Mohammed Anwar

A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives

In the modern world, a number of therapeutic proteins such as vaccines, antigens, and hormones are being developed utilizing different sophisticated biotechnological techniques like recombinant DNA technology and protein purification. However, the major glitches in the optimal utilization of therapeutic proteins and peptides by the oral route are their extensive hepatic first-pass metabolism, degradation in the gastrointestinal tract (presence of enzymes and pH-dependent factors), large molecular size and poor permeation. These problems can be overcome by adopting techniques such as chemical transformation of protein structures, enzyme inhibitors, mucoadhesive polymers and permeation enhancers. Being invasive, parenteral route is inconvenient for the administration of protein and peptides, several research endeavors have been undertaken to formulate a better delivery system for proteins and peptides with major emphasis on non-invasive routes such as oral, transdermal, vaginal, rectal, pulmonary and intrauterine. This review article emphasizes on the recent advancements made in the delivery of protein and peptides by a non-invasive (peroral) route into the body.

Enhanced bioavailability of nano-sized chitosan–atorvastatin conjugate after oral administration to rats

A novel approach to improve the bioavailability and stability of atorvastatin (AT) was developed by constructing a nano-sized polymer-atorvastatin conjugate. Firstly, a novel chitosan-atorvastatin (CH-AT) conjugate was efficiently synthesized through amide coupling reaction. The formation of conjugate was confirmed by (1)H NMR and FT-IR spectrometry. Nano-sized conjugate with a mean size of 215.3±14.2 nm was prepared by the process of high pressure homogenization (HPH). Scanning electron microscopy (SEM) revealed that CH-AT nano-conjugate possess smooth surface whereas X-ray diffraction (XRD) spectra demonstrated amorphous nature of nano-conjugate. Further, CH-AT nano-conjugate showed solubility enhancement of nearly 4-fold and 100-fold compared to CH-AT conjugate and pure AT, respectively. In vitro drug release studies in simulated gastric fluid and simulated intestinal fluid suggested sustained release of AT from the conjugate. Additionally, the nano-conjugate significantly reduced the acidic degradation of AT. The plasma-concentration time profile of AT after oral administration of CH-AT nano-conjugate (2574±95.4 ng/mL) to rat exhibited nearly 5-fold increase in bioavailability compared with AT suspension (583±55.5 ng/mL). Finally, variable bioavailability, as observed for AT suspension was also reduced when AT was administered in form of CH-AT nano-conjugate. Taken together these data demonstrate that chitosan conjugate nano-prodrugs may be used as sustained polymeric prodrugs for enhancing bioavailability.

Nanometric gold in cancer nanotechnology: current status and future prospect

This review elaborate on modified gold nanoparticulate concept in oncology, provides an overview of the use of gold nanoparticles in cancer treatment and discusses their potential applications and clinical benefits.

Development and evaluation of nanosized niosomal dispersion for oral delivery of Ganciclovir

Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the oral absorption and prolong the existence of the drug in the systemic circulation. So the purpose of the present study was to improve the oral bioavailability of Ganciclovir by preparing nanosized niosomal dispersion. Niosomes were prepared from Span40, Span60, and Cholesterol in the molar ratio of 1:1, 2:1, 3:1, and 3:2 using reverse evaporation method. The developed niosomal dispersions were characterized for entrapment efficiency, size, shape, in vitro drug release, release kinetic study, and in vivo performance. Optimized formulation (NG8; Span60:Cholesterol 3:2 molar ratio) has shown a significantly high encapsulation of Ganciclovir (89u2009±u20092.13%) with vesicle size of 144u2009±u20093.47u2009nm (polydispersity index [PDI]u2009=u20090.08). The in vitro release study signifies sustained release profile of niosomal dispersions. Release profile of prepared formulations have shown that more than 85.2u2009±u20090.015% drug was released in 24u2009h with zero-order release kinetics. The results obtained also revealed that the types of surfactant and Cholesterol content ratio altered the entrapment efficiency, size, and drug release rate from niosomes. In vivo study on rats reveals five-time increment in bioavailability of Ganciclovir after oral administration of optimized formulation (NG8) as compared with tablet. The effective drug concentration (>0.69 µg/mL in plasma) was also maintained for at least 8u2009h on administration of the niosomal formulation. In conclusion, niosomes can be proposed as a potential oral delivery system for the effective delivery of Ganciclovir.

