Cyclodextrins or liposomes?

education, ,

When thinking about advanced drug delivery systems, two names always come up: cyclodextrins (CDs) and liposomes.

Both are powerful tools – but the right choice depends on asking the right questions.

Here are the top 5 considerations:

1️⃣ Solubility & Stability – Does the API suffer from poor aqueous solubility or chemical instability?
→ CDs excel in solubilizing small molecules; liposomes offer protection and controlled release.

2️⃣ Cargo Type – Are we delivering a small, lipophilic drug or a larger biomolecule (RNA, peptide, protein)?
→ CDs are ideal for small hydrophobic compounds; liposomes handle complex biologics.

3️⃣ Release Profile – Do we need immediate solubilization or sustained/targeted release?
→ CDs act fast; liposomes can be tuned for controlled or site-specific delivery.

4️⃣ Biocompatibility & Safety – Which system aligns better with the intended route of administration (oral, IV, topical)?
→ Both are biocompatible, but formulation history, excipient acceptance, and dose levels matter.

5️⃣ Scalability & Cost – Can the system be manufactured reliably and at scale?
→ CDs often offer simpler, cost-effective formulations; liposomes require more complex processes but enable versatile applications.

The truth is: it’s not about which is “better”—it’s about matching the delivery system to the therapeutic challenge.

At CarboHyde, we’re passionate about cyclodextrins, but we also recognize where liposomes shine. That is why Tamas Kiss, created this great comparison.

The future of drug delivery will likely see hybrid solutions, combining the strengths of both worlds.

CD_vs_liposomesDownload

Drugs in Cyclodextrin in Liposomes: How a Suitable Formulation of an Active Substance Can Improve Its Efficiency?

drug delivery, Today's cyclodextrin,

today’s cyclodextrin:
Drugs in Cyclodextrin in Liposomes: How a Suitable Formulation of an Active Substance Can Improve Its Efficiency?

Great paper from Prof Geraldine Gouhier, François Estour and colleagues from Université de Rouen on the design of new drug delivery systems.

Liposome formulations are pivotal in medicine for their ability to improve drug solubility, allowing for targeted delivery directly to disease sites, which minimizes side effects. They enable controlled and sustained release of medications, reducing dosage frequency. Their ability to encapsulate a variety of substances makes them versatile for different treatments, significantly reducing toxicity and enhancing the stability of drugs, especially sensitive biological compounds. This ensures a more effective and safer therapeutic approach.

Discover how the innovative “drug-in-cyclodextrin-in-liposomes” method is revolutionizing drug delivery! Enhancing drug stability & release, this latest review dives into how these nano-carriers improve the efficacy of various drugs. 🧬💊

Processes | Free Full-Text | Drugs in Cyclodextrin in Liposomes: How a Suitable Formulation of an Active Substance Can Improve Its Efficiency? (mdpi.com)


Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

drug delivery, Today's cyclodextrin,

Today’s cyclodextrin is a smart and very practical study, highlighting how different cyclodextrins added to a liposomal formulation could influence the release of the active load.

The results demonstrated that the CDs effect on the membrane depends on the CD type, CD concentration, and membrane cholesterol content. The investigated CDs exhibited an instantaneous permeabilizing effect promoting vesicle leakage of API from the various membranes; this effect increased with CDs concentration. Among the studied CDs, α-CD, β-CD, and RAMEB were the most permeabilizing CDs on the different membranes.

Ghenwa Nasr, Helene Greige, Sophie Fourmentin, Abdelhamid ELAISSARI, Nathalie Khreich

BJOC – Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration (beilstein-journals.org)

Cyclodextrin-Coordinated Liposome-in-Gel for Transcutaneous Quercetin Delivery for Psoriasis Treatment

Today's cyclodextrin,

Today’s cyclodextrin:
This is some fancy drug delivery: Cyclodextrin-Coordinated Liposome-in-Gel
Psoriasis is a chronic inflammatory skin disease that is difficult to treat. Quercetin is a dietary flavonoid known for its anti-inflammatory effects and safe use in humans. However, the topical application of quercetin for psoriasis treatment presents a significant challenge due to its poor water solubility and low stability in semisolid preparations, where it tends to recrystallize. This work presents a novel liposome-in-gel formulation for the quercetin-based topical treatment of psoriasis. The quercetin-loading liposomes are stabilized by hydroxypropyl-β-cyclodextrin (HPCD), which interacts with phospholipids via hydrogen bonding to form a layer of an HPCD coating on the liposome interface, thus resulting in improved stability.
The in vivo results showed that the topical QT HPCD-liposome-in-gel improved the treatment efficacy of psoriatic plaque compared to free QT. It alleviated the symptoms of skin thickening and downregulated proinflammatory cytokines, including TNF-α, IL-17A, and IL-1β. The results suggested that the HPCD-coordinated liposome-in-gel system could be a stable carrier for topical QT therapy with good potential in psoriasis treatment.

Cyclodextrin-Coordinated Liposome-in-Gel for Transcutaneous Quercetin Delivery for Psoriasis Treatment | ACS Applied Materials & Interfaces

Development of Liposome Systems for Enhancing the PK Properties of Bivalent PROTACs

carbohydrates, drug delivery,

Proteolysis-Targeting Chimeras (PROTACs) are a promising new technology in drug development. They have rapidly evolved in recent years, with several of them in clinical trials. While most of these advances have been associated with monovalent protein degraders, bivalent PROTACs have also entered clinical trials, although progression to market has been limited. One of the reasons is the complex physicochemical properties of the heterobifunctional PROTACs. A promising strategy to improve pharmacokinetics of highly lipophilic compounds, such as PROTACs, is encapsulation in liposome systems. Here liposome systems for intravenous administration to enhance the PK properties of two bivalent PROTAC molecules are described, by reducing clearance and increasing systemic coverage. A PROTAC-in-cyclodextrin liposome system was developed where the drug was retained in the liposome core. In PK studies at 1 mg/kg for GNE-01 the PROTAC-in-cyclodextrin liposome, compared to the solution formulation, showed a 80- and a 380-fold enhancement in AUC for mouse and rat studies, respectively. We further investigated the same PROTAC-in-cyclodextrin liposome system with the second PROTAC (GNE-02), where we monitored both lipid and drug concentrations in vivo. Similarly, in a mouse PK study of GEN-02, the PROTAC-in-cyclodextrin liposome system exhibited enhancement in plasma concentration of a 23× increase over the conventional solution formulation. Importantly, the lipid CL correlated with the drug CL. Additionally, we investigated a conventional liposome approach for GNE-02, where the PROTAC resides in the lipid bilayer. Here, a 5× increase in AUC was observed, compared to the conventional solution formulation, and the drug CL was faster than the lipid CL. These results indicate that the different liposome systems can be tailored to translate across multiple PROTAC systems to modulate and improve plasma concentrations. Optimization of the liposomes could further improve tumor concentration and improve the overall therapeutic index (TI). This delivery technology may be well suited to bring novel protein targeted PROTACs into clinics.
This is a unique industrial collaboration between Genentech, Arvinas & Bristol Myers Squibb.
#cyclodextrin #liposome #drugdelivery

Pharmaceutics | Free Full-Text | Development of Liposome Systems for Enhancing the PK Properties of Bivalent PROTACs (mdpi.com)