Amino Acids for Sustained-Release Injectables

Amino acids are a crucial class of biomolecules, and their unique chemical structures and biological functions play a significant role in drug development. In recent years, with the continuous advancement of sustained-release formulation technologies, amino acids have demonstrated broad potential as key components in the development and application of sustained-release injectables. These formulations leverage the multifunctional properties of amino acids to optimize drug release rates, enhance drug stability, and reduce adverse effects.

What is Sustained Release?

Sustained release (SR) is a form of delivery that enables a drug to be delivered over a longer period of time with fairly stable drug concentrations in the bloodstream or body's tissues. This release mechanism is not the same as in standard immediate-release medication wherein the drug is absorbed very quickly. Continuous release systems aim to reduce dosing, make patients more compliant, and maximise the effectiveness and safety of a drug. Sustained-release technology usually needs advanced formulation or delivery system, including sustained-release tablets, capsules, injectables or implants. These mechanisms manage drug release rate so that pharmacokinetic fluctuations, side-effects of overdose and underperforming efficacy at low doses can be minimized.

Fig. 1. Sustained release medication.

Sustained Release vs Extended Release

Sustained release (SR) and extended release (ER) are two common concepts in modern drug delivery systems. While they share similarities, they also exhibit significant differences:

Sustained-Release Injectables

Sustained-release injectables are drug formulations designed to achieve sustained-release effects through injection. These formulations use specialized delivery systems, such as microspheres, nanoparticles, liposomes, or implants, to release the drug slowly into the body. Injectable sustained-release products are intended to serve as a drug reservoir, which can include subcutaneous, intramuscular, or local injections. Local injection formulations release the drug at specific target sites, such as the brain/spinal cord, joints, or eyes, and can target areas like tumors, infection/inflammation/pain sites, or other potentially affected areas. Whether a drug is suitable for a sustained-release system depends on several factors: 1) the drug must have a sufficiently long half-life to achieve a feasible dosing regimen; 2) the drug must be released at a sufficient therapeutic rate over the entire duration of action, ensuring effective treatment without depending on the drug's trough concentration between doses. Below are some examples of sustained/controlled-release formulations used or considered in clinical trials across therapeutic areas:

1. Local administration for the treatment of various cancers, viral infections (such as cytomegalovirus), and other infectious diseases.
2. Relief of localized pain, such as arthritis—prolonged duration of action is particularly needed when the injection itself is painful or difficult to administer.
3. Relief of other types of pain. When prolonging pain relief, the effectiveness of anesthetic painkillers should be compared through different administration routes, such as sustained-release formulations versus free form administration.
4. When administering sustained-release local anesthetic formulations, the duration of pain relief in the targeted area is extended.
5. Treatment of localized tissue infections.
6. Local treatment for bone regeneration, such as bone regeneration/healing after severe trauma.
7. Slow drug release into the systemic circulation to extend the duration of action, such as sustained-release formulations of antipsychotic drugs, insulin, and other hormonal treatments.

Advantages of Injectable Sustained-Release Formulations

One important reason for designing sustained-release drug formulations is to optimize pharmacokinetics, improving the drug's effectiveness while reducing its toxicity. One goal is to extend the drug's duration of action as much as possible or to achieve the desired prolonged effect. Another goal is to avoid excessively high local tissue or plasma drug concentrations immediately after administration, which could lead to potential toxicity. Typically, after oral administration of a tablet, the first-pass effect occurs, and as the drug reaches systemic circulation, its concentration peaks. If extended duration of action is needed, the peak concentration must be quite high. This initially high peak usually indicates that the patient has taken an overdose, which should be reduced, especially for drugs with high toxicity. Many oral sustained-release formulations can avoid this initial high peak because the drug is released slowly from the delivery system and maintains a therapeutic dose for a longer period. By controlling the infusion or subcutaneous injection rate, the same advantages as sustained-release formulations can be achieved, but new issues arise, such as the need for the needle and infusion tubing to remain in place during intravenous administration. However, oral sustained-release formulations cannot be applied to protein or peptide drugs. Injectable sustained-release formulations offer several distinct advantages:

