Lipid based drug delivery systems Lipid Lipid (solid） (liquid) Lipid nanoparticle Nanoemulsion Liposome
1 Lipid based drug delivery systems Lipid nanoparticle Nanoemulsion Liposome
Inner aqueous compartment Bilayer membrane Fatty G acid lipid Fatty acid Phosphate Alcohol CHs CHs Cholesterol CHs HO
2 lipid Cholesterol Cholesterol
(A) Phosphoglyceride 8 Sphingomyelin (B) Archaeal lipid Shorthand depiction Headgroup nompatidylchollne ( +-CHCHN'(CHa3 CH opaiythotmne (P) Pnosphatidlc acld (PA) ←州 +CH2CH-N'H3 coo' 上 CHCH(OH)CH2OH otyinoalt(P OH Salurated和竹y acids Acyl chain Laurie (12-0) CHa(CH2)10COOH yriatic(14:的 CH3/CHa)+2COOH Palmitic (1:0) CH3(CH2)COOH Stearic(18:0) CHa(CH2)1ECOOH Unsaturated fatty aclds Paimitelele [1C:140) CH(CHJ.CH-CH(CHJ/COOH Olele (18:149) CHa(CH2)7CH-CH(CH2.COOH Linoiele (10:209.12) CHa(CH2aCH-CHCH CH-CH(CH2)COOH
3
Relevant lipid biophysics Determination of packing parameter(PP)of amphiphiles P determines the particle form as a result of self association of amphiphiles P-cross section of hydrophobic region cross section of hydrophilic region =Vlal V volume of the hydrophobic region a effective area per headgroup(hydrophilic region) length of the hydrophobic region Lipids Shape Organization Phase Soaps lsotropic Detergents hexagonal I Lysophospholipids ?7 Inverted cone P<1g-%s Phosphatidyl- choline serine -inositol Lamellar Sphingomyelin 是日 (Cubic) Dicetylphosphate Cylinder DODAC P~1 Bilayer Phosphatidyl- ethanolamine Phosphatidic acid Reverse Cholesterol Ao micelles hexagonal量 Cardiolipin Lipid A P>1 Trsaea Mixtures Lysophosphatidyl- chotne and 阴) Lamellar Phosphatidyl- cthanolamine P-1
4 Determination of packing parameter (PP) of amphiphiles P determines the particle form as a result of self association of amphiphiles P = cross section of hydrophobic region cross section of hydrophilic region V volume of the hydrophobic region a effective area per headgroup (hydrophilic region) l length of the hydrophobic region l V a Relevant lipid biophysics =V/al
Surfctant Phase Behavior micelle hexagoral reverse hexagunal reverse micelle Commercial liposome/lipid complex-based products US-FDA approved for human use(injectable drugs) Product Route of injection Drug Particle type Approved Indication Ambisome i.v. Amphotericin B Liposome (chemotherapy) (LUV) Severe fungal infections Abelcet iv. Amphotericin B Lipid complex (chemotherapy) (ribbons) Severe fungal infections Amphotec iv. Amphotericin B Lipid complex (chemotherapy) (disc) Severe fungal infections DaunoXome iv Daunorubicin Liposome (chemotherapy) (LUV) Blood tumors Doxil iv. Doxorubicin PEGylated(sterically stabilized)SUV-LUV Kaposi's sarcoma (chemotherapy) liposome Ovarian/Breast cancer Visudyne* iv. Benzoprophyrin Liposomes Age-related molecular degeneration(AMD) Multivesicular large Lymphomatos Depocyt Spinal Cytarabine liposomes meningitis (late stage lymphoma) 12-23um DepoDur Epidural Morphine sulfate Multivesicular Pain management liposomes
5 Commercial liposome/lipid complex-based products US-FDA approved for human use (injectable drugs) Product Route of injection Ambisome i.v. i.v. i.v. i.v. i.v. i.v. Depocyt Spinal Cytarabine Multivesicular large liposomes Lymphomatos meningitis (late stage lymphoma) DepoDur Epidural Morphine sulfate 12-23 μm Multivesicular liposomes Amphotericin B (chemotherapy) Liposome (LUV) Severe fungal infections Pain management Abelcet Amphotericin B (chemotherapy) Lipid complex (ribbons) Severe fungal infections Amphotec Amphotericin B (chemotherapy) Lipid complex (disc) Severe fungal infections DaunoXome Daunorubicin (chemotherapy) Liposome (LUV) Blood tumors Doxil Doxorubicin (chemotherapy) PEGylated (sterically stabilized) SUV-LUV liposome Kaposi’s sarcoma Ovarian/Breast cancer Visudyne* Benzoprophyrin Liposomes Age-related molecular degeneration (AMD) Drug Particle type Approved Indication