Application of Cyclodextrin for Cancer Immunotherapy.

Tumor immunotherapy, compared with other treatment strategies, has the notable advantage of a long-term therapeutic effect for preventing metastasis and the recurrence of tumors, thus holding great potential for the future of advanced tumor therapy. However, due to the poor water solubility of immune modulators and immune escape properties of tumor cells, the treatment efficiency of immunotherapy is usually significantly reduced. Cyclodextrin (CD) has been repeatedly highlighted to be probably one of the most investigated building units for cancer therapy due to its elegant integration of an internal hydrophobic hollow cavity and an external hydrophilic outer surface. The application of CD for immunotherapy provides new opportunities for overcoming the aforementioned obstacles. However, there are few published reviews, to our knowledge, summarizing the use of CD for cancer immunotherapy. For this purpose, this paper provides a comprehensive summary on the application of CD for immunotherapy with an emphasis on the role, function, and reported strategies of CD in mediating immunotherapy. This review summarizes the research progress made in using CD for tumor immunotherapy, which will facilitate the generation of various CD-based immunotherapeutic delivery systems with superior anticancer efficacy.

Delivery of melarsoprol using folate-targeted PEGylated cyclodextrin-based nanoparticles for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and has become one of the most lethal malignancies in the world. Although chemotherapy remains a cornerstone of cancer therapy, the number of chemotherapeutic drugs approved for HCC is low, and emerging therapeutics are needed. Melarsoprol (MEL) is an arsenic-containing drug, and has been applied in the treatment of human African trypanosomiasis at the late stage. In this study, the potential of MEL for HCC therapy was investigated for the first time using in vitro and in vivo experimental approaches. A folate-targeted polyethylene glycol-modified amphiphilic cyclodextrin nanoparticle was developed for safe, efficient and specific delivery of MEL. Consequently, the targeted nanoformulation achieved cell-specific uptake, cytotoxicity, apoptosis and migration inhibition in HCC cells. Furthermore, the targeted nanoformulation significantly prolonged the survival of mice with orthotopic tumor, without causing toxic signs. This study indicates the potential of the targeted nanoformulation as an emerging chemotherapy option for treating HCC.

A different approach to immunochemotherapy for colon Cancer: Development of nanoplexes of cyclodextrins and Interleukin-2 loaded with 5-FU.

Immune system deficiencies are crucial in the progression of cancer, predominantly because immune cells are not stimulated by cytokines to eradicate cancer cells. Immunochemotherapy is currently considered an innovative approach that creates pathways in cancer treatment, sometimes also aiding in the efficacy of chemotherapeutics. The aim of this study was to prepare a cyclodextrin (CD) nanoplex based on charge interaction to deliver the anticancer drug 5-fluorouracil (5-FU) and Interleukin-2 (IL-2), thereby forming a nanoscale drug delivery system aimed at chemo-immunotherapy for colorectal cancers. The CD:IL-2 nanoplexes were obtained with a particle size below 100 nm and a cationic surface charge based on the extent of charge interaction of the cationic CD polymer with negatively charged IL-2. The loading capacity of CD nanoplexes was 40% for 5-FU and 99.8% for IL-2. Nanoplexes maintained physical stability in terms of particle size and zeta potential in aqueous solution for 1 week at + 4 °C. Moreover, the structural integrity of IL-2 loaded into CD nanoplexes was confirmed by SDS-PAGE analysis. The cumulative release rates of both 5-FU and IL-2 were found to be more than 80% in simulated biological fluids in 12 h. Cell culture studies demonstrate that CD polymers are safe on healthy L929 mouse fibroblast cells. Drug-loaded CD nanoplexes were determined to have a higher anticancer effect than free drug solution against CT26 mouse colon carcinoma cells. In addition, intestinal permeability studies supported the conclusion that CD nanoplexes could be promising candidates for oral chemotherapy as well. In conclusion, effective cancer therapy utilizing the absorptive/cellular uptake effect of CDs, the synergic effect and co-transport of chemotherapeutic drugs and immunotherapeutic molecules is a promising approach. Furthermore, the transport of IL-2 with this nano-sized system can reduce or avoid its toxicity problem in the clinic.

