Abhijeet P. Pandey

Polyethylenimine: A versatile, multifunctional non-viral vector for nucleic acid delivery.

Polyethylenimine (PEI) has recently been widely studied for the design of nucleic acid delivery vehicles. Gene delivery using PEI involves condensation of DNA into compact particles, uptake into the cells, release from the endosomal compartment into the cytoplasm, and uptake of the DNA into the nucleus. PEIs being positively charged, linear or branched polymers are able to form nanoscale complexes with small RNAs, leading to RNA protection, cellular delivery, and intracellular release. This review highlights the important properties of various PEIs with regard to their use for nucleic acid delivery. Brief discussion on cellular uptake mechanism of non-viral vector is included to understand its utility for gene delivery. Applications of modified PEI for increased efficacy, altered pharmacokinetic properties; improved biocompatibility and targeted delivery have also been discussed. An overview of simulation studies which can help in understanding the underlying complexation mechanism has also been included. The review provides a brief discussion about clinical trials and patents related to nucleic acid delivery using PEI based systems.

Graphene oxide based magnetic nanocomposites for efficient treatment of breast cancer

The present work reports a simple one step synthesis of nanoscale graphene oxide magnetic composites (GO-IO) using ferrofluid (GO-IOF). The obtained GO-IO were compared with GO-IO obtained from in situ (GO-IOI) methods. Anastrozole (ANS) was loaded on the GO-IOI and GO-IOF via simple stirring method to form GO-IOA and GO-IOFA respectively. These GO-IO prepared by two techniques were characterized using spectroscopic techniques and vibrating sample magnetometer (VSM) analysis. Particle size and potential were measured using Malvern Zetasizer. Scanning electron microscopy (SEM) was used for studying the surface morphology of GO-IO, and in addition to this elemental analysis was also performed for confirming the presence of iron. The cell viability assay was carried out using the MCF-7 cell line. It revealed that GO-IOFA had reasonably high cytotoxicity (49.7%) compared to GO (13.1%), ANS (16.6), GO-IOI (13%), GO-IOF (13.6) and GO-IOIA (18.34%). Both, GO-IOIA and GO-IOFA showed improved cytotoxicity when compared with pure ANS. GO-IOF were found to exhibit superior magnetic activity due to higher iron content along with smaller particle size and higher loading efficiency compared to GO-IOI. The overall effect suggests that GO-IO can be utilized as efficient carriers for the loading of chemotherapeutic agents.

Applying quality by design (QbD) concept for fabrication of chitosan coated nanoliposomes

Abstract In the present investigation, a quality by design (QbD) strategy was successfully applied to the fabrication of chitosan-coated nanoliposomes (CH-NLPs) encapsulating a hydrophilic drug. The effects of the processing variables on the particle size, encapsulation efficiency (%EE) and coating efficiency (%CE) of CH-NLPs (prepared using a modified ethanol injection method) were investigated. The concentrations of lipid, cholesterol, drug and chitosan; stirring speed, sonication time; organic:aqueous phase ratio; and temperature were identified as the key factors after risk analysis for conducting a screening design study. A separate study was designed to investigate the robustness of the predicted design space. The particle size, %EE and %CE of the optimized CH-NLPs were 111.3 nm, 33.4% and 35.2%, respectively. The observed responses were in accordance with the predicted response, which confirms the suitability and robustness of the design space for CH-NLP formulation. In conclusion, optimization of the selected key variables will help minimize the problems related to size, %EE and %CE that are generally encountered when scaling up processes for NLP formulations. The robustness of the design space will help minimize both intra-batch and inter-batch variations, which are quite common in the pharmaceutical industry.

Aripiprazole loaded poly(caprolactone) nanoparticles: Optimization and in vivo pharmacokinetics.

In the present investigation, a Quality by Design strategy was applied for formulation and optimization of aripiprazole (APZ) loaded PCL nanoparticles (APNPs) using nanoprecipitation method keeping entrapment efficiency (%EE) and particle size (PS) as critical quality attributes. Establishment of design space was done followed by analysis of its robustness and sensitivity. Characterization of optimized APNPs was done using DSC, FT-IR, PXRD and TEM studies and was evaluated for drug release, hemocompatibility and nasal toxicity. PS, zeta potential and %EE of optimized APNPs were found to be 199.2±5.65nm, -21.4±4.6mV and 69.2±2.34% respectively. In vitro release study showed 90±2.69% drug release after 8h. Nasal toxicity study indicated safety of developed formulation for intranasal administration. APNPs administered via intranasal route facilitated the brain distribution of APZ incorporated with the AUC0→8 in rat brain approximately 2 times higher than that of APNPs administered via intravenous route. Increase in Cmax was observed which might help in dose reduction along with reduction in dose related side effects. The results of the study indicate that intranasally administered APZ loaded PCL NPs can potentially transport APZ via nose to brain and can serve as a non-invasive alternative for the delivery of APZ to brain.

Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route.

Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors.

Sonication-assisted drug encapsulation in layer-by-layer self-assembled gelatin-poly (styrenesulfonate) polyelectrolyte nanocapsules: process optimization

Abstract We report the development of Layer-by-Layer (LbL) polyelectrolyte self-assembled nanocrystalline drug-delivery platform using two experimental factors, namely the number of coatings and temperature during deposition with three varying levels. The optimized formulation (Fopt) was assessed for zeta potential and particle size using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM). Charge reversal along with an increase in particle size confirmed coating of polyelectrolyte on drug nanocrystals. The FT-IR study revealed no signs of incompatibility or change in formulation property during preformulation and stability study. This fact was further supported by DSC results.

Magnetically responsive siliceous frustules for efficient chemotherapy

In the present investigation, curcumin loaded magnetically active frustules have been reported. The diatoms were cultured and frustules were obtained by chemical and thermal processes. The frustules were rendered magnetically active by incorporation of iron oxide nanoparticle using two different methods involving ferrofluid (CMDM-F) and in situ synthesis (CMDM-I) of iron oxide nanoparticle. These CMDM prepared by two techniques were characterized using FT-IR and vibrating sample magnetometer (VSM) analyses. Particle size and potential were measured using the Malvern Zetasizer. Scanning electron microscopy (SEM) was utilized for studying the surface morphology of CMDM, and in addition to this elemental analysis was also performed for confirming the presence of iron. The cell viability assay was carried out using the HeLa cell line. SEM images showed a change in surface morphology of diatoms before and after rendering magnetic activity. Cell viability assay revealed that CMDM-F had reasonably high cytotoxicity (60.2%) compared to Curcumin (42.1%), DM (1.9%), CDM (44.8%), and CMDM-I (59.9). Both, CMDM-F and CMDM-I showed improved cytotoxicity when compared with pure curcumin. The overall study suggests that the developed CMDM could be utilized as a potential carrier to deliver cargo for efficient chemotherapy.

Fabrication and characterization of graphene-based hybrid nanocomposite: assessment of antibacterial potential and biomedical application

Abstract The present investigation deals with synthesis of graphene oxide (GO) and fabrication of GO-based hybrid nanocomposites (Ncs). Synthesized GO and Ncs were primarily confirmed by UV visible and Fourier transform infrared (FT-IR) spectroscopy. Fabricated Ncs showed potential antimicrobial activity against Gram-positive and Gram-negative bacterial strains. Surface morphology, Elemental analysis, and FTIR imaging analysis were carried out to confirm Ncs formation. The Ncs were impregnated into the pullulan polymeric layer-by-layer (LbL) ultrathin film by using novel spin-coating approach. Mechanical properties were determined using Brookfield texture analyzer, and percentage moisture content confirmed the physicochemical stability of LbL film.

Optimization of desolvation process for fabrication of lactoferrin nanoparticles using quality by design approach

Abstract The present work deals with the design and process optimization for preparation of lactoferrin nanoparticles as carrier for delivery of curcumin (CLf-NPs) using quality by design (QbD) approach. Desolvation technique was selected for preparation of Lf-NPs. The concept of QbD was followed in stepwise manner including risk analysis FMEA methodology. Plackett–Burman screening design employing eight factors and two levels was selected for screening study and custom design was selected for further analysis. Curcumin was used as model polyphenol for assessing the encapsulating efficiency of Lf-NPs.

Fabrication and characterization of shape memory polymers based bioabsorbable biomedical drug eluting stent.

Abstract Present investigation deals with, tacrolimus eluting, self-expandable, biodegradable stent fabricated by solvent casting method. The design was based on shape memory polymers, which possess the ability to memorize temporary shape that can substantially differ from their initial permanent shape. A set of biodegradable polymers blend was used such as poly-lactic acid (PLA) and poly-l-glycolic acid (PLGA) to study the shape memory effect of polymer. The prepared stent was assessed for various parameters like Scanning Electron Microscopy (SEM), In-vitro and Ex vivo expansion, Drug content, In-vitro drug release, Haemocompatibility, Differential Scanning Calorimetry (DSC), Fourier Transform Infrared spectroscopy (FTIR), and Textural Characterization.