Related Experiment Video
Updated: Aug 7, 2026
10:16
Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier
Published on: February 8, 2017
"SMART" drug delivery systems: double-targeted pH-responsive pharmaceutical nanocarriers
R M Sawant1, J P Hurley, S Salmaso
1Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, USA.
Bioconjugate Chemistry
|July 20, 2006
Summary
Researchers developed pH-sensitive nanocarriers for targeted drug delivery. These smart carriers shield targeting moieties at normal pH but expose them in acidic tumor environments for enhanced cell uptake.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery Systems
Background:
- Targeted pharmaceutical carriers are crucial for effective drug delivery, especially in disease sites with altered microenvironments like tumors.
- Stimuli-responsive nanocarriers offer enhanced specificity by altering their properties in response to local cues.
- Polyethylene glycol (PEG)-based nanocarriers are widely used for their long circulation times and stealth properties.
Purpose of the Study:
- To engineer multifunctional, long-circulating nanocarriers (liposomes and micelles) that respond to local pH stimuli.
- To enable targeted delivery via antibody conjugation and enhance cellular uptake using specific peptides.
- To develop a pH-triggered release or activation mechanism for improved therapeutic efficacy.
Main Methods:
- Preparation of PEGylated liposomes and PEG-phosphatidylethanolamine (PEG-PE) micelles.
- Surface functionalization with monoclonal antimyosin antibody 2G4, biotin, or TAT peptide (TATp).
- Incorporation of a pH-sensitive hydrazone bond (PEG-Hz-PE) for degradable PEGylation.
Main Results:
- Nanocarriers exhibited shielded targeting/uptake functions at physiological pH (7.4-8.0).
- At acidic pH (5.0-6.0), the PEG shell degraded, exposing biotin for avidin column retention and TATp for enhanced cellular internalization.
- High specific binding to myosin was observed at pH 7.4-8.0, while pH-dependent avidin binding and cell uptake were demonstrated.
Conclusions:
- The developed nanocarriers represent a novel approach to stimuli-responsive drug delivery.
- pH-triggered de-shielding of functional moieties enhances targeting and cellular uptake in acidic environments.
- This technology is a promising first step towards multifunctional, stimuli-sensitive pharmaceutical nanocarriers.
Related Concept Videos
01:24Modified-Release Drug Delivery Systems: Site-Targeted
Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.
01:24Site-Targeted Drug Delivery Systems: Polymeric Carriers
Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
01:23Modified-Release Drug Delivery Systems: Classification
Modified-release drug delivery systems improve drug efficacy and minimize side effects by controlling the rate and location of drug release. These systems fall into three categories: rate-programmed, stimuli-activated, and site-targeted.Rate-programmed systems release drugs at a predetermined rate, maintaining consistent therapeutic levels and reducing fluctuations that could lead to toxicity or subtherapeutic effects. These systems use polymeric matrices, reservoir-based designs, or osmotic...
01:30Modified-Release Drug Delivery Systems: Stimuli-Activated
Stimuli-activated drug delivery systems are designed to release drugs in response to specific physical, chemical, or biological stimuli. These systems often utilize hydrogels—three-dimensional, hydrophilic polymer networks capable of swelling in aqueous environments and retaining significant fluid volumes. Upon exposure to particular stimuli, these hydrogels undergo structural transitions that allow the embedded drug to be released. Due to this adaptive behavior, such systems are also called...
01:26Oral Drug Delivery Systems: Continuous-Release Systems
Continuous-release drug delivery systems offer a strategic approach to maintaining therapeutic drug levels over extended periods following oral administration. By modulating the release rate of active pharmaceutical ingredients, these systems minimize fluctuations in plasma concentrations, which enhances clinical efficacy and reduces the need for frequent dosing. Such characteristics make them particularly advantageous in managing chronic diseases where patient adherence and stable drug...
01:23Oral Drug Delivery Systems: Introduction
Oral drug delivery is the most common route of administration due to its convenience, cost-effectiveness, and high patient compliance. It enables precise formulation to ensure proper drug dosage and bioavailability. The development of oral dosage forms considers drug properties such as solubility, stability, and absorption to optimize therapeutic efficacy.Tablets, capsules, liquids, and chewable formulations enhance drug stability, mask undesirable tastes, and improve patient experience.