Highly effective gene delivery based on cyclodextrin multivalent assembly in target cancer cells.

Nucleic acid condensation and controlled release remain significant challenges of gene therapy in the fields of chemical biology and nanotechnology. In this work, we have reported a polysaccharide supramolecular assembly constructed using upconversion nanoparticles encapsulated by ß-cyclodextrin-grafted hyaluronic acid (HACD-UCNPs) and spermine modified with arylazopyrazoles (AAPS). Through UV-Vis spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), gel electrophoresis, confocal laser imaging and combination experiments, such an assembly can achieve not only nucleic acid condensation but also targeted cells delivery and controlled release. Furthermore, we investigated the ability of the system to deliver siRNA under hypoxic conditions, and the subsequent NIR irradiation regulation achieved the two-step release of RNA, obtaining the best effect. This strategy provides a new approach for nucleic acid condensation and targeted delivery, which may bring broad potential in gene therapy.

γ-Cyclodextrin-based polypseudorotaxane hydrogels for ophthalmic delivery of flurbiprofen to treat anterior uveitis.

Anterior uveitis is a sight-threatening inflammation inside the eyes. Conventional eye drops for anti-inflammatory therapy need to be administered frequently owing to the rapid elimination and corneal barrier. To address these issues, polypseudorotaxane hydrogels were developed by mixing Soluplus micelles (99.4 nm) and cyclodextrins solution. The optimized hydrogels exhibited shear-thinning and sustained release properties. The hydrogels exhibited higher transcorneal permeability coefficient (Papp, 1.84 folds) than that of drug solutions. Moreover, animal study indicated that the hydrogels significantly increased the precorneal retention (AUC, 21.2 folds) and intraocular bioavailability of flurbiprofen (AUCAqueous humor, 17.8 folds) in comparison with drug solutions. Importantly, the hydrogels obviously boosted anti-inflammatory efficacy in rabbit model of endotoxin-induced uveitis at a reduced administration frequency. Additionally, the safety of hydrogels was confirmed by cytotoxicity and ocular irritation studies. In all, the present study demonstrates a friendly non-invasive strategy based on γ-CD-based polypseudorotaxane hydrogels for ocular drug delivery.

Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemotherapy.

In the few last years, nanosystems have emerged as a potential therapeutic approach to improve the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticles have been widely investigated as drug delivery systems. The covalent functionalization of CyD polymer nanoparticles with targeting molecules can improve the therapeutic potential of this family of nanosystems. In this study, we investigated cross-linked γ- and ß-cyclodextrin polymers as carriers for doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized γ-CyD polymer bearing COOH functionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptors of cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursor polymer with COOH functionalities and its derivatives in A549 (lung, carcinoma) and HepG2 (liver, carcinoma) cell lines. We found that CyD polymers can significantly improve the antiproliferative activity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced in both cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did not show any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showed that the higher antiproliferative activity of complexes correlates with the higher accumulation of Dox inside the cells. The results show that CyD polymers could be used as carriers for repositioning classical anticancer drugs such as Dox or Oxa to increase their antitumor activity.

Sequential Phase II clinical trials evaluating CRLX101 as monotherapy and in combination with bevacizumab in recurrent ovarian cancer.

