Liposomes are recognized as promising and versatile drug vesicles. Compared with conventional drug delivery systems, liposomes have better properties, including site targeting, slow or controlled release, protection from degradation and removal, superior therapeutic efficacy, and lower toxicity.

Protheragen-ING specializes in providing comprehensive development services for liposomal drug delivery systems (DDSs). With our expertise and state-of-the-art facilities, we offer a range of services tailored to meet the specific needs of pharmaceutical companies, research institutes, and biotechnology companies.

Liposome as A Drug Delivery System

Liposomes are self-assembled (phospho)lipid-based drug vesicles that form bilayers (monolayers) and/or a series of concentric multiple bilayers (multilayers) that surround a central aqueous compartment. Liposomes range in size from 30 nm to the micrometer scale, with a phospholipid bilayer thickness of 4-5 nm. Based on the compartmentalized and lamellar structure, liposomes can be classified as unilamellar vesicles (ULVs), oligolamellar vesicles (OLVs), multilamellar vesicles (MLVs), and multivesicular vesicles liposomes (MVLs).

Fig. 1 (a) Structural illustration of liposome composition. (b) Classification of liposomal vesicles according to their lamellarity/compartment and particle size. (Liu P, et al. 2022)

Liposomes can be used as delivery vehicles for small-molecule drugs, proteins, nucleic acids, and imaging agents. Different routes of administration such as parenteral, pulmonary, oral, transdermal, ocular, and nasal routes have been developed to improve therapeutic efficacy and patient compliance.

Our Liposome DDS Development Services

• Formulation Development

We excel in designing liposomal formulations for a wide range of drug molecules, and optimize the encapsulation efficiency, stability, and release characteristics of liposome-based DDSs.

• Encapsulation Efficiency Studies

We conduct rigorous studies to determine the encapsulation efficiency of drug molecules within liposomes, maximize drug loading capacity, and ensure efficient drug delivery.

• Stability Assessment

Our team performs comprehensive stability assessments to evaluate the physical and chemical stability of liposomal formulations under various conditions, including temperature, pH, and storage duration.

• In Vitro Release Studies

By studying factors such as release kinetics, release mechanisms, and release rate modulation, we assist in optimizing drug release profiles for desired therapeutic outcomes.

• Surface Modification

We can use specific ligands such as antibodies, nucleic acids (e.g., aptamers), proteins (e.g., transferrin), peptides (e.g., iRGD, iNGR), small molecules (folic acid), and carbohydrates (e.g., dextran, mannan sugars, and galactose, targeting macrophages) for surface modification of liposomes.

• Cellular Uptake and Intracellular Delivery Studies

We evaluate the cellular uptake and intracellular delivery efficiency of liposomal drug formulations using relevant cell lines and models.

• Pharmacokinetic Studies

Our team conducts pharmacokinetic studies to assess the absorption, distribution, metabolism, and excretion (ADME) properties of liposome-encapsulated drugs.

• Preclinical Evaluation

We offer preclinical evaluation services to assess the safety, efficacy, and pharmacological activity of liposome-based DDSs in relevant animal models.

Manufacturing Processes for Liposomes

Fig. 2 The manufacturing processes of the marketed liposomal products. (Liu P, et al. 2022)

Commonly used manufacturing processes include thin-film hydration, ethanol injection, and double emulsification. The process usually involves:

1) Preparation of MLV or ULV depends on the choice of method.

2) Size reduction if necessary. The technique we use is extrusion and high-pressure homogenization (HPH).

3) Preparation and loading of the drug solution, this step is combined with step 1 for passive loading.

4) Buffer replacement and concentration if necessary.

5) Sterilization and filtration or aseptic processing.

6) Lyophilization and packaging, if necessary.

Our Drug-Loading Methods

• Passive Drug-Loading Approach

This method involves encapsulating the drug during the preparation of liposomes. Through covalent, ionic, electrostatic, non-covalent, or spatial interactions between the drug molecule and the lipid, the drug can be encapsulated within the internal aqueous space or embedded in the liposome bilayer.

• Active Drug-Loading Approach

This method, also known as remote drug loading, involves loading the agent after the creation of empty liposomes. A transmembrane gradient in pH or ionic concentration is the driving force that facilitates the transmembrane diffusion of the drug into the liposome core. The drug encapsulation process takes about 5 min to 30 min and high loading efficiencies (above 90%) can be achieved.

• Drug-Lipid Conjugation by Covalently Linking

Covalent attachment of drug molecules to lipids via linkers is another effective strategy for loading drugs into liposomes.

• Combinatorial approach, where a combination of passive and active loading is used.

Please contact us today to learn more. Together, let's revolutionize drug delivery to improve patient outcomes.