Polysaccharides are abundant and constitute a prolific class of natural polymers that are biodegradable and biocompatible. Naturally, it is obtained from plant, algae, microorganisms, and animals. Plant and algal polysaccharides possess distinctive properties including tunable chemical functionality, hydrophilicity, and mechanical stability. Plant and algal polysaccharide hydrogels are easily fabricated owing to the existence of modifiable functional groups in the backbone of polysaccharides. Recently, plant and algal polysaccharide-based hydrogels received much attention in the delivery of drug molecules and in tissue regeneration applications due to their outstanding properties. This chapter deals with the history, classification, biodegradability, method of preparation, and evaluation of hydrogels, including plant and algal polysaccharide-based hydrogels. Additionally, the drug release mechanisms from hydrogels are discussed.
Hydrogels are essentially a cross-linked hydrophilic three-dimensional polymeric network able to absorb huge amount of biological fluids and water. Natural polysaccharides are endowed with several advantageous as hydrogel forming agents when compared with the polymers of synthetic origin. Natural polysaccharides offer the prospect of manipulating the properties through a wide variety of chemical modifications; besides, they are obtained from renewable natural sources such as plants, animals, and microorganisms; therefore these are economical, biocompatible, benign, and biodegradable. Natural polysaccharides have numerous unique physicochemical properties that are tunable for several drug delivery systems. In addition to these highly desirable characteristics, they have numerous health benefits such as immunomodulatory, antitumor, antimicrobial, antioxidant, antidiabetic, antiviral, and gastrointestinal protective properties. This chapter is presented with a brief description of various polysaccharides obtained from natural origin such as cellulose, pectin, chitosan, and fucoidan, including their sources, chemical structures, and ability of forming hydrogel.
Chiral polyheterocycles are one of the most frequently encountered scaffolds in natural products and in current drugs repertoire. A carbohydrate-based diversity oriented synthetic (DOS) approach has been employed for gaining access to many structurally diverse and stereochemically complex rigid polyheterocyclic molecules with multiple chiral hydroxyl groups to enhance aqueous solubility. Inexpensive chiral pool of D-Glucose has been judiciously exploited to get access of complex chiral polyheterocyclic structures using inexpensive, common achiral reagents and domino-Knoevenagel hetero-Diels-Alder (DKHDA) reaction as one of the key synthetic tools. Stereochemistry of newly generated stereocenters of polycyclic structures are unambiguously determined through NMR and X-ray crystallographic study. A chemoinformatic comparison (PCA and PMI) with 40 branded blockbuster drugs showed that newly generated polyheterocycles have good three-dimensional scaffold diversity and most of these pass the Lipinski filter of drug-likeness.
Hydrogels are polymer networks that are crosslinked. They have high affinity for water due to the presence of great number of hydrophilic groups and are prevented from dissolving due to their crosslinked chemical or physical bonds among the polymer chains, resulting in enormous swelling with high water-holding capacity. This property is utilized to deliver vast number of diverse therapeutic molecules in a controlled manner. Use of the natural polymers as base materials, particularly polysaccharides as scaffold in hydrogels, was extensively explored. Their popularity in the hydrogel preparation is due to their easy availability in highly pure form and has the functional groups for further chemical modification. Beside these, polysaccharide-based hydrogels are biocompatible, low toxic, and biodegradable. The polysaccharide can be manipulated in such a way that they become sensitive to many environmental stimuli; thus, responsive hydrogel systems are developed to deliver the loaded therapeutics in a particular environment. In the same line, advanced development is to generate a polysaccharide hydrogel in situ thus eliminating surgical implantation. The development of smart drug-delivery systems based on polysaccharide-based hydrogels relies on thorough understanding of physical and chemical characteristics of polysaccharide-based hydrogels along with several other tunable variables in the process. This chapter describes the latest developments in the preparation of various polysaccharide-based hydrogels and their distinct drug-delivery applications.
