| Cyclodextrins(CYD) and liposomes have been used in recent years as drug delivery vehicles, improving the bioavailability and therapeutic efficacy of many poorly water soluble drugs. Liposomes can encapsulate the lipophilic drugs in the phospholipid bilayer and alter the biodistribution of drugs. However, incorporation of lipophilic drugs into lipid bilayers of liposomes is often limited in terms of drug-to-lipid mass ration and drug choice, can interfere with bilayer formation and its stability. CYD can accommodate water insoluble drugs in their cavities to form inclusion complexes. The formed inclusion complex has increased solubility, stability and pharmacological activity. Entrapping water-soluble drug/CYD inclusion complexes into the aqueous phase of liposomes combines the advantages of certain properties of cyclodextrins and liposomes into a single system to circumvent problems associated with both systems.In our present study, Indomethacin(IDM) was used as lipophilic drug model. Inclusion complexes of IDM with β -cyclodextrin( β -CD) and hydropropyl- β -cyclodextrin(HP β -CD) were formed by the saturation solution method, freeze-dried method, grinding method and ultrasion method,respectively. However, the freeze-dried method was the best among these methods on the basis of the load efficiency, yield and entrapment value. In brief, -CD or HP 3 -CD was added to warm distilled water containing IDM under continuous stirring. The mixtures were allowed to stir for up to 2.5hr in absence of light at room temperature and then filter through a 0.45um membrane filter. The filtrate were freeze-dried to yield amorphous powder. In each case the amount of the IDM in inclusion complexes was estimated by ultraviolet spectrometry at 320nm. The load efficiency, yield and entrapment value were 10.5%, 86.0%,75.3% for IDM- p -CD inclusion complexes, 9.7%, 83.9%, 73.6% for IDM- -CD inclusion complexes, respectively. Inclusion complexes formation was verified by differential thermal analysis (DTA) and infrared spectroscopy. In the DTA endothermal peak of IDM disappeared in the inclusion complexes and the inclusion complexes appeared new endotherrnai peak (199.1 for IDM- CD inclusion complexes and 197.1'C for IDM-CD inclusion complexes ) due to interaction of IDM with CD or HP CD . In addition, IR spectra revealed that the IDM carbonyl peaks were shifted from 1700 cm"'and 1720 cm"1 to 1590cm"1 and 1680 cm"1 due to inclusion complexes formation. The phase-solubility experiment was performed by the method reported by Higuchi and Connors. The phase-solubility profiles indicated that the inclusion complexes were formed at 1:1 molar ration of drug and CD and the phase-solubility profiles belong to class-At diagrams, and the stability constants were 192 M"'and 237 M"!, respectively.The liposomes incorporating inclusion complex were prepared using dehydration-rehydration vesicle method due to the high entrapment efficiency. In brief, small unilamellar vesicles(SUV) made from soy phosphatidylcholine and cholesterol (2:l,w/w) were mixed with complexed IDM dissolved in distilled water and freeze-dried., multilamellar dehydration-rehydration vesicleswere formed through rehydrated with 0.9%NaCl solution by vortexing. The highest IDM entrapment value was achieved for liposomes when the lipid concentration was 30mg/ml, drug:lipid wasl:7(w/w), freeze-dried volume was 10ml. The entrapment values were 55.6% (the liposomes entrapment of 3 -CD inclusion complexes) and 57.9% (the liposomes entrapment of 3 -CD inclusion complexes). Artificial neural network was used to analysis the entrapment values of liposomes, it can predict the entrapment values of the liposomes encapsulating inclusion complexes on the basis of the materials and technology.The mean diameter and size distribution were determined by laser light scattering .The mean diameter of particles were 4.2|jm(the liposomes entrapment of P -CD inclusion complexes), 3.6[j.m(the liposomes entrapment of HP 3 -CD inclusion complexes), 4.9p.m(the liposomes entrapment o... |
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