In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/proteins is mainly limited in parenteral approach. Oral therapy which was hampered by harsh gastrointestinal environment and poorly penetrating epithelial barriers often results in low bioavailability(less than 1%–2%). Therefore, delivery systems that are rationally designed to overcome these challenges in gastrointestinal tract and ameliorate the oral bioavailability of therapeutic peptides/proteins are seriously promising. In this review, we summarized various multifunctional delivery systems, including lipid-based particles, polysaccharide-based particles, inorganic particles, and synthetic multifunctional particles that achieved effective oral delivery of therapeutic peptides/proteins.
Ying HanZhonggao GaoLiqing ChenLin KangWei HuangMingji JinQiming WangYou Han Bae
The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells,which is usually caused by abnormal gene expression.RNA interference mediated by si RNA and mi RNA can selectively knock down the carcinogenic genes by targeting specific m RNAs.Therefore,combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy.Due to poor stability and solubility associated with gene agents and drugs,suitable protective carriers are needed and have been widely researched for the co-delivery.In this review,we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents,as well as the advances in co-delivery systems.
Lin KangZhonggao GaoWei HuangMingji JinQiming Wang
Dichloro（1,2-diaminocyclohexane）platinum（ll） （DACHPt）, a cisplatin （CDDP） analog, has shown lower toxicity than CDDP and no cross-resistance with CDDP in many CDDP-resistant cancers. PEGylated hyaluronan （mPEG-HA） is an mPEG conjugated with hyaluronan biodegradable polymer which is a naturally occurring biopolymer in the interstitium, is primarily cleared by the lymphatic system, mPEG- hyaluronan-DACHPt （PEG-HA-Pt） conjugate could circulate long-term in the bloodstream and increase DACHPt concentration in the tumor site and decrease systemic toxicity, mPEG-HA conjugates with the range of 1%-5% substitution were synthesized, and the structures were confirmed by 1H NMR and IR. The particle size of DACHPt incorporated with mPEG-HA was about 86 nm and the loading content and efficiency were about 19% （w/w） and 86%, respectively. The synthesized mPEG-HA with different PEG substitution degrees presented non toxicity, and the cell viability of DACHPt loaded in mPEG-HA nanoparticles increased with increasing doses of DACHPt. DACHPt release from nanoparticles slightly decreased with increasing PEG substitution degree from 1% to 5% at 37℃, pH 7.4 PBS solution. The DACHPt loaded in mPEG-HA nanoparticles significantly inhibited the growth ofA549 xenografts in nude mice when compared to the DACHPt loaded in HA nanoparticles and the control group after 4 weeks treatment （p 〈 0.01 compared with control）. The body weight change curve shows that the mice weight loss was less than 5% by treating with both DACHPt loaded in mPEG-HA and HA nanoparticles. In conclusion, a novel DACHPt loaded mPEG-HA delivery system was developed with sustained release and increased platinum concentration in the tumor.
