ALGINATE : THE BIOPOLYMER OF FUTURE FOR THE OCULAR DRUG DELIVERY SYSTEM

 Abstract

One of the most susceptible and vital organs in our body is the eye, but due to various ocular barriers like tear turnover, nasolacrimal drainage, blood retinal barriers etc. possess a great challenge for the ocular delivery of drugs. Alginate, a natural polysaccharide obtained from marine brown seaweeds and various bacterial sources carries a great potential for the novel ocular drug delivery formulations. Alginate which is already a renowned excipient in other fields of drug delivery and due to its various advantages like mucoadhesive behaviour, biodegradable and non-toxic nature makes it a perfect candidate for this delivery route. The ability of instant gelation results into higher ocular residence time and enhanced ocular drug bioavailability which means lower frequency of ocular drug administration. The various alginate based ocular drug delivery formulations include in situ gels, microparticles, nanoparticles, ocular films, ocular inserts, ocular gels and biodegradable nanosheets which are capable of successfully deliver various categories of drugs like antibiotic, antifungal, anti-glaucoma, anti-hypertensive, NSAID and anticancer. So, due to the various unique properties of the alginate, the pharmaceutical scientists possess a great interest to explore the new angle in the ocular drug delivery using this biopolymer.

Introduction 

Developing successful ocular drug delivery systems faces challenges due to barriers & quick washout. Alginate, a widely used biopolymer, offers promise. Its Ca2+ ion sensitive gelation behaviour increases ocular residence time & bioavailability. Various strategies, including in situ gels, nanoparticles, and ocular inserts, utilize alginate for targeted drug delivery. Recent studies highlight alginate's effectiveness in prolonging ocular residence time. Despite regulatory disparities, alginate's biodegradability and biocompatibility make it appealing. Chemical modifications and a deeper understanding of alginate’s will enhance therapeutic efficacy and patient compliance.

ALGINATE 

Alginate, a natural polysaccharide from marine sources, holds promise for innovative ocular drug delivery. Alginates are the salts of alginic acid and its various derivatives. It is a type of linear polysaccharide which is distributed widely throughout the cell walls of the brown algae. Alginate's gel-forming ability extends drug residence time, enhancing bioavailability and reducing administration frequency.

DIFFERENT ALGINATE BASED OCULAR DRUG DELIVERY SYSTEM

                                 

IN SITU GEL : An in situ gelling system, refers to a type of solution with low viscosity that transforms into a gel when exposed to specific stimuli like temperature, pH changes. This approach offers various benefits, including improved ocular retention and increased bioavailability.

NANOPARTICLES : Nanoparticles, such as polymeric nanoparticles, liposomes, and lipid-based nanocarriers. These include low toxicity, long-term stability, simple production methods, and extended residence time.

MICROPARTICLES : This became a promising candidate, due to its easy synthesis, higher drug encapsulation & sustained drug release pattern.

OCULAR FILMS : Ocular films are specialized drug delivery systems designed to be placed within the cul-de-sac of the eye. This method offers extended contact time with the eye's surface, enabling precise drug dosing and reducing the risk of systemic side effects.

OCULAR INSERTS : Ocular inserts are sterile, multilayer formulations containing solid or semisolid drugs for eye delivery, offering extended contact with conjunctival tissue and sustained drug release, reducing systemic side effects.

OCULAR GELS : Ocular gels are an innovative approach to deliver ophthalmic drugs by incorporating them into a gel system applied directly to the eye's surface. This method offers the advantage of accommodating various drugs and ensuring prolonged contact with the ocular surface for controlled drug release over an extended period.

IPN HYDROGELS : IPN hydrogels are three-dimensional networks of cross-linked polymers that store drugs within their interconnected cavities, allowing for controlled drug release with minimal side effects. The main challenge lies in their preparation technique and feasibility, but they exhibit prolonged stability due to molecular entanglements.

BIODEGRADABLE NANOSHEETS : For the synthesis of nanosheets, chitosan and sodium alginate were employed at varying proportions using layer-by-layer technique. Spin coating method was followed on SiO2 substrate at 4500 rpm. Multi-layered polymeric nanosheets were fabricated using alginate and chitosan and the latanoprost isopropyl ester was loaded into those nanosheets in different proportions.

PROPERTIES OF ALGINATE

Mucoadhesive

Biodegradable

Non-toxic

Gel-forming Ability

Enhanced Bioavailability

MECHANISM OF ACTION

                                                                     

 Alginate forms a gel-like matrix upon contact with the eye's tear fluid. This gel matrix serves as a reservoir for the drug, gradually releasing it over an extended period. The drug's release occurs through a combination of diffusion and erosion processes. Initially, the drug diffuses out of the gel matrix, reaching the eye's target tissues. Simultaneously, the alginate gel slowly erodes as it interacts with tear fluid, sustaining drug release. This controlled release mechanism ensures a prolonged therapeutic effect, reducing the need for frequent dosing and enhancing patient compliance.

 APPLICATIONS

Antibiotic Drug Delivery

Antifungal Drug Delivery

Anti-Glaucoma Drug Delivery

Anti-Hypertensive Drug Delivery

NSAID Drug Delivery.

FUTURE PERSPECTIVE

1. Alginate based 3D Cell Culture System

2. Cell based Micro Particle For Therapeutic Application

3. Biological Activity Of Alginate Oligosaccharides.

CONCLUSION

Alginate, a biopolymer, addresses ocular drug delivery challenges via Ca2+ ion-sensitive gelation, enhancing bioavailability and residence time. Strategies like in situ gels, nanoparticles, and inserts employ alginate for targeted therapy. Regulatory hurdles exist, but alginate's biocompatibility and biodegradability offer promise. Ongoing research and chemical modifications can optimize efficacy and patient compliance.

REFERENCES

Aburahma, M. H., & Mahmoud, A. A. (2011). Biodegradable ocular inserts for sustained delivery of brimonidine tartarate: Preparation and in vitro/in vivo evaluation. AAPS PharmSciTech, 12, 1335–1347.

Agrawal, A. K., Das, M., & Jain, S. (2012). In situ gel systems as ‘smart’carriers for sustained ocular drug delivery. Expert Opinion on Drug Delivery, 9, 383–402.