Skip to content
2000
Volume 25, Issue 16
  • ISSN: 1389-5575
  • E-ISSN: 1875-5607

Abstract

Poor water solubility limits the bioavailability, absorption, and efficacy of many drugs, especially BCS class II and IV compounds. Polymeric drug conjugation (PDC) is a promising strategy to overcome these challenges by chemically linking hydrophobic drugs with hydrophilic polymers covalent or non-covalent bonds. This enhances aqueous solubility, stability, and bioavailability, leading to improved therapeutic effects and reduced adverse reactions. PDC prolongs drug circulation, ensuring consistent absorption at lower doses. This article focuses on how this strategy can address solubility issues and enhance drug delivery effectiveness, it also brings spotlight to investigate current advancements in the field of polymer drug conjugates. Following a structured approach guided by PRISMA, relevant research on polymeric conjugation strategies were identified by screening literature from PubMed, Scopus, and Google Scholar . Key polymers such as PEG, PLGA, HPMA, chitosan, and dextran were investigated for their solubility-enhancing capability. Clinical studies validate its success, making it a novel approach to addressing solubility related pharmaceutical challenges.

Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575399202250904091749
2025-09-15
2026-02-27
Loading full text...

Full text loading...

References

  1. EkladiousI. ColsonY.L. GrinstaffM.W. Polymer–drug conjugate therapeutics: Advances, insights and prospects.Nat. Rev. Drug Discov.201918427329410.1038/s41573‑018‑0005‑0 30542076
    [Google Scholar]
  2. EzikeT.C. OkpalaU.S. OnojaU.L. NwikeC.P. EzeakoE.C. OkparaO.J. OkoroaforC.C. EzeS.C. KaluO.L. OdohE.C. NwadikeU.G. OgbodoJ.O. UmehB.U. OssaiE.C. NwangumaB.C. Advances in drug delivery systems, challenges and future directions.Heliyon2023961748810.1016/j.heliyon.2023.e17488 37416680
    [Google Scholar]
  3. PandaP. KarS.S. MohapatraR. DNA polymer conjugates: Revolutionizing neurological disorder treatment through targeted drug delivery.Next Materials2025710033610.1016/j.nxmate.2024.100336
    [Google Scholar]
  4. LinQ. LiJ. AbudousalamuZ. SunY. XueM. YaoL. ChenM. Advancing ovarian cancer therapeutics: The role of targeted drug delivery systems.Int. J. Nanomedicine2024199351937010.2147/IJN.S478313 39282574
    [Google Scholar]
  5. LiL. PengX. ZhuD. ZhangJ. XiaoP. Recent progress in polymers with dynamic covalent bonds.Macromol. Chem. Phys.202322420230022410.1002/macp.202300224
    [Google Scholar]
  6. DadwalA. GargA. KumarB. NarangR.K. MishraN. Polymer-drug conjugates: Origins, progress to date, and future directions.In: Smart Polymeric Nano-Constructs in Drug Delivery.United StatesAcademic Press202322124810.1016/B978‑0‑323‑91248‑8.00015‑5
    [Google Scholar]
  7. TsungT.H. TsaiY.C. LeeH.P. ChenY.H. LuD.W. Biodegradable polymer-based drug-delivery systems for ocular diseases.Int. J. Mol. Sci.202324161297610.3390/ijms241612976 37629157
    [Google Scholar]
  8. AlossK. HamarP. Augmentation of the EPR effect by mild hyperthermia to improve nanoparticle delivery to the tumor.Biochim. Biophys. Acta2024187918910910.1016/j.bbcan.2024.189109
    [Google Scholar]
