Complex Hydrogels Composed of Chitosan with Ring-opened Polyvinyl Pyrrolidone as a Gastroretentive Drug Dosage Form to Enhance the Bioavailability of Bisphosphonates

Abstract

Complex hydrogels formed with chitosan (CS) and ring-opened polyvinyl pyrrolidone (roPVP) as a swellable mucoadhesive gastroretentive drug dosage form (smGRDDF) were prepared and characterized. CS/roPVP hydrogels were produced by blending CS with roPVP obtained by basic treatment of PVP. Effects of the heating time and NaOH concentration employed for preparing roPVP, and CS molecular weights (Mws), and roPVP/CS ratios on the swelling ability of the resultant hydrogels were characterized. Rheological characteristics were further examined. Results demonstrated that roPVP obtained in a 0.5 M NaOH solution heated to 50 °C for 4 h was suitable for producing complex hydrogels with CS. At a roPVP/CS ratio of 20:1, hydrogels composed of three different Mws of CS possessed optimal swelling and mucoadhesive abilities and rheological properties. In vitro dissolution revealed sustained drug release. A pharmacokinetic study exhibited that the plasma profile of alendronate followed a sustained manner with 3-fold enhancement of the oral bioavailability. In conclusion, the smGRDDF composed of CS/roPVP complex hydrogels was successfully developed and is potentially applicable to improve the clinical efficacy of bisphosphonates.

Hydrogels and Their Applications in Targeted Drug Delivery

“…Enhanced muco-adhesion, delayed clearance from swelling, minimal localized irritation, improved bioavailability and slower release of the active ingredients are the interesting aspects of the preparation. Also, in vivo experimentation showed that these hydrogels could provide optimized PK properties that maintained the drug in the therapeutic levels for a sustained period of time, minimizing fluctuations in therapeutic levels, hence also the possible side effects [55].…”

Gastroretentive Technologies in Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug Bioavailability and Patient Compliance Implications

“…Swelling polymers which reduce dosage form density, such as hydroxypropylmethylcellulose (HPMC) and polyethylene oxide (PEO), are effective in achieving prolonged buoyancy and enabling floatation [45,46]. Polymers with strong mucoadhesive properties, such as Carbopol ® and chitosan, can assist gastric retention of the dosage form on the stomach wall [47,48]. In addition, other excipients that can also affect the system performance need to be considered, such as gas-generating agents for effervescent floating dosage forms and materials with swelling properties for superporous hydrogel systems.…”

“…Chitosan can form gels with improved mechanical strength through chemical cross-linking using glutaraldehyde, glyoxal or other substances as cross-linkers, or through physical cross-linking as ionically cross-linked chitosan gels with multi-valent phosphates or as polyionic complexes of positively charged chitosan with a negatively charged polymer, such as alginate or polylactic acid. Chitosan-based hydrogels have been used for mucoadhesive and other gastroretentive, as well as controlled-release, applications [47,[142][143][144][145][146][147][148][149][150][151][152][153].…”

Nanomaterials for the Photothermal Killing of Bacteria

“…Hydrogels present multiple advantages for wound dressings, such as oxygenation, water permeability, the preservation of a moist microenvironment, etc. [ 79 , 80 , 81 , 82 , 83 ]. Inorganic nanomaterials such as metals [ 84 ], transition metals [ 85 ], and carbon-based nanomaterials [ 86 ] with a photothermal effect can be incorporated into hydrogels to improve the photothermal capacities.…”