Succinyl Chitosan in Oral, Injectable, And Local Drug Delivery Systems

Modern drug delivery systems aim to improve therapeutic efficacy while reducing side effects and dosing frequency. However, traditional dosage forms often fail to maintain stable drug levels. Succinyl chitosan, a chemically modified chitosan derivative, has gained attention as an advanced drug carrier due to its excellent biocompatibility, biodegradability, and enhanced water solubility. Its amphoteric nature and tunable physicochemical properties make it highly suitable for oral sustained-release, long-acting injectable, and localized drug delivery systems, enabling controlled, stable, and site-specific drug release across multiple pharmaceutical applications.

What Is Succinyl Chitosan?

Succinyl chitosan is an acylated chitosan derivative obtained by introducing succinyl groups into the molecular backbone of chitosan. Chitosan itself is derived from chitin, a naturally abundant polysaccharide found in the exoskeletons of marine organisms such as shrimp and crabs. While chitosan is well known for its biodegradability, biocompatibility, and bioactivity, its limited solubility in water and neutral environments significantly restricts its pharmaceutical use.

The succinylation process introduces carboxyl groups (–COOH) into the polymer chain, transforming chitosan into an amphoteric polyelectrolyte containing both amino and carboxyl functionalities. This modification dramatically improves water solubility across a wide pH range, enhances molecular flexibility, and allows more predictable interactions with drugs and biological environments.

Importantly, succinyl chitosan retains the favorable biological properties of native chitosan, including low toxicity, enzymatic degradability, and affinity for biological tissues. These combined characteristics form the foundation for its broad applicability in advanced drug delivery systems.

Key Properties Supporting Drug Delivery Applications

Several intrinsic properties make succinyl chitosan particularly suitable for pharmaceutical formulations:

• Excellent water solubility under physiological and neutral pH conditions

• Amphoteric charge behavior, enabling pH-responsive drug release

• Strong drug–polymer interactions, improving drug stability and dispersion

• Biodegradability, reducing long-term accumulation risks

• Good bioadhesion, enhancing residence time at target sites

• Formulation versatility, supporting multiple dosage forms

These features allow succinyl chitosan to function effectively across different administration routes while maintaining safety and performance.

Role of Succinyl Chitosan in Oral Drug Delivery Systems

Challenges in Oral Drug Delivery

Oral administration remains the most widely used and patient-preferred route for drug delivery due to its convenience, safety, and cost-effectiveness. Despite these advantages, oral drug delivery presents numerous formulation challenges that can significantly limit therapeutic performance. One of the primary issues is the complex and dynamic gastrointestinal (GI) environment, which includes fluctuating pH levels, digestive enzymes, varying transit times, and the presence of food components.

Many active pharmaceutical ingredients (APIs), particularly newly developed compounds, exhibit poor aqueous solubility, leading to low dissolution rates and inconsistent absorption. In addition, enzymatic degradation and chemical instability in the GI tract can reduce the amount of active drug reaching systemic circulation. Conventional immediate-release formulations often result in rapid drug absorption followed by sharp declines in plasma concentration, which may cause suboptimal efficacy, frequent dosing requirements, and increased risk of side effects.

To address these limitations, oral sustained-release and controlled-release systems have become essential in modern pharmaceutical development. These systems aim to maintain therapeutic drug levels over extended periods while minimizing dosing frequency. However, achieving predictable oral drug release requires carrier materials that can remain stable across different GI conditions, regulate drug diffusion, and protect APIs from premature degradation.

Advantages of Succinyl Chitosan in Oral Delivery

Succinyl chitosan is particularly well suited for oral drug delivery because it effectively overcomes many of the intrinsic limitations associated with conventional polymers and native chitosan. Its pH-independent solubility is one of its most important advantages. Unlike native chitosan, which dissolves only under acidic conditions, succinyl chitosan remains soluble and stable throughout the pH variations of the gastrointestinal tract, from the stomach to the intestine.

When incorporated into tablets, capsules, microparticles, or nanoparticles, succinyl chitosan forms hydrated polymer matrices that regulate drug release through diffusion and polymer relaxation mechanisms. This controlled swelling behavior allows drugs to be released gradually rather than all at once, resulting in smoother plasma concentration–time profiles and prolonged therapeutic effects.

In addition to release control, succinyl chitosan enhances drug stability by reducing crystallization and aggregation of APIs within the formulation. It also provides a protective microenvironment that shields drugs from enzymatic or chemical degradation in the GI tract. Furthermore, its inherent bioadhesive properties increase residence time at the intestinal mucosa, which can significantly improve drug absorption and overall bioavailability.

