INSIGHTS INTO THE SELF ASSEMBLED LIPID-POLYMER HYBRID NANOPARTICLES AS DRUG DELIVERY SYSTEM

SELF ASSEMBLED LIPID-POLYMER HYBRID NANOPARTICLES AS DRUG DELIVERY SYSTEM

Presented By:Rahul GuptaM .Pharmacy (1st year)Department of Pharmacy Barkatullah University Bhopal

contentsINTRODUCTIONADVANTAGESMETHOD OF PREPARATIONDRUG LOADING AND ENTRAPMENT EFFICIENCYPHYSICOCHEMICAL CHARACTERISTICSAPPLICATIONS IN DRUG DELIVERYCONCLUSIONREFERENCES

introductionLipid-Polymer Hybrid Nanoparticles are solid, submicron particles which composed of at least two components: the polymeric core and the lipid membrane.

This multilayered colloidal delivery vehicle which comprises of a core of natural hydrophilic polymer made up of cross-linked polysaccharide or a cross-linked oligosaccharide, the core is partially coated or completely coated with a layer which is either a lipid layer or an amphiphillic compound such as phosphplipid.

This particulate system have been introduced in an effort to mitigate some limitations associated with liposomes and polymeric nanoparticles.

The suitable examples of naturally cross-linked polysaccharides are cellulose and its derivatives including chemically cross-linked polysaccharides, for example, epichlorohydrin cross-linked starch and epichlorohydrin cross-linked dextran, i.e. Sephadex.

The amphiphilic phospholipids composed of two fatty acid chains as hydrophobic part and phosphoric acid as Hydrophilic polar end.

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B. Mandal et al (2013).4In an aqueous media the phospholipid molecules orient and self organised in planar bilayer sheets to minimize the unfavourable interaction between hydrophobic and hydrophilic part and this interaction is completely eliminated when the sheets fold over themselves to form closed concentric vesicles means Self assemble with each other.

Self assemblage of phospholipids also depends upon the Phase transition temperature of lipids as on maintaining the temperature above this transition temperature the liquid crystalline phase exits which in turn aids in mobility of acyl chains for easy assemblage of phospholipid molecules.

Various types of phospholipids used are phosphatidyl choline, phosphatidyl hydroxycholine, phosphatidyl ethanolamine, phosphatidyl serine, and phosphatidyl glycerol.The amphiphilic coating may also comprise a derivative of a phospholipid as PEG-phospholipids, and phospholipids grafted to other molecules or polymers.

Additional compounds and mixtures may also be added to the phospholipids in the amphiphilic coating as for example fatty acids, steroids (such as cholesterol), and surface active agents.

The cholesterol acts as a fluidity buffer , though it self it does not form bilayers but can be incorporated in the membrane to provide rigidity as the presence of cholesterol at temperature below the phase transition temperature aids in increasing the mobility of the acyl chains for self assemblage.

At temperature above the phase transition the cholesterol condenses the bilayer vesicles to form more rigid structure .

The cholesterol is generally aadded in very high proportion i.e upto 1:1 or 2:1 molar ratio of cholesterol to phospholipids respectively. Schematic representation of Lipid-Polymer hybrid nanoparticles with its structural components. (A) Lipoparticles with a lipid bilayer..

B. Mandal et al (2013).Advantages:The solid polymeric core acts as a cytoskeleton that provides mechanical stability, controlled morphology, biodegradability, narrow size distribution, and high available specific surface area.The lipid shell enveloping the core is biocompatible and exhibits behavior similar to that of cell membrane.Improved encapsulation of hydrophobic drugs for a number of drugs compared to liposomes or Polymericnanoparticles preparations.Lipoparticles can entrap and deliver multiple hydrophilic and hydrophobic therapeutic agents simultaneously.Optimization of the core and shell can result in sustained drug release profiles.Particles smaller than 100 nm are promising for intracellular drug targeting.

METHOD OF PREPARATION

Two-step method: The polymeric core and lipid shell are prepared separately using two independent processes after that these two components are combined by direct hydration, sonication, or extrusion to obtain the desired lipid shellpolymer core structure .