• Targeted Delivery: Directly deliver drugs to the desired treatment site, reducing systemic toxicity and enhancing therapeutic efficacy. For example, corticosteroids can be injected into painful joints, or drugs can be administered directly to infection sites, such as intraocular injections.
• Localized Activity: Drugs with activity confined to specific areas, such as local anesthetics or pain relievers, can reduce or eliminate the need for systemic administration.
• Reduced Administration Frequency: Decreases the number of doses required without compromising therapeutic outcomes.
• Improved Patient Compliance: Particularly important when effective treatment requires multiple doses. Frequent dosing or challenges in swallowing pills can hinder adherence, and non-compliance often translates to suboptimal treatment outcomes.
• Cost-Effectiveness: From a pharmacoeconomic perspective, sustained-release formulations can be advantageous. Considering the costs associated with medical visits, and the time spent by doctors and nurses, sustained-release formulations can significantly reduce overall treatment expenses.
• Intellectual Property and Market Differentiation: Developing sustained-release systems allows for additional patent applications and greater market appeal.

Amino Acids in Sustained-Release Injectables

Amino acids have demonstrated significant potential in the pharmaceutical industry in various capacities. They can be used as standalone nutritional supplements, synthesized into other products, or incorporated into drug delivery systems. Amino acids play a critical role in the development and functionality of sustained-release injectables by contributing to matrix formulation, suspension, drug diffusion, and biocompatibility. Specific amino acids or combinations can be utilized to achieve targeted therapeutic goals, depending on factors such as the drug being delivered, desired release kinetics, and overall compatibility of the formulation. The inclusion of amino acids in sustained-release injectables supports the following functions:

• Regulating Solubility: Amino acids' polarity and hydrophilicity, influenced by their side chain properties, modulate drug solubility and diffusion in sustained-release systems. For example, arginine and lysine, which are positively charged, enhance the solubility of water-soluble drugs. Meanwhile, hydrophobic amino acids like valine and isoleucine are suited for controlling the release of hydrophobic drugs.
• Providing Stability: Certain amino acids reduce drug degradation through antioxidant effects or metal ion chelation. For instance, histidine stabilizes protein drugs by mitigating oxidative stress.
• pH Buffering: Due to their zwitterionic nature, amino acids serve as natural buffers, maintaining a stable drug release environment, particularly in protein and peptide-based sustained-release systems.
• Acting as Solubilizers: Some amino acids improve drug solubility by forming co-crystals or complexes. For example, glutamine enhances the solubility of anticancer drugs, facilitating smoother drug release profiles.
• Serving as Sustained-Release Matrices: Peptide-based amino acids form hydrogels through polymerization or cross-linking, acting as sustained-release matrices. Gelatin-based sustained-release injectables leverage the network structure of amino acids to control drug release rates.
• Acting as Stabilizers: Amino acids protect protein drugs from degradation. Glycine and proline are commonly used as stabilizers in lyophilized formulations, ensuring drug activity during production and storage.
• Functioning as Modifiers: Amino acids can modify drug molecules or carriers to enhance biocompatibility. For instance, PEGylation (polyethylene glycol modification) of amino acid segments can extend a drug's half-life in vivo, enabling sustained-release effects.

Amino Acid from BOC Sciences

BOC Sciences specializes in providing high-quality and diverse amino acids and their derivatives. Leveraging advanced production technologies and rigorous quality control systems, we cater to a wide range of demands, from basic amino acids to functionalized non-natural amino acids, applicable across pharmaceutical, chemical, and biotechnology industries. For the unique requirements of sustained-release injectables, we offer high-purity and stable amino acid materials suitable for diverse applications in microspheres, nanoparticles, hydrogels, and implantable injectables. Additionally, BOC Sciences provides customized amino acid synthesis solutions, including the development and optimization of amino acid derivatives, to meet the functional and release characteristic demands of complex drug delivery systems.

Amino Acids for Sustained Release Injection Delivery Systems

Amino acids are widely used in various delivery systems for sustained-release injectables due to their unique structural properties. These systems include microspheres and nanoparticles, hydrogels, liposomes, solid lipid nanoparticles, and implantable injectables. The introduction of amino acids not only optimizes the performance of these systems but also enhances the stability and efficacy of drugs while reducing side effects.

• Microspheres and Nanoparticles

Microspheres and nanoparticle systems are important forms of sustained-release injectables due to their high drug loading capacity and controlled release properties. In these systems, amino acids improve drug delivery by modulating the physicochemical properties and surface characteristics of the particles.

