Liposome coated with low molecular weight chitosan and its potential use in ocular drug delivery

In this study liposome coated with low molecular weight chitosan (LCH) was proposed and investigated its in vitro and in vivo properties, and its potential use in ocular drug delivery was evaluated. LCH with a molecular weight of 8 kDa was prepared and coated on liposome loaded with diclofenac sodium. The LCH coating changed the liposome surface charge and slightly increased its particle size, while the drug encapsulation was not affected. After coating, the liposome displayed a prolonged in vitro drug release profile. LCH coated liposome also demonstrated an improved physicochemical stability at 25 °C in a 30-day storage period. The ocular bioadhesion property was evaluated by rabbit in vivo precorneal retention, and LCH coated liposome achieved a significantly prolonged retention compared with non-coated liposome or drug solution. The LCH coating also displayed a potential penetration enhancing effect for transcorneal delivery of the drug. In the ocular tolerance study, no irritation or toxicity was caused by continual administration of LCH coated liposome in a total period of 7 days. In conclusion, the LCH coating significantly modified the properties of liposome and brought a series of notable advantages for ocular drug delivery.     

Nanotechnology in ocular drug delivery

Despite numerous scientific efforts, 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 and ointment. These conventional dosage forms suffer from the problems of poor ocular bioavailability, because of various anatomical and pathophysiological 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 microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers and cyclodextrins in the field of ocular drug delivery and also depicts how the various upcoming of nanotechnology like nanodiagnostics, nanoimaging and nanomedicine can be utilized to explore the frontiers of ocular drug delivery and therapy.     

The promise of chitosan microspheres in drug delivery systems

Chitosan is a partially deacetylated polymer obtained from the alkaline deacetylation of chitin, which is a glucose-based, unbranched polysaccharide that occurs widely in nature as the principal component of exoskeletons of crustaceans and insects, as well as of the cell walls of some bacteria and fungi. Chitosan exhibits a variety of physicochemical and biological properties resulting in numerous applications in fields such as waste water treatment, agriculture, fabric and textiles, cosmetics, nutritional enhancement and food processing. In addition to its lack of toxicity and allergenicity, its biocompatibility, biodegradability and bioactivity make it a very attractive substance for diverse applications as a biomaterial in the pharmaceutical and medical fields. This review takes a closer look at the biomedical applications of chitosan microspheres. Based on recent research and existing products, some new and potential future approaches in this fascinating area are discussed.     

The promise of chitosan microspheres in drug delivery systems

Chitosan is a partially deacetylated polymer obtained from the alkaline deacetylation of chitin, which is a glucose-based, unbranched polysaccharide that occurs widely in nature as the principal component of exoskeletons of crustaceans and insects, as well as of the cell walls of some bacteria and fungi. Chitosan exhibits a variety of physicochemical and biological properties resulting in numerous applications in fields such as waste water treatment, agriculture, fabric and textiles, cosmetics, nutritional enhancement and food processing. In addition to its lack of toxicity and allergenicity, its biocompatibility, biodegradability and bioactivity make it a very attractive substance for diverse applications as a biomaterial in the pharmaceutical and medical fields. This review takes a closer look at the biomedical applications of chitosan microspheres. Based on recent research and existing products, some new and potential future approaches in this fascinating area are discussed.     

壳聚糖在药物缓释载体中的应用

壳聚糖是一种理化性质优良的多糖化合物。其组织相容性好,生物学活性多样,应用广泛。此文就壳聚糖在作为药物缓释载体的生物学特点,类型及研究应用方面作简要综述     

Review of ocular drug delivery

Successful treatment of eye diseases requires effective concentration of drug at the eye for sufficient period of time. Conventional ocular drug delivery including eye drops, systemic administration, ophthalmic ointments, is no longer sufficient to combat ocular diseases. This article reviews the constraints with conventional ocular therapy, and explores various novel approaches, to improve the ocular bioavailability of drugs to the anterior chamber of the eye.     

