Gourab Karmakar

Physicochemical studies on local anaesthetic loaded second generation nanolipid carriers

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.

Influence of Lipid Composition, pH, and Temperature on Physicochemical Properties of Liposomes with Curcumin as Model Drug

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.

Ion-pair amphiphile: a neoteric substitute that modulates the physicochemical properties of biomimetic membranes.

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.

Influence of Lipid Core Material on Physicochemical Characteristics of an Ursolic Acid-Loaded Nanostructured Lipid Carrier: An Attempt To Enhance Anticancer Activity

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.

Effect of polymer charge on the formation and stability of anti-inflammatory drug loaded nanostructured lipid carriers: physicochemical approach

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.

Effect of double tailed cationic surfactants on the physicochemical behavior of hybrid vesicles

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.

Effects of Fatty Acids on the Interfacial and Solution Behavior of Mixed Lipidic Aggregates Called Solid Lipid Nanoparticles

Mutual miscibility of soylecithin, tristearin, fatty acids (FAs), and curcumin was assessed by means of surface pressure-area isotherms at the air-solution interface in order to formulate modified solid lipid nanoparticles (SLN). Appearance of minima in the excess area (Aex) and changes in free energy of mixing (∆G(0)ex) were recorded for systems with 20 mole% FAs. Modified SLNs, promising as topical drug delivery systems, were formulated using the lipids in combination with curcumin, stabilized by an aqueous Tween 60 solution. Optimal formulations were assessed by judiciously varying the FA chain length and composition. Physicochemical properties of SLNs were studied such as the size, zeta potential (by dynamic light scattering), morphology (by freeze fracture transmission electron microscopy), and thermal behavior (by differential scanning calorimetry). The size and zeta potential of the formulations were in the range 300-500 nm and -10 to -20 mV, respectively. Absorption and emission spectroscopic analyses supported the dynamic light scattering and differential scanning calorimetry data and confirmed localization of curcumin to the palisade layer of SLNs. These nanoparticles showed a sustained release of incorporated curcumin. Curcumin-loaded SLNs were effective against a gram-positive bacterial species, Bacillus amyloliquefaciens. Our results on the physicochemical properties of curcumin-loaded SLNs, the sustained release, and on antibacterial activity suggest that SLNs are promising delivery agents for topical drugs.

Biophysical Correlates on the Composition, Functionality, and Structure of Dendrimer–Liposome Aggregates

Interaction between negatively charged liposomes and cationic polyamidoamine dendrimers of different generations was investigated through size, zeta potential, turbidity, electron microscopy, atomic force microscopy, fluorescence spectroscopy, and calorimetric studies. Liposomes with the binary combination of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) + dihexadecyl phosphate, DPPC + 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol, DPPC + 1,2-dipalmitoyl-sn-glycero-3-phosphate, and DPPC + 1,2-dipalmitoyl-sn-glycero-3-phosphoethanol were stable up to 60 days. The electrostatic nature of dendrimer–lipid bilayer interaction was evidenced through charge neutralization and subsequent reversal upon added dendrimer to liposome. Dendrimer–liposome interaction depended on its generation (5 > 4 > 3) in addition to the charge, head groups, and hydrocarbon chain length of lipids. Fluorescence anisotropy and differential scanning calorimetry studies suggest the fluidization of the bilayer, although the surface rigidity was enhanced by the added dendrimers. Thermodynamic parameters of the interaction processes were evaluated by isothermal titration and differential scanning calorimetric studies. The binding processes were exothermic in nature. The enthalpy of transition of the chain melting of lipids decreased systematically with increasing dendrimer concentration and generation. Dendrimer–liposome aggregates were nontoxic to healthy human blood cell, suggesting the potential of such aggregates as drug delivery systems.