  9. KumariL. ChoudhariY. PatelP. GuptaG.D. SinghD. RosenholmJ.M. BansalK.K. KurmiB.D. Advancement in solubilization approaches: A step towards bioavailability enhancement of poorly soluble drugs.Life2023135109910.3390/life13051099 37240744
    [Google Scholar]
  10. Martin-AubertS. AvrillonK. TournierN. BordatA. TranV.L. IbrahimN. KereselidzeD. JegoB. PotironL. TsapisN. NicolasJ. BoissenotT. TruilletC. Successful repositioning of mertansine for improved chemotherapy by combining a polymer prodrug approach and PET imaging.J. Control. Release202537880381310.1016/j.jconrel.2024.12.050 39719212
    [Google Scholar]
  11. SchergerM. PilgerY.A. StickdornJ. KomforthP. SchmittS. KoynovK. RäderH.J. NuhnL. Efficient self-immolative raft end group modification for macromolecular immunodrug delivery.Biomacromolecules20232452380239110.1021/acs.biomac.3c00239 37093222
    [Google Scholar]
  12. MaW. WangX. ZhangD. MuX. Research progress of disulfide bond based tumor microenvironment targeted drug delivery system.Int. J. Nanomedicine2024197547756610.2147/IJN.S471734 39071505
    [Google Scholar]
  13. DachaniS.R. VashiA. MundadaA.B. MundadaP.A. RudrangiS.R.S. RudrangiS. TiwariR. Innovative polymers in pharmaceutical chemistry: Revolutionizing drug delivery systems.Polymer Plast. Tech. Mat.202564791193310.1080/25740881.2024.2440531
    [Google Scholar]
  14. FerradoJ.B. PerezA.A. MenegonM. VaillardV.A. GasserF. BaravalleM.E. OrtegaH.H. VaillardS.E. SantiagoL.G. PEGylation of genistein-loaded bovine serum albumin nanoparticles and its effect on in vitro cell viability and genotoxicity properties.Colloids Surf. B Biointerfaces202322211308210.1016/j.colsurfb.2022.113082 36542950
    [Google Scholar]
  15. ZhouL. LuY. LiuW. WangS. WangL. ZhengP. ZiG. LiuH. LiuW. WeiS. Drug conjugates for the treatment of lung cancer: From drug discovery to clinical practice.Exp. Hematol. Oncol.20241312610.1186/s40164‑024‑00493‑8 38429828
    [Google Scholar]
  16. YangY. WangS. MaP. JiangY. ChengK. YuY. JiangN. MiaoH. TangQ. LiuF. ZhaY. LiN. Drug conjugate-based anticancer therapy - Current status and perspectives.Cancer Lett.202355221596910.1016/j.canlet.2022.215969 36279982
    [Google Scholar]
  17. FuC. YuL. MiaoY. LiuX. YuZ. WeiM. Peptide–drug conjugates (PDCs): A novel trend of research and development on targeted therapy, hype or hope?Acta Pharm. Sin. B202313249851610.1016/j.apsb.2022.07.020 36873165
    [Google Scholar]
  18. HazarikaB. SinghV.P. Macrocyclic supramolecular biomaterials in anti-cancer therapeutics.Chin. Chem. Lett.2023341110822010.1016/j.cclet.2023.108220
    [Google Scholar]
  19. AmbreP. GuptaC. NaikI. MenonM. CoutinhoE. A review on exploring the opportunities of polymer drug conjugated systems for targeted cancer treatment.Curr. Drug Deliv.202320183010.2174/1567201819666220408095510 35400344
    [Google Scholar]
  20. ShenX. PanD. GongQ. GuZ. LuoK. Enhancing drug penetration in solid tumors via nanomedicine: Evaluation models, strategies and perspectives.Bioact. Mater.20243244547210.1016/j.bioactmat.2023.10.017 37965242
    [Google Scholar]
  21. UllahA. KhanM. ZhangY. ShafiqM. UllahM. AbbasA. XianxiangX. ChenG. DiaoY. Advancing therapeutic strategies with polymeric drug conjugates for nucleic acid delivery and treatment.Int. J. Nanomed.202525255210.2147/IJN.S429279
    [Google Scholar]