Cubosomes and other potential ocular drug delivery vehicles for macromolecular therapeutics

Introduction: Many macromolecular therapeutics designed to treat posterior segment eye diseases (PSEDs) are administered through frequent ocular injection, which can further deteriorate eye health. Due to the high frequency of injection and the high cost of the therapeutics, there is a need to develop new ways in which to deliver these therapeutics: ways which are both safer and more cost effective.

Areas covered: Using the most common PSED, age-related macular degeneration, as an example of a debilitating ocular disease, this review examines the key barriers limiting the delivery of macromolecular therapeutics to the posterior segment of the eye and defines the key requirements placed on particulate drug delivery vehicles (DDVs) to be suitable for this application. Recent developments in macromolecular drug delivery to treat this disease as well as the remaining shortcomings in its treatment are surveyed. Lastly, an emerging class of DDVs potentially suited to this application, called cubosomes, is introduced.

Expert opinion: Based on their excellent colloidal stability and high internal surface area, cubosomes hold great potential for the sustained release of therapeutics. Novel production methods and a better understanding of the mechanisms through which drug release from these particles can be controlled are two major recent developments toward successful application.     

The use of mucoadhesive polymers in ocular drug delivery

In the present update on mucoadhesive ocular dosage forms, the tremendous advances in the biochemistry of mucins, the development of new polymers, the use of drug complexes and other technological advances are discussed. This review focusses on recent literature regarding mucoadhesive liquid (viscous solutions, particulate systems), semi-solid (hydrogel, in situ gelling system) and solid dosage forms, with special attention to in vivo studies. Gel-forming minitablets and inserts made of thiomers show an interesting potential for future applications in the treatment of ocular diseases.     

Industrial perspective in ocular drug delivery

In the development of a commercial drug product, the formulator must consider various perspectives. The bioavailability of the active drug substance is often the major hurdle to overcome. In the past it has been common to add viscosity-enhancing agents or mucoadhesive polymers into formulations to improve ocular bioavailability. In addition to these conventional approaches, non-conventional technologies such as nanotechnology, microspheres and prodrugs could be considered to optimize the product. Along with bioavailability, the formulator must also consider the tolerability and stability of the final drug product. Quite often, the final formulation is the ideal compromise between the three. Authorities in different parts of the world have set strict requirements and guidelines for development and approval of drug products. In order to secure an expeditious development process and the shortest possible review and approval time, the formulator should be familiar with the current requirements and regulations.     

Cationic vectors in ocular drug delivery

Despite extensive research in the field, the major problem in the ocular drug delivery domain still is rapid precorneal drug loss and poor corneal permeability. One of the approaches recently developed is the drug incorporation into cationic submicronic vectors which exploit the negative charges present at the corneal surface for increased residence time and penetration. This review will focus on the formulation of three main representative cationic colloids developed for ophthalmic delivery: liposomes, emulsions and nanoparticles (NP). Parameters such as choice of the vector type and size, nature of the cationic molecule, pH and ionic strength of the external phase and characteristics of the encapsulated drug will be discussed with accent on the relevance of the positive charge.     

Role of metabolism in ocular drug delivery

Metabolism is one of the primary routes of drug elimination from the body. This process comprises of mechanisms, such as oxidation and conjugation, which lead to inactivation and/or elimination from hepatic, biliary, pulmonary, renal and ocular tissues. Enzymes involved in metabolism are expressed in various tissues of the body, liver being the primary site. Studies involving ocular tissues have demonstrated the expression of several metabolic enzymes such as esterases, peptidases, ketone reductases, and CYP-450's in these tissues. These enzymes play an important role in ocular homeostasis by preventing entry and/or eliminating xenobiotics from the ocular tissues. Scientists have targeted these enzymes in drug design and delivery through prodrug derivatization. The prodrugs undergo biotransformation to the parent drug by ocular enzymatic degradation. This review examines the distribution pattern of various metabolic enzymes in the ocular tissues, their physiological role and utility in targeted prodrug delivery.     