Responsive hydrogels comprise huge prospective in a variety of applications. The hydrogels change their properties in particular responses. To induce response in hydrogel system, various stimuli (chemical and physical) have been applied. Electric field, temperature, light, solvent composition, pressure, magnetic fields, and sound are used as physical stimuli. The chemical stimuli used are ions and pH. Application of responsive hydrogels has many fields, such as making chemical valves and artificial muscles, immobilization of cells and enzymes, drug delivery, biosensor, and concentrating dilute solutions in bioseparation. Although the concepts are sound, practical utility necessitates major improvements in the properties of hydrogel. The most considerable limitation of these responsive hydrogels is response time and that is too slow. As a result, fast responsive hydrogels are needed. This chapter presents an overview of the advances in the area of responsive hydrogels that have become the interest of most researchers.
A series of 4-substituted 3,4-dihydropyrimidine-2-ones (DHPM) was synthesized, characterized by IR, 1H NMR, 13C NMR and HRMS spectra. The compounds were evaluated in vitro for their antiviral activity against a broad range of DNA and RNA viruses, along with assessment for potential cytotoxicity in diverse mammalian cell lines. Compound 4m, which possesses a long lipophilic side chain, was found to be a potent and selective inhibitor of Punta Toro virus, a member of the Bunyaviridae. For Rift Valley fever virus, which is another Bunyavirus, the activity of 4m was negligible. DHPMs with a C-4 aryl moiety bearing halogen substitution (4b, 4c and 4d) were found to be cytotoxic in MT4 cells.
A new series of 3-(4-ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(4-ethylphenyl)-3H-quinazolin-4-one from 4-ethyl aniline with a variety of aldehydes and ketones. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. The compound 2-(N'-3-pentylidene-hydrazino)-3-(4-ethylphenyl)-3H-quinazolin-4-one (AS2) emerged as the most active compound of the series and was moderately more potent than the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to aspirin.
A variety of novel 2-methylthio-3-substituted-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-4(3H)-ones have been synthesized by reacting (2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)dithiocarbamic acid methyl ester (5) with a variety of amines. The starting material dithiocarbamate (5) was synthesized from 2-amino-3-carbethoxy-4,5,6,7-tetrahydrobenzo (b) thiophene (1) by a novel innovative route. The title compounds were investigated for analgesic, anti-inflammatory, ulcerogenicity index and antibacterial activities. While the test compounds exhibited significant activity, the compounds 1-methyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A1), 1-dimethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A2), 1-diethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A3) and 1-pyrrolidinyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A4) showed more potent analgesic activity and the compounds 1-dimethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A2), 1-diethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno-[2,3-d]pyrimidin-3-yl)thiourea (A3) and 1-pyrrolidinyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d] pyrimidin-3-yl)thiourea (A4) showed more potent anti-inflammatory activity than the reference standard diclofenac sodium.
A series of novel 3-cyclohexyl-2-substituted hydrazino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 3-cyclohexyl-2-hydrazino quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material, 3-cyclohexyl-2-hydrazino quinazolin-4(3H)-one, was synthesized from cyclohexyl amine. Title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic behavior. The compound 3-cyclohexyl-2-(1-methylbutylidene-hydrazino)-3H-quinazolin-4-one (4c) emerged as the most active compound of the series and is moderately more potent in its analgesic and anti-inflammatory activities compared to the reference standard diclofenac sodium. Interestingly, test compounds showed only mild ulcerogenic potential when compared to acetylsalicylic acid.
Quetiapine is a potent Serotonin and Dopamine receptor antagonist used to treat major depressive disorders. The present work describes a simple, precise and accurate HPTLC method for its estimation as bulk and in tablet dosage form. The chromatographic separation was carried out on precoated silica gel 60 F 254 aluminium plates using mixture of methanol and toluene (4:3%v/v) as mobile phase and densitometric evaluation of spots were carried out at 235nm using Camag TLC scanner - 3 with WINCAT 1.3.4 version software. The experimental parameters like band size of spot applied, chamber saturation time, solvent front migration, slit width etc were critically studied and optimum conditions were evolved. The drug was satisfactorily resolved with Rf value 0.41 ± 0.01. The accuracy and reliability of the proposed method was ascertained by evaluating various validation parameters like linearity (100-500ng/spot), precision (intra day 0.53 - 0.78, inter day 0.53-1.62), accuracy (98.87±0.2) and specificity according to ICH guide lines. The proposed method provides a faster and cost effective quality control tool for routine analysis of quetiapine as bulk drug and in tablet formulation.