles. Fluorescence quenching assay addressed relatively lower binding interactions of polymer drug conjugate to bovine serum albumin in comparison with free doxorubicin which may be governed to the hydrophilicity of polyethylene glycol and N-acetyl glucosamine. The cell compatibility and haemolysis study showed that PEG drug conjugate was nontoxic and biocompatible, which recommends the suitability of polymer drug conjugates for delivering biological active agents systemically. In vitro ligand-lectin receptor binding assays of synthesized targeted polymer conjugate suggest the possibility of promising interaction of N-acetyl glucosamine in vivo. Thus, the study indicated the suitability of N-acetyl glucosamine anchored targeted polymer drug conjugate in delivering bio-therapeutics for specifically targeting to tumour tissues.

Fabrication of isradipine nanosuspension by anti-solvent microprecipitation-high-pressure homogenization method for enhancing dissolution rate and oral bioavailability.

The aim of this study was to develop a nanosuspension of a highly hydrophobic drug, isradipine (ISR) by combination of anti-solvent microprecipitation and high-pressure homogenization to achieve the superior in vitro dissolution and in vivo pharmacokinetic profile. The nanosuspension was formulated using combination of stabilizers as vitamin E TPGS and sodium lauryl sulfate. The developed nanosuspension was characterized for particle size, shape, and zeta potential. The particle size of the developed ISR nanosuspension was observed to be approximately 538 nm (by laser diffraction) and 469 nm (by photon correlation spectroscopy) with -33.3 mV zeta potential. Scanning electron microscopy study revealed the good correlation with particle size measured by photon correlation spectroscopy and laser diffraction. The X-ray diffraction and differential scanning calorimetry showed that ISR was present as an amorphous state in the lyophilized form of nanosuspension. In vitro dissolution and saturation solubility study showed the dissolution rate of nanosuspensions (98.60 %) and saturation solubility (98.76 µg/ml) compared with the coarse drug (11.53 % and 14.1 µg/ml, respectively) had been significantly enhanced. The pharmacokinetic study showed that the nanosuspension exhibits increased in AUC0-48 by 2.0-fold compared to coarse suspension. Further, there was increased in C max and decreased in t max of ISR nanosuspension compared to coarse suspension of ISR. These studies proved that particle size reduction can influence ISR absorption in gastrointestinal tract and thus nanosuspension technology is responsible for enhancing oral bioavailability in rats.

Design, synthesis and evaluation of N-acetyl glucosamine (NAG)-PEG-doxorubicin targeted conjugates for anticancer delivery.

Efficacy of anticancer drug is limited by the severe adverse effects induced by drug; therefore the crux is in designing delivery systems targeted only to cancer cells. Toward this objectives, we propose, synthesis of poly(ethylene glycol) (PEG)-doxorubicin (DOX) prodrug conjugates consisting N-acetyl glucosamine (NAG) as a targeting moiety. Multicomponent system proposed here is characterized by (1)H NMR, UV spectroscopy, and HPLC. The multicomponent system is evaluated for in vitro cellular kinetics and anticancer activity using MCF-7 and MDA-MB-231 cells. Molecular modeling study demonstrated sterically stabilized conformations of polymeric conjugates. Interestingly, PEG-DOX conjugate with NAG ligand showed significantly higher cytotoxicity compared to drug conjugate with DOX. In addition, the polymer drug conjugate with NAG and DOX showed enhanced internalization and retention effect in cancer cells, compared to free DOX. Thus, with enhanced internalization and targeting ability of PEG conjugate of NAG-DOX has implication in targeted anticancer therapy.

Rice germ oil as multifunctional excipient in preparation of self-microemulsifying drug delivery system (SMEDDS) of tacrolimus.

Surmounting the constraints of limited solubilization efficiency and prime requisite of antioxidant for conventional lipid formulations, the research work explores an edge over formulation utilizing potential applicability of rice germ oil (RGO) as a multifunctional excipient. Self-microemulsifying drug delivery system (SMEDDS) of tacrolimus (TAC) was formulated with RGO, an indigenous source of gamma-oryzanol. Being the same biological source, RGO and rice bran oil (RBO) were compared and it was found that RGO have more solubilization potential for TAC (2.2-fold) as well as higher antioxidant activity (8.06-fold) than the RBO. TAC-SMEDDS was prepared using RGO/Capmul PG8 (2:3) as an oil phase, Cremophore EL as a surfactant, and Transcutol P as a cosurfactant. The approximate particle size of TAC-SMEDDS was found to be 38 nm by dynamic light scattering and 12 nm by small angle neutron scattering. The in vitro dissolution studies showed complete and rapid drug release in 30 min compared to a plain drug (<5%) and marketed capsule (<50%). AUC and C(max) were found to be 45.05 ± 15.64 ng h/ml and 3.91 ± 1.2 ng/ml for TAC-SMEDDS, 12.59 ± 5.54 ng h/ml and 0.48 ± 0.12 ng/ml for plain TAC, and 30.23 ± 10.34 ng h/ml and 2.31 ± 0.68 ng/ml for marketed formulation, respectively. The improved pharmacokinetic profile of TAC-SMEDDS is correlating to the dissolution results. Thus, gamma-oryzanol-enriched RGO acts as a potential multifunctional excipient for lipid formulations.