Jerry Nesamony

Calcium Alginate Nanoparticles Synthesized Through a Novel Interfacial Cross-Linking Method as a Potential Protein Drug Delivery System

The goal of this research work was to develop a novel technique to synthesize calcium alginate nanoparticles using pharmaceutically relevant microemulsions. Stable microemulsion-based reactors were prepared using aqueous sodium alginate, aqueous calcium chloride, dioctyl sodium sulfosuccinate (DOSS), and isopropyl myristate. The reactor microemulsions were characterized via conductivity and dynamic light scattering (DLS) experiments. The conductivity data indicated composition- and reagent-dependent variations in electrical conductivity when the aqueous phase containing reagents were present at or above a Wo (Wo = [DOSS]/[water]) value of 14. The reactor microemulsions were of approximately 6 nm sized droplets. When the reactor microemulsions were mixed and sonicated for 1 h approximately, 350-nm-sized calcium alginate nanoparticles were produced, as indicated by DLS measurements. The particles were isolated and characterized via low-vacuum scanning electron microscopy. The electron micrographs corroborate the DLS results. The nanoparticles were evaluated as a drug delivery system by incorporating bovine serum albumin (BSA) and performing in vitro release and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) studies. The BSA release profile was characterized by an initial burst release followed by a sustained-release phase. SDS-PAGE studies indicated that the incorporated protein did not suffer covalent aggregation or degradation via fragmentation.

Nebulized oil-in-water nanoemulsion mists for pulmonary delivery: development, physico-chemical characterization and in vitro evaluation

Abstract Context: This study presents novel nanostructured oil-in-water (o/w) mists based on self-nanoemulsifying (SNE) mixtures capable of delivering poorly water-soluble drugs into the lungs. Objective: Formulation development of an o/w nanoemulsion (NE) capable of being nebulized for pulmonary delivery of poorly water-soluble drugs. Materials and methods: SNE mixtures were prepared and evaluated using Tween 80 and Cremophor RH 40 as surfactants; Transcutol P, Capryol 90 and PEG 400 as cosurfactants; and Labrafac Lipophile Wl 1349 (a medium-chain triglyceride) as an oil. Liquid NEs were analyzed by light scattering, zeta potential, transmission electron microscopy (TEM) and in vitro drug release studies. The aqueous NE was nebulized and assessed by light scattering and TEM. The formulation was aseptically filtered and the sterility validated. In vitro cytotoxicity of the formulations was tested in NIH 3T3 cells. The capability of the formulation to deliver a poorly water-soluble drug was determined using ibuprofen. Results: Ibuprofen was found to be stable in the NEs. The formulations were neutrally charged with a droplet size of about 20 nm. TEM images displayed 100 nm oil droplets. The aseptic filtration method produced sterile NE. The nebulized mist revealed properties ideal for pulmonary delivery. The biocompatible aerosol has a nanostructure consisting of several oil nanodroplets enclosed within each water drop. Solubility and in vitro drug release studies showed successful incorporation and release of ibuprofen. Conclusion: The developed formulation could be used as an inhalation for delivering material possessing poor water solubility into the lungs.

Physico-chemical characterisation, cytotoxic activity, and biocompatibility studies of tamoxifen-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification method

Abstract Context: Solid lipid nanoparticles (SLNs) can efficiently and efficaciously incorporate anti-cancer agents. Objective: To prepare and characterise tamoxifen (TAM)-loaded SLNs. Materials and methods: Glyceryl monostearate, Tween-80, and trehalose were used in SLNs. SLNs were tested via dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Results: Characterisation studies revealed SLNs of about 540 nm with a negative surface charge and confirmed the entrapment of TAM in the SLNs. The entrapment efficiency was estimated to be 60%. Discussion: The in vitro drug release profile demonstrated a gradual increase followed by a release plateau for several days. A drug concentration-dependent increase in cytotoxic activity was observed when the SLNs were evaluated in cell cultures. Conclusion: Biocompatible and stable lyophilised SLNs were successfully prepared and found to possess properties that may be utilised in an anti-cancer drug delivery system.

Preparation, characterization, sterility validation, and in vitro cell toxicity studies of microemulsions possessing potential parenteral applications

Context: Water-in-oil microemulsions (w/o ME) are ideal for parenteral drug delivery. However, no such formulations have been tested for biocompatibility in in vitro cell cultures. Furthermore, sterilization of w/o MEs is a challenging process that has not been previously developed and validated. Purpose: To formulate pharmaceutically relevant water-in-oil (w/o) microemulsion’s systems suitable for use as a parenteral formulation. Methods: w/o MEs were prepared using dioctyl sodium sulfosuccinate (DOSS), ethyl oleate (EO), and water. Formulations were characterized using polarized light microscopy, electrical conductivity, rheology, and dynamic light scattering. An aseptic filtration method for sterilization was developed using membrane filtration. The biocompatibility of selected MEs were evaluated in NIH3T3 cell cultures. Dissolution studies were performed on microemulsions containing methylene blue to evaluate the drug release profile. Results: The maximum amount of water incorporated in the formulations was 14% w/w. DOSS/EO/water microemulsions exhibited Newtonian flow. Particle sizes for these MEs were less than 30 nm in size. Formulations filtered aseptically were free of bacteria when gram-stained and visualized under a microscope. All MEs showed no toxicity to NIH 3T3 cells. Discussion: The absence of birefringence and low conductivity values indicated that the formulations were w/o microemulsions. The filtration method of sterilization was validated by the absence of microbial growth on blood agar plates over a 14-day period. In vitro dye release studies demonstrate sustained release of the model drug over a 72-h time period. Conclusion: Characteristics delineated in this study demonstrate the potential for these formulations to be used as parenteral preparations.

