liposomes and nanoparticles drug delivery system

this presentation includes the intro duction to targeted drug delivery systems using nanoparticulate systems like liposomes, nanoparticles, mechanism of action, types, preparation, advantages, applications

1. Liposomes and nanoparticles in drug delivery By: Shreya Bhat, 2BA18BT017  8th semester  B.E Biotechnology Faculty: Dr. Madhumala Y. Basaveshwar Engineering College,  Bagalkote 587103. Seminar on 

2. Why liposomes and nanoparticles? Nanodrugs like these are used in chemotherapeutic drugs in cancer. Advantageous cause they have improved pharmacokinetic properties, controlled and sustained release, low toxicity. Commercially available are liposomal doxil , albumin nano-particle-based- abraxane . Used in multidrug resistant cancers  Low cardiotoxicity. Higher efficacy low toxicity.

3. Introduction liposomes are closed spherical vesicles consisting of a lipid bilayer that encapsulates an aqueous phase in which drugs can be stored.  The liposome diameter varies from 400 nm to 2.5 mm.  Nanoparticles (NPs), which are particles ranging in size from 1 to 100 nm, exhibit unique physical and chemical properties that can be exploited for drug delivery by conjugation with drugs. Both these emerging nanoscale drug delivery systems can be used to improve current treatment regimens.

4. Advantages of nanoscale drug delivery system It acts efficiently and proficiently on a specific target..  Biodegradability and biocompatibility so that the unloaded drug carrier system gets metabolized by the body without letting the trace elements to remain in the body which may emerge into new chronic disease.

5. liposomes Liposomes and NPs are just beginning to make an impact in chemotherapy owing to the dual drive to reduce the toxicity and side effects of existing treatments and increase efficacy by selective targeting of tumours .

6. Why liposomes? ( 1) Because they are noncovalent aggregates, their lipid composition, size, and electric charge can be easily controlled. (2) Their modification, with surface polymers, carbohydrates, and antibodies, can be easily achieved to facilitate targeting (3) Liposomes have almost no toxicity and low angiogenicity . ( 4) Liposomes can be biodegradable and metabolized in vivo.  (5) Properties such as membrane permeability can be controlled to some extent Liposomes can hold various types of solutes with different properties and molecular weights, such as fat-soluble molecules, water-soluble molecules, and amphiphilic molecules.

7. These nanostructures can be categorized into five major varieties, namely (1) polymer-stabilized liposomes  (2) nanoparticle-stabilized liposomes  (3) core-shell lipid polymer hybrid nanoparticles  (4) natural membrane-derived vesicles   (5) natural membrane coated nanoparticles.

8. Mechanism of liposomal drug delivery. a liposome encapsulates a region of aqueous medium inside a hydrophobic membrane. Dissolved hydrophilic solutes cannot pass through the lipids. Hydrophobic chemicals can be dissolved into the membrane, and in this way liposome can carry both hydrophobic molecules and hydrophilic molecules. To deliver the molecules to the sites of action, the lipid bilayer fuses with the other bilayers such as the cell membrane, thus delivering the liposome contents.

9. Methods of liposome preparation Passive loading: Encapsulating the drug while manufacturing. Active remote loading: Certain types of compounds with ionizable groups and those with water or lipid solubility can be introduced into the liposomes after the formation of the intact vesicles.

10. METHODS OF LIPOSOME PREPERATION

11. Method of liposome preparation and drug loading.

12. 1. Liposome as drug delivery vehicle

13. 2. liposome as vaccine carrier.

14. Liposome in tumor therapy. liposomes as drug carriers can be administrated I.V route. If liposome is modified more hydrophilic, with lipids their circulation time in blood stream increases. These are called stealth liposomes, used as carriers for hydrophilic anti-cancer drugs(Doxorubicin, Mitoxantrone) In this form they can extravasate the tumour vascular endothelium

15. Liposomes in gene delivery The nonviral vector systems, are especially engineered liposome such as pH sensitive liposomes, cationic liposomes, fusogenic liposome, genosomes , lipoplex, and lipopolyplex have been extensively investigated for their gene delivery potential. Lipoplex aggregates  with DNA to form large and heterogenous liposomes. Which is composed of liposomes+polycation+DNA . Genosomes are complex formulations of DNA with various cationic liposomes.

16. Liposomes as artificial blood surrogates Liposome encapsulated hemoglobin products can be used as artificial RBC. Sterically stabilized liposome bearing hemoglobin are better oxygen carriers. These have low toxicity, less platelet activation  aggregation and less heamostatic generation.

17. Therapeutic applications of liposomes

18. Nanoparticles in drug delivery. These nano-sized objects, “nanoparticles” . are in the range of 1-100nm. And has unique physiochemical properties which have the capacity in treating therapeutic applications This rapidly growing field requires cross disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases such as cancer. Nanoparticles can mimic or alter biological processes (e.g., infection, tissue engineering, de novo synthesis, etc.). These devices include, but are not limited to, functionalized carbon nanotubes, nanomachines (e.g., constructed from interchangeable DNA parts and DNA scaffolds), nanofibers, self-assembling polymeric nano constructs, nanomembranes, and nano-sized silicon chips for drug, protein, nucleic acid, or peptide delivery and release, and biosensors and laboratory diagnostics. 

19. Nanoparticles. They are the particulate dispersions or solid particles drug carrier that may or may not be biodegradable. The drug is dissolved, entrapped, encapsulated to the matrix. The term nanoparticle is a combined  name for both nanosphere and nanocapsules .

20. Drug is confirmed to a cavity surrounded by a unique polymer membrane called nano-capsules are matrix system in which the drug is physically and uniformly dispersed.