  22. MahadikN. BarronG.A. LinP.K. ThompsonC.J. Polymer–drug conjugates as nano-sized multi-targeting systems for the treatment of Alzheimer’s disease.RSC Pharmaceutics20241216118110.1039/D3PM00075C
    [Google Scholar]
  23. ĐorđevićS. MedelM. HillaertJ. MasiáE. Conejos-SánchezI. VicentM.J. Critical design strategies supporting optimized drug release from polymer–drug conjugates.Small2024204230315710.1002/smll.202303157 37752780
    [Google Scholar]
  24. PageM.J. McKenzieJ.E. BossuytP.M. BoutronI. HoffmannT.C. MulrowC.D. ShamseerL. TetzlaffJ.M. AklE.A. BrennanS.E. ChouR. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.bmj202137210.1136/bmj.n71
    [Google Scholar]
  25. SunY. ZhaoH. ShenY. WangP. From solution to surfaces: Engineering a water-soluble 1, 2-benzisothiazolin-3-one (BIT)-based antimicrobial conjugate for an antibacterial and antifouling brush-like coating.Prog. Org. Coat.202520010907710.1016/j.porgcoat.2025.109077
    [Google Scholar]
  26. MüllenK. ScherfU. Conjugated polymers: Where we come from, where we stand, and where we might go.Macromol. Chem. Phys.20232243220033710.1002/macp.202200337
    [Google Scholar]
  27. MalikA.H. HabibF. QaziM.J. GanayeeM.A. AhmadZ. YatooM.A. A short review article on conjugated polymers.J. Polym. Res.202330311510.1007/s10965‑023‑03451‑w
    [Google Scholar]
  28. OgundipeO.D. OlajubutuO. AdesinaS.K. Targeted drug conjugate systems for ovarian cancer chemotherapy.Biomed. Pharmacother.202316511515110.1016/j.biopha.2023.115151 37473683
    [Google Scholar]
  29. ChenL. SongY. DengL. LiuJ. LiuJ. JiangD. DaiX. MeiK. LiuJ. QiuN. Self-assembled stimuli-responsive adamantanamine-podophyllotoxin conjugate/β-cyclodextrins inclusion complex for enhanced solubility and anticancer activity.J. Mol. Struct.2025132414075210.1016/j.molstruc.2024.140752
    [Google Scholar]
  30. BaylissN. SchmidtB.V.K.J. Hydrophilic polymers: Current trends and visions for the future.Prog. Polym. Sci.202314710175310.1016/j.progpolymsci.2023.101753
    [Google Scholar]
  31. SharmaU. SarohaK. A review of hydrotropic solubilization techniques for enhancing the bioavailability of poorly soluble drugs.Int. J. Toxicol.2024431637110.1177/10915818231216414 37999970
    [Google Scholar]
  32. NegutI. BitaB. Polymeric micellar systems—a special emphasis on “smart” drug delivery.Pharmaceutics202315397610.3390/pharmaceutics15030976 36986837
    [Google Scholar]
  33. FarhoudiL. Maryam HosseinikhahS. Vahdat-LasemiF. SukhorukovV.N. KesharwaniP. SahebkarA. Polymeric micelles paving the Way: Recent breakthroughs in camptothecin delivery for enhanced chemotherapy.Int. J. Pharm.202465912429210.1016/j.ijpharm.2024.124292 38823466
    [Google Scholar]
  34. PhanA. MacKayJ.A. Steric stabilization of bioactive nanoparticles using elastin-like polypeptides.Adv. Drug Deliv. Rev.202420611518910.1016/j.addr.2024.115189 38281625
    [Google Scholar]
  35. AkandaM. MithuM.D.S.H. DouroumisD. Solid lipid nanoparticles: An effective lipid-based technology for cancer treatment.J. Drug Deliv. Sci. Technol.20238610470910.1016/j.jddst.2023.104709
    [Google Scholar]
  36. KaliG. HaddadzadeganS. Bernkop-SchnürchA. Cyclodextrins and derivatives in drug delivery: New developments, relevant clinical trials, and advanced products.Carbohydr. Polym.202432412150010.1016/j.carbpol.2023.121500 37985088
    [Google Scholar]
