Search

Nanostructured lipid carriers (NLC) comprising soy lecithin (SLC), tristearin (TS) and palmitic acid (PA) having molar ratio 2:2:1 was modified by partially replacing SLC with ion pair amphiphile (NLCIPA), prepared by mixing equimolar aqueous solution of sodium dodecyl sulphate and hexadecyltrimethylammonium bromide. Hot homogenization followed by ultrasonication method was employed for the preparation of NLC and NLCIPA. Desirable SLC / IPA ratio for NLCIPA formulations were obtained by analyzing the interfacial behavior of the lipidic components in the presence of IPA at air-water interface. Considering the interfacial behavior and mutual miscibility, lipid compositions having SLC/IPA ratio equal to 2:3, 3:7 and 1:4 were selected for the preparation of NLCIPA. Analytical techniques like dynamic light scattering, differential scanning calorimetry, transmission electron microscopy, fridge fractured electron microscopy and atomic force electron microscopy assured higher stability of NLCIPA formulations compared to the conventional NLC and the NLCIPA with 30 mol% SLC was found to be optimum. Experimental evaluation of interfacial, solution phase and thermal characteristics of oleanolic acid (OA) loaded NLC and NLCIPA formulations indicated the accumulation of OA on the palisade layer and the drug acquisition was higher in NLCIPA than the conventional NLC. NLCIPA formulations were found even more promising to sustain the release of OA to a desirable extent. Higher cytotoxic activity for the OA loaded NLCIPA than the NLC was noted during the cytotoxicity studies on hepatocellular carcinoma, hepatocyte-derived carcinoma and colorectal carcinoma cancer cell lines. The NLCIPA formulations, therefore, can be considered as promising alternate to conventional NLC in improving the therapeutic efficacy of OA as the anticancer drug.

Effect of different surfactants (nonionic, anionic, cationic and zwitterionic) as stabilizer on the physicochemical properties of the nanostructured lipid carriers (NLC) comprising cetyl palmitate, triolein and palmitic acid were explored in the absence and presence of a potent antifungal drug, itraconazole. The blank and drug loaded NLC formulations were prepared by way of hot homogenization and ultrasonication technique. Combined dynamic light scattering, electron microscopy, atomic force microscopy, differential scanning calorimetry, UV–vis absorption spectroscopy and method of dialysis were adopted in characterizing the formulations. NLCs were stable up to 100 days irrespective of the surfactant. While the ionic surfactant comprising NLCs were electrostatically stable, the nonionic surfactants imparted better steric stabilization as revealed from the decreased size and polydispersity index values. Up shift in the phase transition temperature, changes in enthalpy and heat capacity in case of nonionic surfactant comprising systems substantiated its superior stabilization effect over the ionic surfactants. NLC formulations, stabilized by nonionic surfactants, exhibited superior drug incorporation, loading capacity and sustained release for itraconazole. Itraconazole loaded NLC formulations exhibited substantial antifungal activity against the fungal strain Aspergillusniger MTCC 3323. Such a comprehensive set of studies could assess the NLC formulation as potential drug delivery system for itraconazole.

