Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 71, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2022.103295
Keywords
Doxorubicin; Vincristine; PEGylated liposomes; Dual drug liposomes; Transmembrane gradient; Ethanolic injection
Categories
Funding
- Sun Pharmaceutical Industries Limited
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The study evaluated the critical factors affecting the properties of nanoliposomes and analyzed their impact through univariate and multivariate studies. The optimized nanoliposomes showed high encapsulation efficiency, appropriate particle size, surface charge, and controlled release.
Rationale-based modulation of physico-chemical properties is critical towards design of optimal liposomal for-mulations having desired pharmacokinetic and pharmacodynamic profiles. The aim of the study was evaluation of critical formulation factors which may influence the encapsulation efficiency, hydrodynamic diameter, elec-trokinetic potential, internal morphology and drug release profiles of nanoliposomes. Doxorubicin and Vincristine were actively co-loaded in preformed PEGylated liposomes prepared using ethanolic injection. The variation of independent factors (transmembrane gradient, lipid-molar ratio, drug loading temperature, phos-phatidylcholine chain length, sequence of drug addition, drug loading pH, external medium) on dependent variables were evaluated using array of univariate analysis with key determinants further analysed using multivariate studies. Univariate study results showed that concentration of ammonium sulphate, drug loading pH and lipid-molar ratio had significant effect on dependent variables. Nanoliposomes prepared in multivariate studies exhibited high encapsulation efficiency (> 95%), particle size (Z-average: 106.55 +/- 6.63 nm) and surface charge of-5.55 +/- 2.77 mV. The optimized nanoliposomes exhibited characteristic coffee-bean shaped morphology showing doxorubicin nanoprecipitation and electron dense vincristine presence in internal aqueous phase that exhibited controlled in-vitro release of both drugs unaffected by presence of each other. Further, an attempt was made to correlate these results to the chemical structure and physicochemical properties of the drugs.
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