Enhanced antimalarial activity of lumefantrine nanopowder prepared by wet-milling DYNO MILL technique

Lumefantrine (LMF) is an antimalarial drug that exhibits poor oral bioavailability, owing to its poor aqueous solubility. To improve its antimalarial activity, nanopowder formulation using DYNO MILL was prepared. Combination of HPMC E3 (4%, w/v) and Tween 80 (2.5%, w/v) as dispersing agents, favored the production of smaller LMF particles with mean size of 0.251 μm. LMF nanopowder showed enhanced dissolution rate attributed to nanonization of LMF. The IC(50) value of nano-sized LMF was found to be 0.1 ng/mL, which was 175-times lower than the IC(50) value of unmilled LMF powder (17.5 ng/mL) and 42-times lower than the IC(50) value of chloroquine (4.2 ng/mL). The in vivo antimalarial activity demonstrated an enhanced antimalarial potential of LMF nanopowder against P. Yoelii nigeriensis compared to unmilled drug. Wet-milling using DYNO MILL offers a highly effective approach to produce stable drug nanopowders. Furthermore, LMF nanopowder makes the Coartem therapy more effective.

Assam Bora Rice Starch Based Biocompatible Mucoadhesive Microsphere for Targeted Delivery of 5-Fluorouracil in Colorectal Cancer

The aim of this study was to develop novel colon targeted mucoadhesive microspheres (MAMs) for site specific delivery of 5-fluorouracil (5-FU) to colon without the drug being released in the stomach or small intestine. MAMs were prepared using Assam Bora rice starch, a natural mucoadhesive polymer, by a double emulsion solvent evaporation method. The microspheres were characterized for their shape, size, surface morphology, size distribution, incorporation efficiency, and in vitro and in vivo drug release studies. The release study confirmed the insignificant release of 5-FU in physiological condition of stomach and small intestine and major drug release in the cecal content. In vivo release study of the optimized MAMs was compared with immediate release (IR) 5-FU. 5-FU was distributed predominantly in the upper GI tract from the IR, whereas 5-FU was distributed primarily to the lower part of the GI tract from the MAM formulation. Enhanced levels of liver enzymes were found in animals given IR 5-FU as well as augmented levels of serum albumin, creatinine, leucocytopenia and thrombocytopenia was also observed. Thus to sum up, it can be appropriately established that the 5-FU release pattern from MAMs exhibits slow and extended release over longer periods of time with reduced systemic side effects.

Dorzolamide-loaded PLGA/vitamin E TPGS nanoparticles for glaucoma therapy: Pharmacoscintigraphy study and evaluation of extended ocular hypotensive effect in rabbits.

Poor drug penetration and rapid clearance after topical instillation of a drug formulation into the eyes are the major causes for the lower ocular bioavailability from conventional eye drops. Along with this, poor encapsulation efficiency of hydrophilic drug in polymeric nanoparticles remains a major formulation challenge. Taking this perspective into consideration, dorzolamide (DZ)-loaded PLGA nanoparticles were developed employing two different emulsifiers (PVA and vitamin E TPGS) and the effects of various formulation and process variables on particle size and encapsulation efficiency were assessed. Nanoparticles emulsified with vitamin E TPGS (DZ-T-NPs) were found to possess enhanced drug encapsulation (59.8±6.1%) as compared to those developed with PVA as emulsifier (DZ-P-NPs). Transcorneal permeation study revealed a significant enhancement in permeation (1.8-2.5 fold) as compared to solution. In addition, ex vivo biodistribution study showed a higher concentration of drug in the aqueous humour (1.5-2.3 fold). Histological and IR-camera studies proved the non-irritant potential of the formulations. Pharmacoscintigraphic studies revealed the reduced corneal clearance, as well as naso-lachrymal drainage in comparison to drug solution. Furthermore, efficacy study revealed that DZ-P-NPs and DZ-T-NPs significantly reduced the intraocular pressure by 22.81% and 29.12%, respectively, after a single topical instillation into the eye.