B. Mandal et al (2013).Single step Method:

1. Modified Solvent Extarction /Evaporation method: The single-step method involving nanoprecipitation and self-assembly processes. (A) Drug, polymer dissolved in organic solvent forming organic phase. (B) The organic phase is added dropwise into the aqueous phase containing phospholipids. (C) The resulting dispersion is sonicated or homogenized to obtain Lipoparticles.

B. Mandal et al (2013).2. Modified Nanoprecipitation method: In this method, firstly Polymer and hydrophilic drug are dissolved in a water miscible organic solvent. Secondly, the aqueous dispersion of Lipid- Polyethyleneglycol conjugate is prepared and prepared dispersion is heated at temperature above transition temperature.The organic solution is then added drop by drop into the aqueous solution.Mixture is then vortexed and subsequently homogenised or ultrasonicated to reduce the particle size to nanometer range and to evaporate the organic solvent.The Lipoparticles produced were purified by ultracentrifugation. DRUG LOADING and entrapment efficiency:

Many small-molecular-weight chemotherapeutic drugs, proteins, and nucleotides have been encapsulated/entrapped into these lipoparticles.The various methods of Drug loading are:

However, the drug laoding is generally expected to be better in the incorporation method as compared to the Absorption method.1. Drug Incorporation Method2. Drug Absorption MethodEntrapment Efficiency of drug depends upon:

1. Aqueous Solubility of the Drug.2. Affinity and Miscibility of the drug in both the polymer and lipid phase. 3. Amount of Lipid. 4. Aqueous Ph.5. Method of Preparation.Physicochemical characteristics:PARAMETERMETHOD OF CHARACTERIZATION Particle size distributionPhoton correlation spectroscopy(PCS) .Surface chargeZeta potential by PCS.

MorphologyTransmission electron microscopy (TEM),scanning electron microscopy.Lipid shell thicknessSmall angle x-ray scattering (SAXS), TEM. Drug loading and entrapmentHigh-performance liquid chromatography(HPLC), dialysis, centrifugation,membrane filtration.Drug releaseDialysis followed by HPLC, UV-visiblespectrophotometryAPPLICATIONS IN DRUG DELIVERY:Cancer targeting: Lipid-polymer hybrid particles are being developed for tumour selective delivery of anticancer agents.

Schematic diagram of mechanisms of intestinal drug transport from lipid-based formulations.

Sandeep et al (2013) Conclusion:This particle design uses an integrative approach by combining two types of sytem such as polymeric nanoparticles and liposomes and have features for treating various diseases, particularly cancers.

The design and development of lipid-polymer hybrid particles as drug delivery platforms requires more focussed resarch in key areas of stability, scale-up,toxicity and pharmacokinetic profiles.References:

Lian T, Ho RJY. Trends and developments in liposome drug delivery systems. J Pharm Sci 2001, 67-80.

2. Busseron Eric, Ruff Yves, Moulin Emilie and Giuseppone Nicolas. Supramolecular Self assemblies as Functional nanomaterials. RSC Publishing, 2013, 5 , 7098-7140.

Mandal Bivash, Bhattacharjee Himanshu, Mittal nivesh, Sah Hongkee, Balabathula Pavan, Thoma Lauram A, Wood George C. Coreshell-type lipidpolymer hybrid nanoparticles as a drug delivery platform. Nanomedicine: Nanotechnology, Biology, and Medicine, 9 (2013), 474-491.

4. Hai Yan Gao, Joseph SchWarz, Michael Weisspapir. Hybrid Lipid-polymer Nanoparticulate Delivery Composition. United States Patent Application Publication. US 2008/0102127 A1. May 1, 2008. 1-6.

5. Vyas S.P, KharR.K, Targeted and controlled Drug Delivery Novel Carrier Systems, chapter-5,CBS Publishers,173-179.

6.Kalepun Sandeep, Manthina Mohanvarma, PadavalaVeerabhadhra swamy. Oral lipid-baseddrugdeliverysystems an overview. Acta Pharmaceutica Sinica B 2013;3(6):362.

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