Cystine-based gemini surfactants with dodecyl, tetradecyl, hexadecyl, and octadecyl hydrocarbon chains were synthesized, and their interactions with unsaturated (soy phosphatidylcholine, SPC)/saturated (hydrogenated SPC, HSPC) soy phosphatidylcholines in the forms of a monolayer and a model liposome were estimated for different combinations of the components in the mixed systems. Studies of Langmuir monolayers at the air-aqueous buffer interface revealed condensation of the monomolecular films with the addition of surfactants. The effect of surfactants decreased according to the following order: octadecylhexadecyltetradecyldodecyl homologs. The nonideal mixing between the components was estimated using the deviation of the experimental molecular area from the ideal area per molecule. The excess molecular area increased with the increase in the surfactant chain length and phospholipid saturation. The 50 mol % mixture of cystine derivatives and phospholipids formed thermodynamically stable monolayers. The surfactants increased the rigidity of SPC monolayers and decreased that of HSPC monolayers, as observed by the studies of surface dialational rheology. The film structure at the air-water interface could differentiate the SPC- and HSPC-comprising systems through the formation of organized regions, especially at a higher surface pressure. The constriction of surfactant/phospholipid hybrid vesicles was observed with an increase in the length of surfactant hydrocarbon chains. The negative zeta potential of vesicles took the highest values and did not change with time for 20 and 50 mol % surfactant. The spherical shape of the vesicles was confirmed by transmission electron microscopy. Differential scanning calorimetry revealed an increase in fluidity of HSPC bilayers and rigidity of SPS bilayers under the influence of surfactants. These effects were confirmed by fluorescence spectroscopy. All of the vesicle formulations were found to be nontoxic from the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay, suggesting their potential as a novel membranous system for the delivery of drugs, genetic materials, vaccines, and other therapeutic agents.

The impact of saturation and unsaturation in the fatty acyl hydrocarbon chain on the physicochemical properties of nanostructured lipid carriers (NLCs) was investigated to develop novel delivery systems loaded with an anticancer drug, ursolic acid (UA). Aqueous NLC dispersions were prepared by a high-pressure homogenization-ultrasonication technique with Tween 80 as a stabilizer. Mutual miscibility of the components at the air-water interface was assessed by surface pressure-area measurements, where attractive interactions were recorded between the lipid mixtures and UA, irrespective of the extent of saturation or unsaturation in fatty acyl chains. NLCs were characterized by combined dynamic light scattering, transmission electron microscopy (TEM), atomic force microscopy (AFM), differential scanning calorimetry, drug encapsulation efficiency, drug payload, in vitro drug release, and in vitro cytotoxicity studies. The saturated lipid-based NLCs were larger than unsaturated lipids. TEM and AFM images revealed the spherical and smooth surface morphology of NLCs. The encapsulation efficiency and drug payload were higher for unsaturated lipid blends. In vitro release studies indicate that the nature of the lipid matrix affects both the rate and release pattern. All UA-loaded formulations exhibited superior anticancer activity compared to that of free UA against human leukemic cell line K562 and melanoma cell line B16.

Nano-structured magnesium oxide was prepared by calcining its hydromagnesite phase, obtained by simple precipitation using magnesium acetate and ammonium carbonate under ambient condition. This MgO was used as active and reusable catalyst for the Knoevenagel condensation of aromatic aldehydes with malononitrile and ethylcyanoacetate under solvent-free conditions at room temperature. It also exhibits strong activity in solvent-free base catalyzed Claisen-Schmidt condensation of various substituted benzaldehydes with acetophenone. The basic sites of different strengths like surface hydroxyl groups, and low coordination O2− sites may be responsible for the above catalytic activity. The experimental results showed that the nano-MgO has high catalytic activity and can be recycled without significant loss of its activity.

Hybrid vesicles, prepared from soy phosphatidylcholine (SPC), ion pair amphiphile (IPA), cholesterol (CHOL) and dihexadecyldimethylammmonium bromide (DHDAB), were investigated to assess their potential as novel drug delivery systems for indomethacin (IMC), a nonsteroidal anti inflammatory drug (NSAID). The size, polydispersity index and zeta potential values of the vesicles were monitored with respect to time using dynamic light scattering (DLS) measurements which confirmed the profound effect of both DHDAB and the drug. Incorporation of DHDAB, although resulting in the size enhancement of the liposome, however, enhanced vesicle stability induced by electrostatic repulsion. Both conventional and freeze-fractured transmission electron microscopic (TEM) studies revealed the spherical morphology of the vesicles. FTIR studies confirmed perceptible interaction among the drug and the lipid–surfactant mixtures. Thermal behavior of the vesicles was assessed by means of differential scanning calorimetric (DSC) studies in order to understand the interaction between the incorporated NSAID and lipids. The state of polarity of IMC and another fluorescent molecular probe (7-hydroxycoumarin) were examined via absorption and emission spectroscopy respectively. Results on the fluorescence anisotropy studies helped in understanding the head group packing of the amphiphiles in the vesicles. An in vitro release study of the NSAID from vesicles revealed that incorporation of DHDAB promoted the release of the drug. Among different proposed models, the Korsmeyer–Peppas model was found to be the best one and the release mechanism was predominantly Fickian diffusion. The formulations, in the absence and presence of IMC showed no cytotoxicity in healthy human blood cell lymphocyte as well as in the human breast adenocarcinoma cell line (MCF 7). The aforementioned studies provided deeper insight into the interaction pattern of DHDAB with hybrid vesicles thereby exploring the usefulness of such systems as effective drug carriers.