Thermoresponsive fluconazole gels for topical delivery: rheological and mechanical properties, in vitro drug release and anti-fungal efficacy.

Abstract The aim of this study was to develop thermosensitive gels using poloxamers for topical delivery of fluconazole (FLZ). Eight different formulations containing 1% FLZ in poloxamer and a particular co-solvent (propylene glycol (PG) or Transcutol-P) of various concentrations were prepared. The gels were characterized for transition temperatures, rheological and mechanical properties. FLZ permeability and antifungal effect of the gels were also evaluated. Except for one formulation, all gels exhibited thermosensitive property, i.e. transformed from Newtonian (liquid-like) behavior at 20 °C to non-Newtonian (gel-like) behavior at 37 °C. Transcutol-P increased the transition temperature of the formulations, while the opposite effect was observed for PG. At 37 °C, formulations with high poloxamer concentrations (17%) resulted in high viscosity, compressibility and hardness. Formulations containing 17% poloxamer and 20% Transcutol-P and 10% PG, respectively, exhibited high adhesiveness. No significant differences in the in vitro antifungal activity of FLZ were observed among the formulations suggesting that the gel vehicles did not influence the biological effect of FLZ. FLZ permeability decreased with increasing poloxamer concentration. Formulations containing 17% poloxamer and 20% Transcutol-P and 10% PG seemed to be promising in situ gelling systems for the topical delivery of FLZ.

Smart Polymers in Drug Delivery

Smart polymers or stimuli-responsive polymers typically change their physical properties and/or structure in response to relatively minor changes in the stimulus. Changes in the environment that affect polymer properties can be called as the stimuli, while the resulting changes in the polymer and the system (such as dissolved state of the polymer in a solvent) has been termed as the response. The changes in the environment that have been exploited for biopharmaceutical applications are exemplified by pH, ionic strength, temperature, light,and magnetic or electric field. This chapter will highlight most popular smart polymers used in drug delivery.

A New Computational Decision Support System for Material Selection and Real-Time Monitoring and Evaluation of Aseptic Technique when Compounding Sterile Preparations

PurposeThe purpose of this project was to design a computational decision support system (DSS) for compounded sterile preparations (CSP).MethodsError-free compounding is dependent on the proper selection of components and adherence to procedure during compounding. A material selection system (MSS) based on a graphical user interface (GUI), coupled with a barcode scanner and back-end database, was developed and tested for proper selection of items involving three different medication orders (MO). A video processing system (VPS) was implemented in MATLAB that evaluated live video feed from the compounding hood to monitor the compounding procedure when compounding the MO’s. Surf detection was used to detect and locate compounding items placed in the hood. Various algorithms were developed and tested to enhance the accuracy and robustness of the VPS.ResultsThe MSS was tested for all items used in compounding the MO’s, and it performed error-free. The VPS evolved to VPS.03 from VPS.01 and VPS.02. The greatest accuracy and ability for real-time realization were seen in VPS.03. All deliberate mistakes made when compounding the tested medication orders were captured by VPS.03.ConclusionThe new computational decision support system facilitated error-free selection of components and was able to monitor and evaluate the compounding process in real time. The platform may be used in CSP compounding rooms, to audit techniques and procedures, and in training or educational settings.

Solid Lipid Nanoparticles in Drug Delivery: Opportunities and Challenges

Abstract Since their introduction in the early 1990s, solid lipid nanoparticles (SLNs) have received tremendous attention in drug delivery because of their ability to carry and solubilize lipophilic drugs and their small particle size, resulting in increased cellular uptake and absorption. SLNs are composed of physiological lipids, which reduce the risk of acute and chronic toxicity. However, SLNs are prone to instabilities because of their complex crystallization behavior due to the occurrence of polymorphic transitions. This chapter summarizes various aspects of SLNs such as components and production of SLNs, drug loading, drug release, stability, and application of SLNs in drug delivery. This chapter also provides a summary of SLNs as a potential carrier of anticancer drugs, one of the most aggressively expanding areas of research. A special emphasis is placed on the stability and toxicity issues associated with SLNs and their diagnostic applications.Since their introduction in the early 1990s, solid lipid nanoparticles (SLNs) have received tremendous attention in drug delivery because of their ability to carry and solubilize lipophilic drugs and their small particle size, resulting in increased cellular uptake and absorption. SLNs are composed of physiological lipids, which reduce the risk of acute and chronic toxicity. However, SLNs are prone to instabilities because of their complex crystallization behavior due to the occurrence of polymorphic transitions. This chapter summarizes various aspects of SLNs such as components and production of SLNs, drug loading, drug release, stability, and application of SLNs in drug delivery. This chapter also provides a summary of SLNs as a potential carrier of anticancer drugs, one of the most aggressively expanding areas of research. A special emphasis is placed on the stability and toxicity issues associated with SLNs and their diagnostic applications.