21. Nanoparticles have significant advantage over conventional and traditional drug delivery system. Nanoparticles are control and sustain release form at the site of localisation , they alter organ distribution of drug compound. They have the superb bioavailability, therapeutic efficacy and reduce side effects. Nanoparticles can be administer by various routes including oral, nasal, parental, intra-ocular etc. Nanoparticles enhance the aqous solubility of poorly soluble drug, which improves bioavailability of the drug. As a targeted drug carrier nanoparticles reduce drug toxicity and enhance efficient drug distribution. Useful to diagnose various diseases.

22. Preparation techniques of nanoparticles.

23. Pharmaceutical aspects of nanoparticles.

24. Need to control drug delivery

25. Factors affecting in the selection of material for preparation of nanoparticles. Size and shape of the nanoparticle Intrinsic and extrinsic properties of the drug. Surface characteristics such as charge and permeability. Degree of bioavailability, biodegradability and biocompatibility. Toxicity of the trace elements. Antigenecity of the final product.

26. Nanoparticle delivery system Nanoparticles are solid, colloidal particles consisting of macromolecular substances that vary in size from 10 nm to 1000 nm ( Kreuter et al., 1994a ). However, particles >200 nm are not heavily pursued and nanomedicine often refers to devices <200 nm (i.e., the width of microcapillaries). Typically, the drug of interest is dissolved, entrapped, adsorbed, attached and/or encapsulated into or onto a nano-matrix. Depending on the method of preparation nanoparticles, nanospheres, or nanocapsules can be constructed to possess different properties and release characteristics for the best delivery or encapsulation of the therapeutic agent

27. Characteristics Important for Drug Delivery using Nanoparticles    Particle size and size distribution are the most important characteristics of nanoparticles. They determine the in vivo distribution, biological fate, toxicity, and targeting ability of these delivery systems. In addition, they can influence drug loading, drug release, and stability of nanoparticles. Many studies have demonstrated that nanoparticles have a number of advantages over microparticles. nanoparticles have relatively high cell uptake when compared to microparticles and are available to a wider range of cellular and intracellular targets due to their small size and mobility.

28. Continued.. Drug release also is affected by particle size. Smaller particles have a larger surface area-to- volume ratio; therefore, most of the drug associated with small particles would be at or near the particle surface, leading to faster drug release. In contrast, larger particles have large cores, which allow more drug to be encapsulated per particle and give slower release

29. Surface properties of nanoparticles The zeta potential of a nanoparticle is commonly used to characterize the surface charge property of nanoparticles.  It reflects the electrical potential of particles and is influenced by the composition of the particle and the medium in which it is dispersed. Nanoparticles with a zeta potential above ± 30 mV have been shown to be stable in suspension, as the surface charge prevents aggregation of the particles. The zeta potential also can be used to determine whether a charged active material is encapsulated within the center of the nanoparticle or on the surface

30. Drug loading  Drug loading can be accomplished by two methods.  The incorporation method requires the drug to be incorporated at the time of nanoparticle formulation. The adsorption/absorption methods calls for absorption of the drug after nanoparticle formation; this is achieved by intubating the nano-carrier with a concentrated drug solution. Drug loading and entrapment efficiency depend on drug solubility in the excipient matrix material (solid polymer or liquid dispersion agent), which is related to the matrix composition, molecular weight, drug-polymer interactions, and the presence of end functional groups 

31. Drug release. It is important to consider both drug release and polymer biodegradation when developing a nanoparticulate delivery system. In general, the drug release rate depends on: (1) drug solubility;  (2) desorption of the surface-bound or adsorbed drug;  (3) drug diffusion through the nanoparticle matrix;  (4) nanoparticle matrix erosion or degradation; (5) the combination of erosion and diffusion processes. Hence, solubility, diffusion, and biodegradation of the particle matrix govern the release process

32. Targeted drug delivery   Targeted delivery can be actively or passively achieved. Active targeting requires the therapeutic agent to be achieved by conjugating the therapeutic agent or carrier system to a tissue or cell-specific ligand  Passive targeting is achieved by incorporating the therapeutic agent into a macromolecule or nanoparticle that passively reaches the target organ. Drugs encapsulated in nanoparticles or drugs coupled to macromolecules can passively target tumors through the EPR effect. Alternatively, catheters can be used to infuse nanoparticles to the target organ or tissues

33. Nanoparticle recovery and drug incorporation efficiency. Entrapment efficiency: it is calculated with respect to the initial amount of drug added during the formulation development. It can be determined by direct/indirect method using the following formula; % drug entrapped= total added drug-free drug   ×100                                   Total added drug 

34. Contd.. Drug loading: it is calculated with respect with respect the formulation I.e. amount of the drug present in the final formulation.it ca be determined by direct/indirect using the following formula; % drug loading= Total weight encapsulated drug into the formulation ×100                                       Total weight of final formulation        

35. Carrier drug interactions and physical state characterisation Differential scanning calorimetry : it is preliminary technique for the identification of any possible interaction between formulation components. Thermograms of each constituent of the formulations are recorded and compared with that of the final formulation; appearance of any extra peak or dissapearance of existing peak shows the interaction among the components.

36. FTIR: it is a confirmatory analytical tool to define the interaction between formulation components. FTIR spectra of each constituent of the formulations are recorded and compared with that of the final formulation; appearance of any extra peak or dissapearance of existing peak shows the interacted among the components. Xray diffraction studies: powder X-ray diffraction may be readily used to determine the crystal structure of simple lattice structures. In this technique diffraction of X-rays, at a specific range of angle, is observed.

37. Therapeutic Applications of Nanoparticles