  37. ChenY. GongW. ZhangZ. ZhouJ. YuD.G. YiT. Reverse gradient distributions of drug and polymer molecules within electrospun core–shell nanofibers for sustained release.Int. J. Mol. Sci.20242517952410.3390/ijms25179524 39273471
    [Google Scholar]
  38. GowdaC.M. SharmaS. WairkarS. Advanced drug delivery systems utilizing β-lactoglobulin: An efficient protein-based drug carrier.Biopolymers202511627000510.1002/bip.70005 39912193
    [Google Scholar]
  39. BentoC. KatzM. SantosM.M.M. AfonsoC.A.M. Striving for uniformity: A review on advances and challenges to achieve uniform polyethylene glycol.Org. Process Res. Dev.202428486089010.1021/acs.oprd.3c00428 38660381
    [Google Scholar]
  40. GaoY. JoshiM. ZhaoZ. MitragotriS. PEGylated therapeutics in the clinic.Bioeng. Transl. Med.2024911060010.1002/btm2.10600 38193121
    [Google Scholar]
  41. GouP. LiuW. MaoW. TangJ. ShenY. SuiM. Self-assembling doxorubicinprodrug forming nanoparticles for cancer chemotherapy: Synthesis and anticancer study in vitro and in vivo.J. Mater. Chem. B Mater. Biol. Med.20131328429210.1039/C2TB00004K 32260752
    [Google Scholar]
  42. LiC. LiT. TianX. AnW. WangZ. HanB. TaoH. WangJ. WangX. Research progress on the PEGylation of therapeutic proteins and peptides (TPPs).Front. Pharmacol.202415135362610.3389/fphar.2024.1353626 38523641
    [Google Scholar]
  43. ZhongZ.X. LiX.Z. LiuJ.T. QinN. DuanH.Q. DuanX.C. Disulfide bond-based SN38 prodrug nanoassemblies with high drug loading and reduction-triggered drug release for pancreatic cancer therapy.Int. J. Nanomedicine2023181281129810.2147/IJN.S404848 36945256
    [Google Scholar]
  44. KhanS. JandrajupalliS.B. BusharaN.Z.A. RajaR.D.P. MirzaS. SharmaK. VermaR. KumarA. LohaniM. Targeting refractory triple-negative breast cancer with sacituzumab govitecan: A new era in precision medicine.Cells20241324212610.3390/cells13242126 39768216
    [Google Scholar]
  45. PytlíkováS. PecharM. ChytilP. StudenovskýM. PolaR. KotrchováL. KonefałR. ČtveráčkováL. LagaR. PankrácJ. GaoS. JiangB. YangK. FangJ. FilipováM. EtrychT. Highly hydrophilic methacrylamide-based copolymers as precursors for polymeric nanomedicines containing anthracyclines.Eur. Polym. J.202420511275610.1016/j.eurpolymj.2024.112756
    [Google Scholar]
  46. AroraR. MohantaM. JaiswalS. ThirugnanamA. MohantaP. An overview of polymer-based-bioresorbable drug-eluting stents.Innovat. Emerg. Tech.202411243000210.1142/S2737599424300022
    [Google Scholar]
  47. XieB. LiuY. LiX. YangP. HeW. Solubilization techniques used for poorly water-soluble drugs.Acta Pharm. Sin. B202414114683471610.1016/j.apsb.2024.08.027 39664427
    [Google Scholar]
  48. TripathiR. YadavJ.P. PathakP. AlmatarnehM.H. VermaA. Polymer–drug linking through amide bonds: The chemistry and applications in drug delivery.In: Polymer-Drug Conjugates. MadanJ. BaldiA. ChaudharyM. ChopraN. United StatesAcademic Press202314717010.1016/B978‑0‑323‑91663‑9.00007‑2
    [Google Scholar]
  49. YangJ. ZengH. LuoY. ChenY. WangM. WuC. HuP. Recent applications of plga in drug delivery systems.Polymers20241618260610.3390/polym16182606 39339068
    [Google Scholar]
  50. HuQ. ZhangY. MukerabigwiJ.F. WangH. CaoY. Polymer conjugate as the new promising drug delivery system for combination therapy against cancer.Curr. Top. Med. Chem.202424131101111910.2174/0115680266280603240321064308 39005059