Typical Oral Dosage Forms Based on Succinyl Chitosan

Thanks to its tunable molecular weight and adjustable degree of succinylation, succinyl chitosan can be tailored to a wide range of oral dosage forms, including sustained-release tablets and capsules, polymer-coated pellets, microparticles, nanoparticles, and oral mucoadhesive systems. By fine-tuning these parameters, formulation scientists can precisely control drug release kinetics and adapt formulations to different therapeutic requirements.

Applications in Injectable Drug Delivery Systems

Need for Long-Acting Injectable Formulations

Injectable drug delivery systems play a crucial role in therapies requiring rapid onset, high bioavailability, or precise dosing. In recent years, long-acting injectable formulations have attracted growing interest, particularly for chronic diseases, hormone therapies, and biologics. These formulations reduce dosing frequency, improve patient adherence, and provide more consistent therapeutic outcomes.

However, developing injectable systems capable of sustained drug release without inducing toxicity, inflammation, or tissue irritation remains challenging. Ideal injectable carriers must be biocompatible, biodegradable, injectable under mild conditions, and capable of forming stable drug depots after administration.

Succinyl Chitosan-Based Injectable Systems

Succinyl chitosan meets these requirements exceptionally well. It can be formulated into injectable hydrogels, microspheres, and nanoparticles that form localized depots at the injection site. Once administered, these systems release drugs gradually through a combination of diffusion-controlled transport and polymer degradation.

Because succinyl chitosan is biodegradable, it breaks down into non-toxic byproducts over time, minimizing the risk of long-term tissue accumulation. Its amphoteric structure also allows it to respond to local physiological conditions, further regulating drug release behavior and enhancing formulation predictability.

Benefits in Injectable Applications

In injectable drug delivery, succinyl chitosan offers multiple advantages, including reduced injection frequency, improved patient compliance, sustained and predictable drug release profiles, and a high safety margin for long-term use. These benefits make it an attractive material for injectable therapies that require prolonged drug exposure and reliable performance.

Local and Site-Specific Drug Delivery Applications

Importance of Localized Drug Delivery

Local and site-specific drug delivery focuses on delivering therapeutic agents directly to the target tissue, thereby maximizing local efficacy while minimizing systemic exposure and side effects. This strategy is particularly valuable in mucosal, ocular, dermal, and wound-related applications, where prolonged contact with the target site is essential for therapeutic success.

Effective local drug delivery systems must adhere to biological surfaces, maintain sufficient drug concentration at the site of action, and release drugs in a controlled manner over time.

Bioadhesive Properties of Succinyl Chitosan

Succinyl chitosan exhibits strong bioadhesive behavior due to the presence of amino and carboxyl functional groups that interact with mucosal and tissue surfaces through hydrogen bonding and electrostatic interactions. This bioadhesion significantly enhances drug retention and prolongs residence time at the application site.

As a result, succinyl chitosan is widely used in nasal, oral, ocular, vaginal, and dermal drug delivery systems. By supporting sustained local drug release while limiting systemic absorption, it improves therapeutic efficiency and reduces unwanted side effects.

Common Local Delivery Formats

Succinyl chitosan is commonly formulated into mucoadhesive gels and films, wound dressings and topical formulations, ocular inserts and eye drops, as well as transdermal and intranasal delivery systems. These formats benefit from its excellent film-forming ability, moisture retention, and controlled release characteristics, making it a versatile material for localized pharmaceutical applications.

Mechanisms of Drug Release Across Different Routes

Succinyl chitosan enables controlled and sustained drug delivery through multiple complementary mechanisms:

These mechanisms work synergistically to ensure predictable drug release profiles across oral, injectable, and local delivery systems.

Comparison With Native Chitosan in Drug Delivery

This comparison highlights why succinyl chitosan is increasingly preferred over native chitosan in advanced drug delivery applications.

Conclusion

Succinyl chitosan has proven to be a versatile and reliable biomaterial for oral, injectable, and local drug delivery systems. Its excellent solubility, amphoteric structure, biodegradability, and adjustable release behavior effectively meet the demands of modern controlled and sustained drug delivery. With a strong safety profile and broad formulation flexibility, succinyl chitosan continues to gain importance in pharmaceutical development. For deeper technical insights, customized solutions, or application support, readers are encouraged to explore further information and professional guidance from Jinan Xinzhiyuan Biotechnology Co., Ltd., a trusted supplier in advanced chitosan derivatives.

FAQ

1. Why is succinyl chitosan used instead of native chitosan in drug delivery?
Because it offers better water solubility, wider pH stability, and more reliable controlled drug release.

2. How does succinyl chitosan improve oral drug delivery?
It stays stable in the GI tract and enables sustained drug release with improved absorption.

3. Is succinyl chitosan suitable for injectable formulations?
Yes, it is biocompatible, biodegradable, and supports long-acting injectable drug release.

4. What role does succinyl chitosan play in local drug delivery?
Its bioadhesive properties prolong drug retention and enhance local therapeutic effects.