Orcinol glucoside (OG) - loaded nanostructured lipid carrier (NLC), coated with polyethylene glycol-25/55-stearate (PEG-25/55-SA), were explored for delivering OG to improve in vitro cytotoxicity against gastrointestinal tract (GIT), colon and hepatoma carcinoma cell lines. It is being expected that the PEGylated formulations would possess the sustainability in withstanding the adverse physiological extremities like the most significant metabolic activities and phase I / II enzymatic activities in the intestines. NLCs were prepared using tristearin, oleic acid and PEG-25/55-stearate by hot homogenization-ultrasonic dispersion; characterized by DLS, TEM, SEM, AFM, entrapment efficiency and drug loading capacity studies. NLC diameter ranged from 160 to 230 nm with negative zeta potential of −8 to −20 mV. TEM/SEM and AFM studies suggest spherical and smooth surface morphologies. Differential scanning calorimetry studies reveal the loss of crystallinity when OG was incorporated into the NLC. NLCs showed initial burst release, followed by sustained release of OG. PEG-NLC exhibited superior anticancer activity against GIT and also in hepatoma cancer cell lines. This is the first report demonstrating a practical approach for possible oral delivery of OG in GIT and targeting hepatoma cancer, warranting further in vivo studies for superior management of GIT cancer.

Hydrogenated soy phosphatidylcholine, tristearin and oleic acid were employed in preparing nanostructured lipid carriers (NLC). Surface modified NLCs ( $$\hbox {NLC}_\mathrm{PEG})$$ were formulated by adding polyethylene glycol 2000 (PEG 2000) in the dispersion medium along with Tween 60. Hot homogenization followed by ultrasonication technique was used as the preparative procedure. 0.01% (w/v, g/mL) PEG 2000 was found to be the saturation limit for the studied formulations. Pyrazinamide (PYZ) was incorporated in NLC; the base and drug-loaded formulations were characterized by combined dynamic light scattering (DLS), differential scanning calorimetry (DSC), transmission electron microscopy (TEM) and atomic force microscopy (AFM). $$\hbox {NLC}_\mathrm{PEG}$$ was more stable than the conventional NLC formulations. Added PEG 2000 provided extra steric stability to $$\hbox {NLC}_\mathrm{PEG}$$ systems by introducing an additional layer over their surface. The presence of the additional layer of PEG 2000 also offered a preventative barrier towards the expulsion of surface accumulated PYZ. Considerable improvement in entrapment efficiency (EE%), drug loading (DL%) and desirable sustained release profile could be achieved in NLC. Nanostructure lipid carrier (NLC) formulations were modified with PEG 2000. Pyrazinamide (PYZ) was incorporated into the NLC. Stability, entrapment efficiency and drug loading of the $$\hbox {NLC}_\mathrm{PEG}$$ formulations were better than NLC. Sustained release of incorporated PYZ was recorded for $$\hbox {NLC}_\mathrm{PEG}$$ .