    [Google Scholar]
  51. ParasharA.K. SaraogiG.K. JainP.K. KurmiB. ShrivastavaV. AroraV. Polymer-drug conjugates: Revolutionizing nanotheranostic agents for diagnosis and therapy.Discover Oncology202415164110.1007/s12672‑024‑01509‑9 39527173
    [Google Scholar]
  52. MoniS.S. MoshiJ.M. Matou-NasriS. AlotaibiS. HawsawiY.M. ElmobarkM.E. HakamiA.M.S. JeraibyM.A. SulayliA.A. MoafaH.N. Advances in materials science for precision melanoma therapy: Nanotechnology-enhanced drug delivery systems.Pharmaceutics202517329610.3390/pharmaceutics17030296 40142960
    [Google Scholar]
  53. ImantayA. MashurovN. ZhaisanbayevaB.A. MunE.A. Doxorubicin-conjugated nanoparticles for potential use as drug delivery systems.Nanomaterials202515213310.3390/nano15020133 39852748
    [Google Scholar]
  54. PetroviciA.R. PintealaM. SimionescuN. Dextran formulations as effective delivery systems of therapeutic agents.Molecules2023283108610.3390/molecules28031086
    [Google Scholar]
  55. ChellathuraiM.S. YongC.L. SofianZ.M. SahudinS. HasimN.B.M. MahmoodS. Self-assembled chitosan-insulin oral nanoparticles — A critical perspective review.Int. J. Biol. Macromol.202324312512510.1016/j.ijbiomac.2023.125125 37263321
    [Google Scholar]
  56. ŽigrayováD. MikušováV. MikušP. Advances in chitosan derivatives: Preparation, properties and applications in pharmacy and medicine.Gels2024101170110.3390/gels10110701 39590057
    [Google Scholar]
  57. AlfatamaM. ChoukaifeH. AlkhatibH. Al RahalO. ZinN.Z.M. A comprehensive review of oral chitosan drug delivery systems: Applications for oral insulin delivery.Nanotechnol. Rev.20241312023020510.1515/ntrev‑2023‑0205
    [Google Scholar]
  58. KaurK. Al-KhazalehA.K. BhuyanD.J. LiF. LiC.G. A review of recent curcumin analogues and their antioxidant, anti-inflammatory, and anticancer activities.Antioxidants2024139109210.3390/antiox13091092 39334750
    [Google Scholar]
  59. IlhanH. Nanoarchitectonics of the effects of curcumin carbon dot-decorated chitosan nanoparticles on proliferation and apoptosis-related gene expressions in HepG2 hepatocellular carcinoma cells.ACS Omega2023837335543356310.1021/acsomega.3c03405 37744806
    [Google Scholar]
  60. GrewalA.K. SalarR.K. Chitosan nanoparticle delivery systems: An effective approach to enhancing efficacy and safety of anticancer drugs.Nano TransMed2024310004010.1016/j.ntm.2024.100040
    [Google Scholar]
  61. NgeceK. NtondiniT.L. KhwazaV. PacaA.M. AderibigbeB.A. Polyene-based derivatives with antifungal activities.Pharmaceutics2024168106510.3390/pharmaceutics16081065 39204411
    [Google Scholar]
  62. JainV.K. JainK. PopliH. Conjugates of amphotericin B to resolve challenges associated with its delivery.Expert Opin. Drug Deliv.202421218721010.1080/17425247.2024.2308073 38243810
    [Google Scholar]
  63. GuoH. MiP. Polymer–drug and polymer–protein conjugated nanocarriers: Design, drug delivery, imaging, therapy, and clinical applications.Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.2024164198810.1002/wnan.1988 39109479
    [Google Scholar]
  64. DashR. YadavM. BiswalJ. ChandraA. GoelV.K. SharmaT. PrustyS.K. MohapatraS. Modeling of chitosan modified PLGA atorvastatin-curcumin conjugate (AT-CU) nanoparticles, overcoming the barriers associated with PLGA: An approach for better management of atherosclerosis.Int. J. Pharm.202364012300910.1016/j.ijpharm.2023.123009 37142139
