Nanotechnological approaches in Ophthalmic delivery systems

Efficient ocular drug delivery remains a challenge for pharmaceutical scientists. Most ocular diseases are treated by topical drug application in the form of solutions, suspensions, ointment and other drug delivery devices like inserts, implants, gelling systems, etc. These conventional and novel dosage forms suffer from the problems of poor ocular bioavailability, because of various anatomical and patho physiological barriers prevailing in the eye. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of various nanoparticulate systems like nanosuspensions, nanoparticles, dendrimers, etc. and depicts how the various upcoming of nanotechnological approaches will be utilized to explore the frontiers of ocular drug delivery and therapy for the prolongation of residence time of the device to reduce the repeated instillation. *Corresponding author, Mailing address: SL Harikumar* Director Rayat and Bahra Institute of Pharmacy, Sahauran, Mohali, Punjab. E-mail :[email protected] Article History:-----------------------Date of Submission: 11-08-2011 Date of Acceptance: 24-08-2011 Conflict of Interest: NIL Source of Support: NONE R e v i e w P a p e r C o v e r e d i n I n d e x C o p e r n i c u s w i t h I C V a l u e 4 .6 8 f o r 2 0 1 0 Int. J. Drug Dev. & Res., Oct-Dec 2011, 3 (4): 9-19 Covered in Scopus & Embase, Elsevier 9 compound with the aim to manage better drug pharmacokinetics, pharmacodynamic, nonspecific toxicity, immunogenity and biorecognition of system. Nanotechnology –based drug delivery systems, depending on their particle charge, surface properties and relative hydrophobicity, can be designed to be successfully used in overcoming retinal barriers and providing protection for the encapsulated drug, prolonging exposure by controlled release. It also has led to solution of various solubility-related problems of poorly soluble drugs and can be used to target mononuclear phagocyte system to allow regionspecific delivery and minimize side effect in other organs1 Drug delivery system based on nanotechnology with an appropriate particle size and narrow size range, ensuring low irritation, adequate bioavailability and compatibility with ocular tissues, may prove to be being the best delivery tools for pharmaceuticals treating ocular diseases, and such a system should be investigated for every suspended drug2. Materials at the nano scale could be a device or a system or, alternatively, supra molecular structure or a complex or composite. An early promoter of nanotechnology, Albert franks defined it as area of science and technology where dimensions and tolerance are in the range of 0.1 -100nm. In addition to development in other scientific disciplines, such as electronics and robotics, nanotechnology is expected to make significant advances in mainstream biomedical applications, including the areas of gene therapy, drug delivery, imaging and novel drug discovery techniques3. Challenges in Ophthalmic drug delivery systems Ocular drug delivery is one of the most interesting and challenging endeavors facing pharmaceutical scientists. The anatomy, physiology, and biochemistry of the eye provide a unique structure that restricts the entry of drug molecules at the required site of action. A suitable ocular formulation should release the drug overcoming the protective barriers of the eye without causing permanent tissue damage. For anterior-segment drug delivery, common routes of administration are topical instillation and sub-conjunctival injection, whereas for posterior segment drug delivery common routes include systemic dosing, periocular and intravitreal injections, and topical dosing4. Topical ocular administration of drugs has two different purposes: to treat superficial eye diseases, such as infections (e.g., conjunctivitis, blepharitis, keratitis sicca), and to provide intraocular treatment through the cornea for diseases such as glaucoma or uveitis. For their favorable cost advantage, the greater simplicity of formulation development and production, and the good patient acceptability, more than 90% of the marketed ophthalmic formulations are in the form of eye drops; yet these conventional systems cannot be considered optimal in the treatment of vision-threatening ocular diseases, as most of the drugs are washed from the eye by various mechanisms (lacrimation, tear dilution, and tear turnover). Moreover, the relatively impermeable corneal barrier restricts the entry of foreign substances. As a result, less than 5% of administered drug penetrates the cornea and reaches intraocular tissues. The cornea consists of three membranes: epithelium, endothelium, and inner stroma. The corneal epithelium, lipophilic in nature, acts as a selective barrier for small molecules and prevents the diffusion of macromolecules via the paracellular route. The stroma, located below the epithelium, is a highly hydrophilic layer making up 90% of the cornea.5 The corneal endothelium consists of a single layer of flattened epithelium like cells and is responsible for maintaining normal corneal hydration. Because the cornea is characterized by lipophilic and hydrophilic structures, it represents an effective barrier to the S.L Harikumar et al: Nanotechnological approaches in Ophthalmic delivery systems