Nanostructured lipid carriers (NLCs), with potential drug delivery capabilities, were formulated using soy lecithin (SLC), tristearin (TS) and palmitic acid (PA) in the absence and presence of two anti-inflammatory drugs, diclofenac sodium (DNa) and indomethacin (IMC). Tween 60 was used as a stabilizer separately and in combination with sodium carboxymethyl cellulose (NaCMC, anionic), polyethylene glycol (PEG, nonionic) and an N,N-dimethyl-N-dodecyl derivative of hydroxyethyl cellulose (LM200, cationic). Both DNa and IMC substantially decreased the size and increased the polydispersity index (PDI) of the NLCs. The hydrodynamic parameters, viz., size, zeta potential, and polydispersity index, as well as the thermal behaviour of the NLCs, depended on the type and charge of the added polymers. Weak interactions between the drug and lipid matrices in the bulk mixtures were confirmed through FT-IR studies. The NLC formulations exhibited lower entrapment efficiency and loading content in the case of DNa compared to IMC due to the higher ionic nature of the former drug. The polymers influenced the entrapment efficiency and loading ability of the NLCs in case of both DNa and IMC. 85% of the entrapped DNa was released from the NLC, compared to 54% release in the case of IMC; the drug release rates were higher for the PEG and NaCMC coated systems. LM200 delayed the drug release process with respect to NaCMC and PEG. Both DNa- and IMC-loaded NLCs inhibited the growth of Gram-positive bacteria, Bacillus amyloliquefaciens. It was concluded that the physicochemical properties of NLCs could effectively be modified using polymers; thus, the biomimetic characteristics of lipids and architectural advantage of polymers can be combined to yield a superior drug delivery system.

This study aimed to investigate the effect of hydrocarbon chain length of nonionic surfactants, Tween 40 and Tween 60, on the physicochemical properties of nanostructured lipid carriers (NLCs). Two local anaesthetics, lidocaine (LIDO) and procaine hydrochloride (PRO·HCl), were incorporated in the NLCs. NLC formulations were prepared using sorbitantristearate (Span 65), soy lecithin (SLC) and stearic acid (SA) in a 2 : 2 : 1 mole ratio employing the hot homogenization technique. The systems were characterized by combined dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and spectroscopic studies. The formulations were found to be stable up to 60 days when kept at 4 °C. NLCs stabilized by Tween 60 were superior to the corresponding Tween 40 based formulations. A spherical morphology with smooth surfaces was evidenced by TEM measurements. DSC and polarity studies indicated that LIDO altered the crystallinity of the lipid matrices as it could insert into the core of the NLC. Entrapment efficiency (EE) and loading content (LC) studies revealed that Tween 60 stabilized NLCs have better drug loading capability than the Tween 40 based formulation. Controlled and prolonged drug release was experienced by Tween 60 stabilized drug loaded NLCs as studied by in vitro release kinetics. The developed NLCs could thus be considered to have prospects as novel drug carriers for controlled/sustained release to improve the time duration of anaesthesia, especially for topical application.

The physicochemical properties of large unilamellar vesicles (LUVs) were assessed with respect to lipid composition, pH, time, and temperature by monitoring their size, zeta potential, drug payload, and thermal behavior. A conventional thin film hydration technique was employed to prepare liposomes from soy phosphatidylcholine (SPC), dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG), and a 7:3 (M/M) mixture of DPPC+DPPG along with 30 mole% cholesterol in each combination. While the size of liposomes depended on lipid composition, pH and temperature, the zeta potential was found to be independent of the pH of the medium, although it varied with liposome type. Spherical morphology and bilayer were observed by electron microscopy. The phase transition temperature increased with decreasing pH. Membrane micro-viscosity showed the highest value for SPC, and membrane rigidity increased with increasing pH. The entrapment efficiency of liposomes with reference to curcumin was as follows: DPPC>DPPC+DPPG>DPPG>SPC. Sustained release of curcumin was observed for all liposomes. Curcumin-loaded liposomes exhibited substantial antibacterial activity against the gram-positive bacteria Bacillus amyloliquefaciens. Additional studies are needed to improve the understanding of the effect of formulation variables on the physicochemical stability of liposomes.

