Developmentofdissolvingmicroneedleplatformforanti-obesitygenetherapy

Abstract

Obesityisagrowingpathologicalandsocialproblemworldwide.Obesitycanaffectinsulinsensitivity,whichcanleadtodiabetes.Currently,obesitytreatmentisfocusedonfatabsorptionandappetitesuppression.FABP4andFABP5areintheadiposetissue,andFABP5replacesFABP4whenFABP4islost.Therefore,inpreviousstudies,weinvestigateddoubleinhibitionbyselectivelytargetingwhiteadipocytesusinganRNAisystem,plasmid-basedsh(FABP4/5).IthasbeenconfirmedthatFABP4andFABP5shRNAeffectivelyloseweightthroughsubcutaneousandintraperitonealdeliverytosuppressinflammationandimprovelivermetabolism.Inthisstudy,thesamesubcutaneousinjectioncycleinthepreviousstudywasused(threetimesaweekforsixweeks).Obesemicelostweightduetoamicroneedle(22%).Comparedtosubcutaneousinjections,microneedlesarepainlessandthesizeofmicroneedlesissmall,sopeopleevenwithneedlephobiacaneasilyinjectthem.Dissolvingmicroneedleshavemanyadvantages.Itisbiocompatibility,largerdrugloadingcapacityinthedissolvingmicroneedles,easytobemanufactured,andthereisnoneedtoremovethemicroneedles.Whenstoredat25°Cfor2months,thesh(FABP4/5)/ATS-9Rmicroneedlecontaininghyaluronicacidwasmorestablethanthesolution.Thisresultcouldbeasolutionformicroneedle'slong-termtreatmentofobesity.Inaddition,thereductionofinflammatorycytokineswasalsoconfirmed,andtheinhibitionoffattyliverwasalsoconfirmedthroughthecontinuousreleaseofsh(FABP4/5)/ATS-9Rfrommicroneedles. Theabovestudysuggeststhatmicroneedlescontainingsh(FABP4/5)/ATS-9Rareaneffectivewaytoperformsystemictreatmentaswellaslocaltreatmentofobesityforalongtime.|비만은세계적으로증가하는병리학적,사회적문제이다.비만은당뇨병이발생할수있는인슐린민감성에영향을미칠수있다.현재비만치료는지방흡수와식욕억제에초점이맞춰져있다.FABP4,FABP5는지방조직에위치하는데,FABP4가손실됐을때FABP5는FABP4를대체한다.따라서이전연구에서는RNAi시스템중플라스미드기반sh(FABP4/5)를사용하여백색지방세포를선택적으로표적하는이중억제를조사했다.FABP4와FABP5shRNA의경피전달을통해체중을효과적으로감소시켜염증을억제하고간대사를개선하는것으로확인됐다.이번연구에서이전연구의피하주사주기로똑같이마이크로니들을6주동안주3회적용하여,비만쥐의체중이감소한것을확인하였다(22%).피하주사에비해마이크로니들은통증이없고,마이크로니들크기가작기때문에바늘공포증이있는사람도쉽게주사할수있다.용해성마이크로니들은생체적합성이우수하고,약물탑재용량이크고,제작에용이하며,마이크로니들제거할필요가없다는장점이있다.25℃에서2달동안보관하였을때,히알루론산이함유된sh(FABP4/5)/ATS-9R마이크로니들이용액상태보다안정적이었다.이결과는마이크로니들이비만의장기적인치료를위한해결책이될수있다.또한,염증성사이토카인의감소도확인하였고,마이크로니들로부터sh(FABP4/5)/ATS-9R의지속적인방출을통해,지방간의억제도확인하였다. 위연구는sh(FABP4/5)/ATS-9R이탑재된마이크로니들은오랜기간동안비만을국소적인뿐만아닌전신치료를할수있는효과적인방법임을시사한다.