3.4 Kinetics of drug release
in plasma concentration-time profiles after oral administration to dogs were shown to be controllable by the bead system . This system made good use of salt formation of the polymers; however, functional groups of drug or the counterions might interact with the polymers or organic acid. After optimization of polymers and organic acid for each drug, this system is considered to be effective for the applications of taste-masking and site-specific drug delivery in the gastrointestinal tract. Cell-penetrating peptides are short peptide sequences that are capable of efficiently cellular internalization.
The amount of alkali is adjusted to give a final pH value of the gel mass less than or equal to about pH 9.0. In another embodiment, the final pH does not exceed 8.5. The film- forming polymer can then be combined with the plasticizer and solvent and then blended with the acid-insoluble gel to make a final homogeneous mixture.
Currently, DDSs targeting the tumoral low pH are still in an infant stage; more preclinical studies on the safety, stability, and manufacturability and accumulation of results from clinical studies are expected to facilitate the progress of development of these polymeric DDSs in the future. and coated with a PNIPAM layer for ion-sensitive colon drug delivery . D.
Anirudhan, T.S.; Mohan, A.M. Novel ph switchable gelatin based hydrogel for the controlled delivery of the anti cancer drug 5-fluorouracil. RSC Adv. Cevik, O.; Gidon, D.; Kizilel, S. Visible-light-induced synthesis of pH-responsive composite hydrogels for controlled delivery of the anticonvulsant drug pregabalin. Acta Biomater. Islam, A.; Yasin, T. Controlled delivery of drug from pH sensitive chitosan/poly (vinyl alcohol) blend.
The prepared hydrogels showed a higher degree of swelling and more drug release at higher pH than at low pH. The incorporation of glycerol monoglyceride in the alginate helps to prolong the drug release . Anirudhan et al. synthesized pH switchable hydrogels for colon targeted drug delivery to treat colon cancer. These hydrogels are composed of Î²-cyclodextrin grafted gelatin cross-linked with oxidized dextrin and observed the control release of an anticancer drug, 5-fluorouracil. The drug release profile studies reflected greater release in SIF, pH 7.4 than in SGF, pH 1.2. In comparison to neat drug, drug loaded hydrogels represented significantly improved cell inhibition for colon cancer cells during an in vitro cytotoxicity study .
Macromol. Jabeen, S.; Islam, A.; Ghaffar, A.; Gull, N.; Hameed, A.; Bashir, A.; Jamil, T.; Hussain, T. Development of a novel ph sensitive silane crosslinked injectable hydrogel for controlled release of neomycin sulfate. Int.
- Ion-exchange resins are insoluble polymers comprising a polystyrene backbone cross-linked with divinylbenzene and side chains of ion-active groups (Table 4).
- They observed that swelling in water was enhanced with increasing molecular weight of PEG.
- However, this behavior was less pronounced for samples with higher cross-linking degrees.
A diverse range of polymer compositions have been used to fabricate hydrogels. The compositions can be divided into natural, synthetic or combination of two classes . Natural polymers are biocompatible, non-toxic and excellent carriers of drugs, in addition to biodegradability which is the inherent advantage of natural polymers . However, natural polymer hydrogels have very weak mechanical strength. Among natural polymers, chitosan is a semi-synthetic natural polysaccharide attained from deacetylation of chitin under alkaline conditions [12-14].
Further, slow drug release, low absorption of drug or absence of therapeutic effect could be the risks for patients with achlorhydria or dosed under fed condition. Polyvinylacetal diethylaminoacetate (AEA) is another cationic polymer used in pharmaceutical industry for pH-dependent drug release. AEA has been reported to be insoluble above pH 5.8 . Microspheres of AEA containing trimebutine maleate have been prepared by a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method . The microspheres suppressed drug release at pH 6.8 but immediately released drug at pH 1.2.
The CODES using Eudragit L and Eudragit E has been shown to suppress drug release at both pH 1.2 and 6.8 but release drug specifically at pH 5.0 [41,42]. The CODES containing 5-aminosalicylic acid demonstrated high plasma drug concentration from 4 to 12 h after oral administration to dogs . As the colon arrival time of indigestive solids in fasting dogs bas been reported to be 3 h after dosing , this indicated that the CODES was able to deliver drug to the lower part of the gastrointestinal tract. The transit and disintegration of radiolabeled CODES were also investigated by gamma scintigraphy after oral dosing to healthy volunteers .
The values in Table 1 were obtained by following the methology described by Smart et al . The polymers, from up to down, have a decrease in mucoadhesiveness and in number of carboxylic groups, i.e. polycarboxylic polymers (carboxymethylcellulose and poly (acrylic acid)) have higher adhesive strength.
Poly(acrylamide-co-acrylic acid)-spirulina (AAm-AAc-Sp) hydrogels were prepared by free radical solution polymerization of the monomer acrylamide (AAm) and the comonomer acrylic acid (AAc) with N,N-methylene bisacrylamide (BAAm) as the crosslinker in the presence of spirulina (Sp), which is a microalga species. The swelling ratios of the hydrogels were followed by gravimetric measurements. Hence, swelling kinetics and diffusion parameters were determined. Furthermore, the morphological structures and mechanical behaviors of the hydrogels were investigated by scanning electron microscopy and by using a uniaxial compression machine, respectively. All the results showed that spirulina had strong influence in the pH-dependent swelling behavior, as well as on the kinetic and diffusion parameters due to its interaction with the acrylic acid units.
It is usually used in the treatment of stomach cancer, gastrointestinal tract pancreas, colon, ovarian, breast, and head . However, direct or intravenous administration of 5-FU has several side effects such as diarrhea, nausea, vomiting, soreness of the mouth, stomach pain, anemia, decrease in platelets, and white blood cells . Cardiac, hematological, neural, and dermatological toxic side effects are also severe via intravenous administration. However, oral administration using controlled release formulations significantly reduced the side effects [31, 32].