Pharmacosomes as Drug Delivery System: An Overview

Pharmacosomes are the colloidal dispersions of drugs covalently bound to lipids and can exist, depending on the chemical structure, as ultrafine vesicular, micellar, or hexagonal aggregates. Because of the linking of a drug (pharmakon) to a carrier (soma), they are rightly termed "pharmacosomes."Pharmacosomes can be characterized as a neutral molecule with both positive and negative charges, water-loving and fat-loving characteristics, and in complex form, an ideal polyphenol-to-phospholipid ratio. Pharmacosomes are amphiphilic lipid vesicular systems that have demonstrated their ability to increase the bio-accessibility of poorly water-soluble and poorly lipophilic medicines. Drug pharmacosomes provide an effective method of delivering the drug directly to the infection site, which contributes to a lowering in drug toxicity without harmful effects, and also lowers the cost of therapy by improving the drug's bioavailability, particularly in the case of poorly soluble drugs. Pharmacosomes are appropriate to incorporate both hydrophilic and lipophilic drugs. Pharmacosomes have been designed for multiple anti-inflammatory medications that are non-steroidal, neurological, and antineoplasty.

Phospholipids Uniquely Modify Secondary Structure of α-Synuclein Oligomers

ABSTRACTParkinson disease (PD) is a severe neurological disorder that affects more than a million people in the U.S. alone. A hallmark of PD is the formation of intracellular α-synuclein (α-Syn) protein aggregates called Lewy bodies (LBs). Although this protein does not have a particular localization in the central neural system, α-Syn aggregates are primarily found in certain areas of midbrain, hypothalamus and thalamus. Microscopic analysis of LBs revealed fragments of lipid-rich membranes, organelles and vesicles. These and other pieces of experimental evidence suggest α-Syn aggregation can be triggered by lipids. In this study, we used atomic force microscope Infrared (AFM-IR) spectroscopy to investigate structural organization of individual α-Syn oligomers grown in the presence of two different phospholipids vesicles. AFM-IR is a modern optical nanoscopy technique that has single-molecule sensitivity and sub-diffraction spatial resolution. Our results show that α-Syn oligomers grown in the presence of phosphatidylcholine have distinctly different structure than oligomers grown in the presence on phosphatidylserine. We infer that this occurs because of specific charges adopted by lipids, which in turn governs protein aggregation. We also found that protein to phospholipid ratio makes a substantial impact on the structure of α-Syn oligomers. These findings demonstrate that α-Syn is far more complex than expected from the perspective of structural organization of oligomeric species.

PREPARATION AND CHARACTERIZATION OF ETODOLAC BEARING EMULSOMES

Objective: Emulsomes are novel vesicular drug delivery system with an internal solid lipid core surrounded by one or more bilayers of phospholipids. Etodolac is a potent anti-inflammatory drug and is a drug of choice for the treatment of various diseases. The present study is focused on the development of emulsomes using etodolac as drug candidates having improved drug loading with sustained-release effect for patient compliance. Methods: Emulsomes formulation composed of solid lipids (tristearin), phospholipids, cholesterol, stearylamine, and drug (etodolac) were prepared by lipid film hydration method followed by sonication to produce emulsomes of the nanometric size range. All the formulations were optimized by using box-behnken design of experiment considering 3 factors viz. drug to phospholipid ratio (A), tristearin to phospholipid ratio (B), stearylamine to phospholipid ratio (C) at 3 levels lower (-1), middle (0) and upper (+1). The response of the independent variables (A, B, C) was studied on the dependent variable viz. particle size (Y1), zeta potential (Y2), and entrapment efficiency (Y3). The responses were analyzed by design expert software to find out the optimized values of variables within the design space. Results: Compatibility with excipients was established by FTIR studies. The developed emulsomes were spherical shape vesicles as analyzed by TEM. The optimized batch (OB) was evaluated for particle size, zeta potential, and entrapment efficiency with experimental values 383.1 ± 11.7 nm, 47.2 ± 1.3 mV and 80.1 ± 3.2% and predicted values 390.394 nm, 45.000 mV and 81.642 %, respectively. The experimental values were found in reasonable agreement with predicted values by the design of the experiment. In vitro drug release study showed sustained release of the drug (88.69 % after 24 h). Conclusion: Etodolac loaded emulsomes is a novel drug delivery system and found to reliable in terms of various characteristic parameters like particle size, zeta potential, entrapment efficiency, and drug release. 3-factors 3-levels Box-behnken design of the experiment is a suitable design for the optimization of emulsomes.

