Negative Impact of Paclitaxel Crystallization on Hydrogels and Novel Approaches for Anticancer Drug Delivery Systems

Castro, Javier S.; Tapia, L.V.; Silveyra, Rocio A.; Martínez, Carlos A.; Deymier, Pierre A.

doi:10.5772/23372

Cited by 1 publication

(2 citation statements)

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“…The local delivery of PTX has limited clinical applications due to the crystallization of PTX within the delivery matrix. 77,78 Such crystallization has been the bottleneck in effectively encapsulating PTX into the drug-carrier systems. 79 When PTX molecules are individually entrapped within the hydrophobic region of bilayers they are in a metastable state 80 and tend to self-aggregate precipitating out into solution to form a more stable crystalline form.…”

Section: Resultsmentioning

confidence: 99%

“…The most common adverse effects include infusion-related reactions and neutropenia. , Accordingly, local drug delivery to a targeted and focal site of disease (termed surface- or substrate-mediated drug delivery) can be a preferable option for delivering PTX, as in drug-eluting medical implants. ,, Second, we hypothesized that the unique structure of PTX would maximize the benefit of having domain structures in films. The local delivery of PTX has limited clinical applications due to the crystallization of PTX within the delivery matrix. , Such crystallization has been the bottleneck in effectively encapsulating PTX into the drug-carrier systems . When PTX molecules are individually entrapped within the hydrophobic region of bilayers they are in a metastable state and tend to self-aggregate precipitating out into solution to form a more stable crystalline form. − …”

Section: Resultsmentioning

confidence: 99%

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Three-Dimensional Microphase Separation and Synergistic Permeability in Stacked Lipid–Polymer Hybrid Membranes

2017

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We present new structures of soft-material thin films that augment the functionality of substrate-mediated delivery systems. A hybrid material composed of phospholipids and block copolymers adopts a multilayered membrane structure supported on a solid surface. The hybrid films comprise intentional intramembrane heterogeneities that register across multilayers. These stacked domains convey unprecedented enhancement and control of permeability of solutes across micrometer-thick films. Using grazing incidence X-ray scattering, phase contrast atomic force microscopy, and confocal microscopy, we observed that in each lamella, lipid and polymers partition unevenly within the membrane plane segregating into lipid- or polymer-rich domains. Interestingly, we found evidence that like-domains align in registry across multilayers, thereby making phase separation three-dimensional. Phase boundaries exist over extended length scales to compensate the height mismatch between lipid and polymer molecules. We show that microphase separation in hybrid films can be exploited to augment the capability of drug-eluting substrates. Lipid–polymer hybrid films loaded with paclitaxel show synergistic permeability of drug compared to single-component counterparts. We present a thorough structural study of stacked lipid–polymer hybrid membranes and propose that the presence of registered domains and domain boundaries impart enhanced drug release functionality. This work offers new perspectives in designing thin films for controlled delivery applications.

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