Bioengineered Amphiphilic Chitosan Nanocarriers for Improved Oral Absorption of Poorly Soluble Antihypertensive...

The clinical efficacy of many antihypertensive medications is constrained by their poor water solubility, low membrane permeability, significant first-pass metabolism, and uncertain oral bioavailability, even though hypertension is still a major worldwide health concern. For BCS Class II and IV medications like telmisartan, amlodipine, nifedipine, and carvedilol, these restrictions are especially important and call for creative delivery methods. Because of their unique dual hydrophilic-hydrophobic structure, amphiphilic chitosan derivatives have emerged as adaptable nanocarriers that may overcome these limitations. Chitosan can self-assemble into micelles, nanoparticles, nanoemulsions, and hybrid systems, with high encapsulation efficiency for lipophilic drugs when chemically modified with alkyl chains, fatty acids, bile acids, sterols, or synthetic polymer segments. By keeping medications in an amorphous, molecularly dispersed state and providing protection against gastrointestinal degradation, these nanostructures improve solubility. In addition to increasing solubility, amphiphilic chitosan improves drug permeation and systemic absorption by providing strong mucoadhesion, extended intestinal residence, and temporary modulation of tight junctions. Combined oral delivery with these carriers often results in a 2- to 3- fold increase in bioavailability and extended antihypertensive action in preclinical studies. Moreover, amphiphilic chitosan systems can provide sustained and extended release, with reduced peak-trough fluctuations and enhanced therapeutic stability. Their natural origin, biodegradability, acceptable safety profile, and regulatory acceptability strengthen their translation potential. This review carefully scrutinizes the chemistry and self-assembly processes, formulation strategies, pharmacokinetic advantages, safety-related issues, and potential uses of amphiphilic chitosan-based nanocarriers. All things considered, these technologies represent an interesting emerging delivery approach that may improve the oral bioavailability and therapeutic efficacy of poorly soluble antihypertensive drugs.