Synthesis of various industrially important fine chemicals under microwave irradiation (MWI) in solvent-free conditions over mesoporous zirconium phosphate (m-ZrP) is reported. m-ZrP is synthesized by MWI in basic medium using a precursor solution of zirconium carbonate complex as zirconium source and CTAB as a pore-directing agent. MWI time and MWI power were found to have significant influence on the textural properties of synthesized m-ZrP. Microscopic analyses of the synthesized m-ZrP indicate the presence of worm like pores with spherical morphology. DRIFT analysis of pyridine adsorbed m-ZrP and NH3-TPD measurements indicate the presence of appreciable amount of Bronsted acid sites. Synthesized m-ZrP exhibits high catalytic activity towards Claisen–Schmidt condensation reaction in solvent-free conditions under microwave irradiation. The m-ZrP showed high activity towards other acid catalyzed reactions such as Friedel–Craft benzylation, Pechmann condensation and carbonyl group protection reaction, and also for the synthesis of benzo-xanthenes in solvent-free conditions under MWI. The catalytic activity of m-ZrP is substantially higher than that of conventional layered ZrP. The synthesized catalysts are re-usable for at least five times after regeneration, without losing their catalytic activity significantly.

Mesoporous zirconium phosphate (m-ZrP) having high specific surface area and narrow pore size distributions is synthesized in basic medium using zirconium carbonate as source of zirconium. The concentration of phosphate in precursor solutions, as well as the calcination temperature, is found to influence the textural properties and acidity of synthesized m-ZrP significantly. Microscopic analysis indicates the presence of worm like pores with spherical morphology. The porous structure has remarkable thermal stability (up to 800 °C). DRIFT and NH3-TPD analysis suggest the presence of reasonable amount of Lewis and Bronsted acid sites. High catalytic activity of synthesized m-ZrP is observed towards Friedel–Craft (F.C.) benzylation reaction. The effect of acid strength of catalyst, reaction time, temperature and amount of catalyst towards Friedel–Craft benzylation reaction are also studied. The m-ZrP is highly active towards other acid catalyzed reactions in solvent-free conditions. The catalytic activity of m-ZrP is much higher than that of conventional layered ZrP. The catalysts were separated easily from reaction mixture, regenerated after a simple activation step and reused at least six times without significant loss in catalytic activity.

Ion-pair amphiphiles (IPAs) are neoteric pseudo-double-tailed compounds with potential as a novel substitute of phospholipid. IPA, synthesized by stoichiometric/equimolar mixing of aqueous solution of hexadecyltrimethylammonium bromide (HTMAB) and sodium dodecyl sulfate (SDS), was used as a potential substituent of naturally occurring phospholipid, soylecithin (SLC). Vesicles were prepared using SLC and IPA in different ratios along with cholesterol. The impact of IPA on SLC was examined by way of surface pressure (π)-area (A) measurements. Associated thermodynamic parameters were evaluated; interfacial miscibility between the components was found to depend on SLC/IPA ratio. Solution behavior of the bilayers, in the form of vesicles, was investigated by monitoring the hydrodynamic diameter, zeta potential, and polydispersity index over a period of 100 days. Size and morphology of the vesicles were also investigated by electron microscopic studies. Systems comprising 20 and 40 mol % IPA exhibited anomalous behavior. Thermal behavior of the vesicles, as scrutinized by differential scanning calorimetry, was correlated with the hydrocarbon chain as well as the headgroup packing. Entrapment efficiency (EE) of the vesicles toward the cationic dye methylene blue (MB) was also evaluated. Vesicles were smart enough to entrap the dye, and the efficiency was found to vary with IPA concentration. EE was found to be well above 80% for some stable dispersions. Such formulations thus could be considered to have potential as novel drug delivery systems.