Advances and potential applications of chitosan derivatives as mucoadhesive biomaterials in modern drug delivery

Pharmaceutical technologists have been working extensively on various mucoadhesive polymeric systems to create an intimate and prolonged contact at the site of administration. Chitosan is one of the most promising polymers because of its non-toxic, polycationic biocompatible, biodegradable nature, and particularly due to its mucoadhesive and permeation enhancing properties. Due to its potential importance in controlled drug delivery applications, pharmaceutical scientists have exploited this mucoadhesive polymer. However, chitosan suffers from limited solubility at physiological pH and causes presystemic metabolism of drugs in intestinal and gastric fluids in the presence of proteolytic enzymes. These inherent drawbacks of chitosan have been overcome by forming derivatives such as carboxylated, various conjugates, thiolated, and acylated chitosan, thus providing a platform for sustained release formulations at a controlled rate, prolonged residence time, improved patient compliance by reducing dosing frequency, enhanced bioavailability and a significant improvement in therapeutic efficacy. We have explored the potential benefits of these improved chitosan derivatives in modern drug delivery.     

Biopharmaceutical considerations in topical ocular drug delivery

1. Despite the accessibility of the front of the eye, efficient delivery of drug to treat various ocular disorders is a challenge to the formulation scientist. The majority of ophthalmic medications are formulated as eye drops. Due to anatomical constraints, the volume that can be administered is limited to approximately 30 microL. This, together with the efficient clearance system that exists in the front of the eye, makes it difficult to maintain an effective pre-ocular drug concentration for a desired length of time. Various formulation strategies have been used to increase pre-ocular retention of eye drops. The most successful of these has been the inclusion of viscosity enhancing polymers, particularly those able to interact with the mucous layer on the eye surface or those that can undergo a transition from a solution to a gel under the conditions of the pre-ocular area. 2. When the target site is intra-ocular, drug must be absorbed from the pre-ocular region into the eye. The main route for absorption is across the cornea. However, absorption of drug across the cornea is inefficient due to its impermeable nature and small surface area. Thus, the intra-ocular bioavailability of topically administered medications is typically less than 10%. 3. Corneal permeability favours moderately lipophilic compounds. These compounds often have a low aqueous solubility. Problems in ocular drug delivery and formulation are compounded for poorly soluble drugs that must be formulated as suspensions. 4. Reformulation of ophthalmic suspensions as solutions has many advantages. This may be achieved by complexation using cyclodextrins. Solubilization using cyclodextrins can overcome many of the formulation problems. However, it is unclear as to their potential for improving ocular bioavailability, which is seemingly drug dependent and may be influenced by both the physicochemical properties of the drug and the complex formed.     

Gelatin-based particulate systems in ocular drug delivery

Despite all scientists efforts exerted over the past years, the ocular delivery of drugs remains a great challenge due to several barriers and hurdles faced by this kind of administration. The exploitation of gelatin that has a long history of safe use in pharmaceuticals and which is considered as a GRAS (Generally Regarded As Safe) material by the FDA was not fully achieved in this field. This review summarizes the recent studies and findings where gelatin-based micro- and nanoparticles were used for successful ocular delivery aiming at drawing the attention of researchers and scientists to this valuable biomaterial that has not been fully explored.     

壳聚糖在靶向制剂中的应用进展

壳聚糖是一种天然高分子化合物，壳聚糖及其衍生物具有优良的生物相容性和生物可降解性，在制药业有广阔的应用前景。综述了近几年来壳聚糖及其衍生物在靶向制剂中的应用。     

Limits on optimizing ocular drug delivery

The problem of optimizing ocular bioavailability of topically applied ophthalmic drugs is discussed. A formula for drug concentration in the tear film is derived using well-known pharmacokinetic relationships and a first-order drug decay model for the tear film. The time integral of the tear film concentration is then related to ocular bioavailability. The results of this analysis show that: (1) high corneal permeability (corresponding to lipophilic compounds) produces the highest bioavailability; (2) the bioavailability of drugs with high corneal permeability is relatively unaffected by drug volume; and (3) by making the dosage volume sufficiently small, a bioavailability improvement factor of approximately 4 can be obtained for drugs with low corneal permeability.