    [Google Scholar]
  65. JunyaprasertV.B. ThummaratiP. Innovative design of targeted nanoparticles: Polymer–drug conjugates for enhanced cancer therapy.Pharmaceutics2023159221610.3390/pharmaceutics15092216 37765185
    [Google Scholar]
  66. PérezY. UristaC. MartínezJ. NavaM. RodríguezF. Functionalized polymers for enhance oral bioavailability of sensitive molecules.Polymers20168621410.3390/polym8060214 30979310
    [Google Scholar]
  67. YoshieK. IshiharaK. Improvement of oral absorption of poorly water-soluble drugs by solid dispersions with amphiphilic phospholipid polymer.J. Pharm. Sci.2022111113141314810.1016/j.xphs.2022.08.009 36028136
    [Google Scholar]
  68. SantV.P. SmithD. LerouxJ.C. Enhancement of oral bioavailability of poorly water-soluble drugs by poly(ethylene glycol)-block-poly(alkyl acrylate-co-methacrylic acid) self-assemblies.J. Control. Release2005104228930010.1016/j.jconrel.2005.02.010 15907580
    [Google Scholar]
  69. ChenW. ShahL.A. YuanL. SiddiqM. HuJ. YangD. Polymer–paclitaxel conjugates based on disulfide linkers for controlled drug release.RSC Advances20155107559756610.1039/C4RA12856G
    [Google Scholar]
  70. MinT. YeH. ZhangP. LiuJ. ZhangC. ShenW. WangW. ShenL. Water-soluble poly(ethylene glycol) prodrug of pemetrexed: Synthesis, characterization, and preliminary cytotoxicity.J. Appl. Polym. Sci.2009111144445110.1002/app.29047
    [Google Scholar]
  71. SenanayakeT.H. LuY. BohlingA. RajaS. BandH. VinogradovS.V. Encapsulation of poorly soluble drugs in polymer-drug conjugates: Effect of dual-drug nanoformulations on cancer therapy.Pharm. Res.20143161605161510.1007/s11095‑013‑1265‑3 24452808
    [Google Scholar]
  72. MahmoodS. AlmurisiS.H. AL-Japairai, K.; Hilles, A.R.; Alelwani, W.; Bannunah, A.M.; Alshammari, F.; Alheibshy, F. Ibuprofen-loaded chitosan–lipid nanoconjugate hydrogel with gum arabic: Green synthesis, characterisation, in vitro kinetics mechanistic release study and PGE2 production test.Gels20217425410.3390/gels7040254 34940313
    [Google Scholar]
  73. BevacquaE. CurcioM. SalettaF. VittorioO. CirilloG. TucciP. Dextran-curcumin nanosystems inhibit cell growth and migration regulating the epithelial to mesenchymal transition in prostate cancer cells.Int. J. Mol. Sci.20212213701310.3390/ijms22137013 34209825
    [Google Scholar]
  74. SandalP. KumariL. PatelP. SinghA. SinghD. GuptaG.D. KurmiB.D. Doxorubicin conjugates: An efficient approach for enhanced therapeutic efficacy with reduced side effects.Assay Drug Dev. Technol.202321413715610.1089/adt.2022.102 37083490
    [Google Scholar]
  75. AlayoubiO. PoyrazY. HassanG. GülS.B. ÇalhanN. Mert ŞahinN.M. GautamM. KutluA. Özuğur UysalB. AktenE.D. PekcanÖ. Hydrogels from protein–polymer conjugates: A pathway to next-generation biomaterials.Gels20251129610.3390/gels11020096 39996639
    [Google Scholar]
  76. LiJ. ZhuZ. XueY. DownesA. Analysis of drug molecules in living cells.Crit. Rev. Anal. Chem.202511610.1080/10408347.2025.2453431 39854220
    [Google Scholar]
/content/journals/mrmc/10.2174/0113895575399202250904091749
Loading
/content/journals/mrmc/10.2174/0113895575399202250904091749
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test