DRUGS CONTAINING GLYCYRRHIZIC ACID IN COMPLEX THERAPY FOR PULMONARY TUBERCULOSIS

The effectiveness of etiotropic chemotherapy is largely determined by the tolerability o the TB drugs (TBD) and the severity of unwanted side effects. It is known about the immunopathological effect of TBD, which can also be attributed to the undesirable effects of anti-tuberculosis chemotherapy. Changes in the structure and composition of mononuclear membranes reflect their functional activity. Secondary disorganization of the lipid bilayer due to the action of TBD is an important element in the development of immunosuppressive conditions in pulmonary tuberculosis and requires specific correction. The paper has the results of a survey of 308 patients with tuberculosis included. The comparison group consisted of 36 healthy volunteers. The membrane destruction coefficient and cholesterol-phospholipid ratio were used in order to assess the state of peripheral blood mononuclear cells and the degree of structural disorganization of their membranes. The prescription of preparations containing glycyrrhizic acid is pathogenetically substantiated and allows improving the state of the membranes of mononuclear cells, thereby reducing the undesirable membrane-toxic effect of first-line anti-tuberculosis drugs, There was an increase in etiotropic therapy intensity on the basis of abacilation at the end of the intensive phase of the main course of chemotherapy from 61% to 72.4% when using Licorice Root, and to 81.3% when using Fosfogliv® in patients with focal and infiltrative pulmonary tuberculosis.

Influence of platelet-activating factor, lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level

Three structurally related but differing in biological activities single-chained ether phospholipids (PAF (platelet-activating factor) and lyso-PAF) and an anti-cancer drug (edelfosine (ED)) were investigated in Langmuir monolayers imitating natural membranes. The aim of the undertaken experiments was to study the influence of these lipids on monolayers mimicking plasma membranes of cell lines differing in susceptibility to the anti-cancer activity of ED, i.e. promyelocytic leukaemia cells (HL-60) and promyeloblastic leukaemia cells (K-562). As these cells differ essentially in the cholesterol/phospholipid ratio and plasmalogen concentration in the membrane, we have carried out systematic investigations in artificial systems of various compositions. The results for model leukaemia cell membrane were compared with data acquired for systems imitating normal leucocytes. Our results show that the level of plasmalogens significantly modulates the influence of the single-chained phospholipids on the investigated systems. The experiments confirmed also that the interactions of ether lipids with a model membrane of HL-60 cells (in biological tests sensitive to ED) have opposite character when compared with K-562, being resistant to ED. Moreover, the values of the parameters characterizing monolayers serving as membrane models (strength of interactions, monolayers fluidity and morphology) proved both sensitivity of these cells to ED and lack of their susceptibility towards PAF. Interestingly, it has been found that lyso-PAF, which is usually described as an inactive precursor of PAF, displays a stronger effect on HL-60 model membranes than ED.

Anti-cholelithogenic effect of dietary tender cluster beans (Cyamopsis tetragonoloba) on the formation of cholesterol gallstones in mice

Providing a lithogenic diet that contains 0.5% cholesterol to experimental mice for 10 weeks resulted in cholesterol supersaturation in gallbladder bile, which induced the formation of cholesterol gallstones. In this study, to evaluate the anti-cholelithogenic potential of dietary tender cluster bean, a freeze-dried powder of the test legume was included in the lithogenic diet at 5%, 10%, and 15%. Dietary cluster beans reduced the cholesterol gallstone incidence by 43%, 46%, and 58% at the respective doses. Dietary cluster beans markedly reduced biliary cholesterol and, hence, the cholesterol saturation index. This was corroborated by the beneficial modification of the cholesterol/phospholipid ratio and the cholesterol/bile acid ratio in the bile. Dietary cluster beans countered the alterations in serum and liver cholesterol and lipid profiles caused by the lithogenic diet. Thus, dietary tender cluster beans exerted an anti-cholelithogenic influence by decreasing cholesterol hypersecretion into bile and, hence, the cholesterol saturation index, decreasing the formation of lithogenic bile in experimental mice.