Aloe Derived Nanovesicles Based Novel Drug Delivery Systems Study

Plant derived nanovesicles(PDNVs)with the advantages of sustainability,natural availability,safety and cost efficiency have been widely attracted attention of people in drug delivery filed.This paper proposed an optimized method for nanovesilces isolation from aloe(ADNVs),and reasonably analyzed their feasibility as drug carriers.Then the ADNVs were used as nanocarriers for drug delivery and effective cancer therapy.Chapter 1,isolating the nanovesicles derived from aole rind and gel(r ADNVs and g ADNVs)by squeezing and ultracentrifugation,and optimizing their isolating method.We found that the vesicle aggregation or deformation was effectively reduced by simply controlling the centrifugation time within 20 min,which was benefical for maintaining the structure integrity and dispersion of vesicles.And the viscosity of aloe juice adjusted could improve the yield of vesicles effectively.At the viscosity of 2.98 m Pa·S and 1.57 m Pa·S respectively,the higher yield of r ADNVs and g ADNVs were isolated.Then,the morphology,particle size and zeta potential of them were analyzed.The g ADNVs and r ADNVs were at the average size of 138.7 nm and 220 nm with distinct elliptic or saucer-like phospholipid bilayer and the zeta potential of-8.9 m V and-7.4 m V respectively.These properties were similar to the human exosmoes.Then the proteins,lipids and phytochemicals of them were further analyzed.We found that both vesicles were rich in proteins(such as heat shock protein,annexin families,etc.)and lipids(such as ceramide,etc.),also the aloe emodin,aloesin were found in vesicles.These ingredients were beneficial for maintaining the stability of vesicles.Chapters 2,basing on the study results of chapters 1,the g ADNVs were selected as research objects.Their stored stability,antioxidant and antisolubilizer properties were explored to verify their feasibility as drug carriers.On this basis,g ADNVs were further used for ICG loading.We found that ICG loaded in g ADNVs was stable in serum and high temperture and could be reten for longer term(more than 90 % ICG retention after storage for 30 days),which was better than multi-component liposomes(Lips).The prepared ICG/g ADNVs induced effective melanoma cell damage and tumor ablation under laser irradiation.In addition,we further explored the transdermal properties of g ADNVs,and found that g ADNVs could effectively penetrate the cuticle barrier and deliver drugs to the dermis to a depth of 200 μm.It made g ADNVs enable to be a promising new mild and non-invasive transdermal drug delivery system for the effective treatment of superficial skin cancer such as melanoma.Chapters 3,using g ADNVs as carriers for DOX and ICG co-loading,and then modifying with the intergrin targeted peptide(Arg-Gly-Asp,RGD)by similarityintermiscibility theory for targeted combination therapy of breast cancer.We found that there was a π-π stacking interaction between DOX and ICG.It can turn “competitive”relationship of ICG and DOX inside g ADNVs into “cooperative” and enhance drug loading efficiency.Then,the g ADNVs were further modified with RGD and obtained the dual drug codelivery nanosystem(DOX/ICG/g ADNVs-RGD,DIARs).DIARs was well stable and leakproof,which could play a photothermal effect and trigger membrane rupture then accelerate the release of DOX under laser irradiation.Meanwhile,with the help of RGD,DIARs exhibited high tumor-targeting capability,which could cooperate with chemotherapy and phototherapy to inhibit cell growth and migration,thus achieving effective treatment for breast cancer.