Chitosan has prompted the continuous impetus for the development of safe and effective drug delivery systems because of its unique physicochemical and biological characteristics. The primary hydroxyl and amine groups located on the backbone of chitosan allow for chemical modification to control its physical properties.
PLGA has excellent biodegradability and biocompatibility and is generally recognized as safe by international regulatory agencies including the United States Food and Drug Administration and the European Medicines Agency. The physicochemical properties of PLGA may be varied systematically by changing the ratio of lactic acid to glycolic acid.
This in turn alters the release rate of microencapsulated therapeutic molecules from PLGA microparticle formulations.
In this review, we address strategies aimed at overcoming these challenges. These include use of low-temperature double-emulsion methods to increase drug-loading by producing PLGA particles with a small volume for the inner water phase and a suitable pH of the external phase.
Newer strategies for producing PLGA particles with high drug loading and the desired sustained-release profiles include fabrication of multi-layered microparticles, nanoparticles-in-microparticles, use of hydrogel templates, as well as coaxial electrospray, microfluidics, and supercritical carbon dioxide methods.
Another recent strategy with promise for producing particles with well-controlled and reproducible sustained-release profiles involves complexation of PLGA with additives such as polyethylene glycol, poly ortho esterschitosan, alginate, caffeic acid, hyaluronic acid, and silicon dioxide.
Introduction Drug delivery systems with high efficiency and tuneable release characteristics continue to be sought. This is despite recent advances in the field of nanobiotechnology that have produced a range of new materials for improving control over drug delivery rates Hillery et al.
The strategies used to produce these sustained-release dosage forms involve drug loading of biodegradable polymeric microspheres and have the potential to provide a more facile route to adjust release rates Kapoor et al. Poly lactic-co-glycolic acid PLGAis a widely used biodegradable material use for encapsulation of a broad range of therapeutic agents including hydrophilic and hydrophobic small molecule drugs, DNA, proteins, and the like Zheng, ; Malavia et al.
Complete release of encapsulated molecules is achieved via degradation and erosion of the polymer matrix Anderson and Shive,; Fredenberg et al. In the following sections, we review strategies and new technologies with promise for addressing these issues.
Challenges in Improving Drug Loading of Microparticles with Acceptable Control Over Release Rate Profiles Physicochemical Properties of the Incorporated Drug s Achieving the desired loading of low molecular weight Mrhydrophilic molecules in polymeric particles is more difficult than for hydrophobic small molecules, despite the large number of micro-encapsulation methods described in peer-reviewed publications and patents Ito et al.
Manipulation of the physicochemical properties is often the most effective means for optimizing drug loading into PLGA microspheres Curley et al. For example, small molecules that are hydrophilic in their salt form can be converted to the corresponding free acid or free base forms that are more hydrophobic, subsequently leading to higher drug loading Han et al.
The physicochemical properties of the incorporated drug s also significantly affect release rate profiles Hillery et al. These parameters are influenced by the physicochemical properties of the drug, such as molecular size, hydrophilicity, and charge Hillery et al.
A relatively high content of a water-soluble drug facilitates water penetration into particles and formation of a highly porous polymer network upon drug leaching Feng et al. By contrast, hydrophobic drugs can hinder water diffusion into microparticulate systems and reduce the rate of polymer degradation Klose et al.
This is illustrated by observations that for six drugs with diverse chemical structures, viz.
Hence, the design of biodegradable polymeric carriers with high drug loading must take into consideration the effects of the encapsulated drug itself on the mechanisms underpinning biopolymer degradation that influence release rate Siegel et al.
Particle Size Key factors in the design of microparticle drug delivery systems include microsphere size and morphology Langer et al. For large diameter particles, the small surface area per unit volume leads to a reduced rate of water permeation and matrix degradation relative to smaller particles and so the maximum possible rate of encapsulated drug release is reduced Dawes et al.
For drugs microencapsulated in larger microparticles, duration of action is potentially longer due to higher total drug loading and a longer particle degradation time Klose et al. Hence, a good understanding of the relationship between biopolymer composition, microparticle morphology and size is essential for tailored production of particulate materials with pre-determined drug release profiles Cai et al.
However, based upon the diversity of encapsulated drug release profiles produced by PLGA microspheres of varying sizes to date Table 1release rates do not necessarily conform to predicted behavior and it is only possible to quantitatively predict the effect of microparticle size on drug release kinetics for certain well-defined formulations Siepmann et al.
Influence of particle size, polymer physicochemical properties as well as PLGA composition on drug loading and release profiles.
In the first phase, there is a rapid decrease in molecular weight Mr but little mass loss whereas in the second phase, the opposite occurs.Chitosan based micro particulate systems are used for the delivery of local anaesthetic drugs. Chitosan, which is abbreviated as (CS) is a polysaccharide.
Chitosan is obtained from chitin, which is abundantly available in the skeleton of marine crustaceans.
CHITOSAN BASED MICROPARTICULATE SYSTEMS FOR THE DELIVERY OF LOCAL ANAESTHETIC. Introduction: Chitosan based micro particulate systems are used for the delivery of local anaesthetic drugs.
Chitosan, which is abbreviated as (CS) is a polysaccharide. Chitosan is obtained from chitin, which is abundantly available in the skeleton of marine crustaceans.
The potential of chitosan in drug delivery has stimulated extensive research in nanoparticulate systems of chitosan. The fabrication of chitosan-based nanoparticles requires various physicochemical considerations of the polymer.
Patent application title: Hydrophilic Particles Based on Cationic Chitosan Derivatives Inventors: Peter Kauper (Lausanne, CH) Carsten Laue (Nyon, CH) A process for making hydrophilic nanoparticles consisting of one type of cationic chitosan derivative and one type of polyanionic polymer, comprising:i.
preparing an aqueous solution of said. Development of Chitosan‑based Dry Powder Inhalation System of Cisplatin for Lung Cancer D. J.
SINGH, A. A. LOHADE, J. J. PARMAR, DARSHANA D. HEGDE, cisplatin microparticulate systems, which helps to localize the drug in the lungs, and also provide sustained action. Chitosan (2-aminodeoxy-β Miyazaki S, Nakayama A, Oda M, Takada M, Attwood D.
Chitosan and sodium alginate based bioadhesive tablets for intraoral drug delivery. Biol Pharm Bull. ; – Chitosan: properties, preparations and application to microparticulate systems. J Microencapsul. ; –