• Amino Acid Modification in PLGA Microspheres: Poly(lactic-co-glycolic acid) (PLGA) is a commonly used sustained-release carrier, and the addition of amino acids can further optimize its performance. For example, the introduction of hydrophobic amino acids like leucine or isoleucine enhances the hydrophobicity of microspheres, thereby slowing down drug release. This strategy is widely used in sustained-release systems for anticancer drugs, ensuring long-term stable efficacy.
• Amino Acid Enhancement in Protein Nanoparticles: Using amino acids to construct protein nanoparticles can form delivery systems with high stability and biocompatibility. For instance, the synergistic effect of serine and glycine forms stable nanoparticle structures for the slow release of antibiotics or peptide drugs, especially suitable for treating chronic infectious diseases.
• Peptide Nanoparticles: Peptide-based nanoparticles are an emerging direction for amino acid functionalization. For example, combining glutamine and arginine to encapsulate protein drugs not only improves the drug's stability but also significantly enhances the targeted delivery of drugs in the body.

• Hydrogel Systems

Amino acids provide a flexible and adjustable drug release platform for sustained-release systems by acting as crosslinkers or matrix components of hydrogels.

• Glutamic Acid-Based Hydrogels: Glutamic acid, with its rich carboxyl groups, can form three-dimensional hydrogel networks through chemical crosslinking. This structure allows for slow expansion and drug release in body fluids, and by adjusting the amino acid crosslinking density, the release rate can be precisely controlled. These hydrogels are commonly used for delivering anticancer drugs, ensuring stable and effective drug release in the tumor microenvironment.
• Histidine-Based pH-Responsive Hydrogels: The imidazole group of histidine is pH-sensitive, making it suitable for developing smart responsive hydrogels. In acidic conditions (such as the tumor microenvironment), the hydrogel rapidly degrades and releases the drug, achieving targeted drug delivery. This system has shown significant advantages in targeted cancer therapy.
• Collagen-Amino Acid Composite Hydrogels: Adding amino acids like proline to collagen-based hydrogels can enhance the mechanical strength and biodegradability of the material. This composite hydrogel is often used in local sustained-release injectables, especially in the delivery of drugs for chronic wound healing.

• Liposomes and Solid Lipid Nanoparticles

Liposomes and solid lipid nanoparticles (SLNs) are another important class of sustained-release injectable systems, with amino acids playing a vital role in stabilizing and functionalizing these carriers.

• Amino Acid Modification on Liposome Surfaces: Introducing positively charged amino acids such as lysine or arginine on the surface of liposomes can not only increase the stability of liposomes but also enhance their interaction with cell membranes, promoting drug internalization. This modification is particularly suitable for delivering antibody drugs or gene therapy drugs.
• Amino Acid Enhancement in Solid Lipid Nanoparticles: Solid lipid nanoparticles can significantly improve their drug loading and release properties by incorporating amino acid modifications. For example, using glycine-modified SLNs can reduce the risk of drug crystallization during delivery, thus improving drug bioavailability.
• Targeted Liposome Design: Connecting peptides with specific amino acid sequences, such as histidine-rich peptides, on the surface of liposomes can achieve efficient targeting of cancer cells or specific tissues. This system has shown good potential in treating diseases like breast cancer and liver cancer.

• Implantable Injectables

Implantable injectables are long-acting sustained-release systems commonly used to treat diseases that require continuous drug effects, such as hormone regulation or chronic disease management. In these systems, amino acid-modified polymer materials play a crucial role.

• Proline-Modified Polymer Carriers: Proline-modified polymer materials can be used to prepare biodegradable implants for the slow release of hormone drugs. This system can significantly extend the drug release time from weeks to months, while reducing the frequency of drug administration and improving patient compliance.
• Lysine Crosslinked Polymers: Polymers crosslinked using lysine as a crosslinker can precisely control the drug release rate. This technology is particularly suitable for sustained release of anticancer drugs, ensuring prolonged action on tumor sites without affecting healthy tissues.
• Multi-layered Amino Acid Implants: Multi-layered implants based on different amino acids can achieve multi-stage drug release. For example, the outer layer uses fast-degrading glycine-based polymers to release an initial dose, while the inner layer uses slow-degrading leucine-based polymers to maintain subsequent drug supply. This design can be used for the treatment of various chronic diseases.

** Recommended Products **

Online Inquiry

Name *

Email *

Phone *

Services & Products of Interest * Amino Acids for Sustained-Release Injectables

Project Description

Quantity *

- mg g kg ton

Verification Code *

SUBMIT