Experimental investigation and oral bioavailability enhancement of nano-sized curcumin by using supercritical anti-solvent process.

The biomedical applications of curcumin (CUR) are limited due to its poor oral bioavailability. In this work, CUR nanoparticles were successfully prepared by combining the supercritical anti-solvent (SAS) process with Tween 80 as a solubilizing agent and permeation enhancer. Different processing parameters that can govern the mean particle size and size distribution of nanoparticles were well investigated by manipulating the types of solvents, mixing vessel pressure, mixing vessel temperature, CO2 flow rate, solution flow rate and solution concentration. Solid state characterization was done by Fourier Transform infrared spectroscopy, differential scanning calorimetry, dynamic light scattering, scanning electron microscopy, and powder X-ray diffraction study. Solubility and dissolution profile of SAS-processed CUR were found to be significantly increased in comparison with native CUR. Further, a validated ultra-performance liquid chromatographic method with quadrupole-time of flight-mass spectrometry was developed to investigate the pharmacokinetic parameters after a single oral dose (100mg/kg) administration of CUR (before/after SAS-processed) in male Wistar rats. From the plasma concentration vs. time profile graph, oral bioavailability of SAS-processed CUR was found to be increased approximately 11.6-fold (p<0.001) as compared to native CUR.

VALIDATED STABILITY INDICATING RP-HPLC METHOD FOR THE ESTIMATION OF LINEZOLID IN A PHARMACEUTICAL DOSAGE FORM

A rapid high performance liquid chromatographic method was developed and validated for the determination and stability evaluation of linezolid in pharmaceutical dosage forms. Separation of linezolid was successfully achieved on a C-18 column utilizing water: methanol (50:50 v/v) at a flow rate of 1 mL/min and eluate was monitored at 254 nm, with a retention time of 5.117 minute. The method was validated and the response was found to be linear in the drug concentration range of 0.001 mg/mL to 3.4 mg/mL. The mean values ± RSD of the slope and the correlation coefficient were found to be 51169 ± 0.290 and 0.9999, respectively. The RSD values for intra- and inter-day precision were found to be 0.782 (<1.00%) and 0.610 (<0.90%), respectively. The forced degradation kinetic study of linezolid by using HCl (0.5 N), NaOH (0.02 M), H2O2 (6%v/v), thermal (80 ± 2°C), and UV radiation (365 nm) were observed to be very specific.

Synthesis and in vitro localization study of curcumin-loaded SPIONs in a micro capillary for simulating a targeted drug delivery system

Nano-sized curcumin-loaded super-paramagnetic iron oxide nanoparticles (CUR-OA-SPIONs) were synthesized chemically by co-precipitation method using oleic acid as a stabilizer and Myrj 52 as a surfactant. The synthesized nanoparticles were characterized for their shape, size, surface morphology, electrokinetic potential, magnetic properties, crystalinity, chemical interactions and thermal transitions. The synthesized CUR-OA-SPIONs were spherical, mono-dispersed, physically stable and super-paramagnetic in nature. In vitro localization study and aggregation dynamics of CUR-OA-SPIONs were studied with a flow of blood inside a square glass capillary (500×500 μm(2) cross section) in the presence of an externally applied magnetic field (Ms=1200 mT). This research which is first of its kind showed the fluorescent imaging of CUR-OA-SPIONs with respect to time to understand the aggregation dynamics of magnetic nanoparticles in a micro capillary simulating the case of targeted drug delivery system. The size of the aggregation increases with respect to time (t=0(+)s to t=500 s), while no significant change in the size of the aggregate was observed after time t=500 s.