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Introduction
Polymer-lipid Hybrid systems (PLHs) are solid, submicron particles which are composed of at least two components: polymer and lipid.
This multilayered colloidal delivery system comprises a core of natural hydrophilic polymer which is made up of cross-linked polysaccharide or a cross-linked oligosaccharide.
The core is partially coated or completely coated with a layer which is either a lipid layer or an amphiphilic compound such as phospholipid.
This particulate system have been introduced in an effort to mitigate some limitations associated with lipid based nanoparticles and polymeric nanoparticles for oral drug delivery.
Advantages of PLHs
The polymeric system acts as a cytoskeleton that provides mechanical stability, controlled morphology, biodegradability, narrow size distribution, and high available specific surface area.
The lipidic system enveloping the core is biocompatible and exhibits behavior similar to that of cell membrane.
Improved encapsulation of various drugs compared to polymeric or lipid-based nanoparticulate preparations.
It can entrap and deliver multiple hydrophilic and hydrophobic therapeutic agents simultaneously.
Optimization of the core and shell can result into desired sustained drug release profiles.
Particles smaller than 100 nm are promising for intracellular drug targeting.
Biopharmaceutic challenges in oral drug delivery
Rationale designing of oral formulations for various therapeutic agent consider some factors which may play a decisive role in successful oral absorption of drug include aqueous solubility, stability in the GI tract, permeability through intestinal epithelia, and pre-systemic metabolism.
There are numerous issues obstructing the successful oral drug delivery for various therapeutic agents that can be categorized into three main groups: physicochemical barrier, physiological barriers and biochemical barriers.
Type of polymer-lipid hybrid systems
PLHs classified into three types:
Polymer-core lipid shell hybrid system
Lipid-core polymer-shell hybrid system
Matrix type polymer lipid hybrid
Polymer-core lipid shell hybrid system
Polymer-core lipid-shell systems consists
a polymer core
a single layer or multiple layers of lipid
Beneficial effect of lipid shell
Inhibits water penetration into the polymeric core
Prevents drug leakage
Modulates polymer degradation
Sustains drug release
Polymer may aid in structural integrity of lipid shell.
Applied examples in oral delivery includes
Chitosan lipid nanoparticles
Poly (lactic-co-glycolic acid)-phospholipid nanoparticles
Lipid-core polymer-shell hybrid system
As the name indicates, lipid-core polymer-shell systems typically consist of a lipid core surrounded by one or multiple polymer layers.
In this system
Lipid core: -accommodates the active ingredient
Polymer shell: -improves the stability of the lipid core
-confront specific biological barriers
Examples includes:
Chitosan-coated lipid nanoparticles
PEGylated lipid nanoparticles
Matrix type PLHs: nano-in-micro type hybrid
Nano-in-micro type hybrid systems can be prepared by microencapsulation technique.
Microencapsulation is a good approach to encapsulate lipid-based nano carriers with a solid-state matrix to enhance formulation stability as well as to facilitate various desirable biopharmaceutical functions.
Example includes PLGA nanocapsules embedded in enteric coated microparticles.
Single-step method
The single-step method involves nano-precipitation and self-assembly processes.
Drug, polymer dissolved in organic solvent forming organic phase.
The organic phase is added drop wise into the aqueous phase containing phospholipids.
The resulting dispersion is sonicated or homogenized to obtain PLHs.
Two-step method
The polymeric system and lipid based system are prepared separately using two independent processes after that these two components are combined by direct hydration, sonication, or extrusion to obtain the desired PLHs.
Characterization of PLHs
Significance of PLHs in oral drug delivery
PLHs increases the drug encapsulation efficiency, modulates the drug release and improve cellular uptake.
PLHs is used to protect various labile therapeutics from enzymatic degradation during GIT transit and improve the permeation through GI barriers.
Many chemotherapeutics suffer from low oral bioavailability due to intrinsic physicochemical characteristics and substrate for P-gp. Such an issue can be effectively overcome by encapsulating the chemotherapeutics in hybrid carrier system.
Conclusion
PLHs design exploited an integrative approach by combining two types of system (polymeric and lipid-based system) to overcome the various challenges in oral drug delivery.
They are used for oral delivery of various therapeutics like gene, nucleic acids, proteins & peptides also.
The design and development of PLHs as an oral drug delivery platforms requires more focused research in key areas of stability, scale-up, toxicity and pharmacokinetic profiles.