BACKGROUND: Topoisomerase-1 inhibitors are an important class of cytotoxics associated with toxicity that limits their use. CRLX101 is a novel cyclodextrin-containing polymer conjugate of camptothecin (CPT) that self-assembles into nanoparticles to deliver sustained levels of active CPT into cancer cells while substantially reducing systemic exposure. METHODS: We conducted sequential phase II, open label, single arm clinical trials to evaluate CRLX101 as a single agent (n = 29) and with bevacizumab (Bev) (n = 34). Patients (pts) had measurable recurrent epithelial ovarian, tubal or primary peritoneal cancer, that could be platinum refractory, resistant or sensitive. Cohort A (Single agent CRLX101) allowed up to 3 prior chemotherapy regimens, but no prior topo-1 inhibitors. Pts received CRLX101 15 mg/m2 IV every 14 days Q28 with response evaluation every 2 cycles. Cohort B also received Bev 10 mg/kg D1,15 Q28, and included only platinum resistant disease with up to 2 prior lines, and more rigorous eligibility criteria. RESULTS: CRLX101 was well tolerated other than nausea, fatigue and anemia. 29 pts. received a median of 3 (1-16) cycles with a clinical benefit rate (CBR) of 68% and overall response rate (ORR) of 11%. With the addition of Bev in Cohort B (n = 34), the CBR was increased to 95% and the ORR to 18%. PFS was 4.5 months (0.9 to 15.9 months) in Cohort A and 6.5 months (2.8 to 14.4 months) in Cohort B. Bev increased the incidence of hypertension and qualitatively increased bladder toxicities, but without SAEs. CONCLUSIONS: CRLX101 meets the clinical need for an effective and tolerable topoisomerase I inhibitor and can be safely combined with bevacizumab.

Antitumor Activity of NLG207 (Formerly CRLX101) in Combination with Enzalutamide in Preclinical Prostate Cancer Models.

Effective treatments for patients with metastatic castration-resistant prostate cancer following disease progression on enzalutamide are currently an unmet clinical need. Simultaneous inhibition of the hypoxia-inducible factor (HIF)-1α and androgen receptor (AR) pathways has been previously shown to overcome enzalutamide resistance in vitro Combination treatment with NLG207, a nanoparticle-drug conjugate of camptothecin and inhibitor of HIF-1α, and enzalutamide was evaluated in preclinical prostate cancer models of enzalutamide resistance. The effect of NLG207 and enzalutamide on average tumor volume and tumor re-growth after 3 weeks of treatment was evaluated in vivo using the subcutaneous 22Rv1 xenograft and castrated subcutaneous VCaP xenograft models. Correlative assessments of antitumor activity were evaluated in vitro using cell proliferation and qPCR assays. NLG207 8 mg/kg alone and in combination with enzalutamide reduced average tumor volume by 93% after 3 weeks of treatment (P < 0.05) in comparison with vehicle control in the subcutaneous 22Rv1 xenograft model. Notably, the addition of NLG207 also enhanced the efficacy of enzalutamide alone in the castrated subcutaneous VCaP xenograft model, decreasing the median rate of tumor growth by 51% (P = 0.0001) in comparison with enzalutamide alone. In vitro assessments of cell proliferation and gene expression further demonstrated antitumor activity via AR-HIF-1α crosstalk inhibition. Combination treatment with NLG207 and enzalutamide was shown to be effective in preclinical prostate cancer models of enzalutamide resistance. Clinical investigation of this treatment combination is ongoing (NCT03531827).

Drug-Encapsulated Cyclodextrin Nanosponges.

To date, a number of nanocarriers, either inorganic or organic, have been developed to improve the delivery and therapeutic efficacy of various drugs. Drug delivery systems have attempted to overcome the undesirable pharmacokinetic problems encountered. Among the various nanomaterials that have been designed as potential nanocarriers, cyclodextrin-based polymers are of particular interest in this review.Cyclodextrins (CD) are a class of cyclic glucopyranose oligomers, obtained from starch by enzymatic action, with a characteristic toroidal shape that forms a truncated cone-shaped lipophilic cavity. The main common native cyclodextrins are named α, ß, and γ which comprise six, seven, and eight glucopyranose units, respectively. Cyclodextrins have the capability to include compounds whose size and polarity are compatible with those of their cavity.Cyclodextrin-based cross-linked polymers, often referred to as "cyclodextrin nanosponges" (CDNSs), attract great attention from researchers for solving major bioavailability problems such as inadequate solubility, poor dissolution rate, and limited stability of some agents, as well as increasing their effectiveness and decreasing unwanted side effects.Registered patents about this novel system in various fields, different pharmaceutical applications, and classes of drugs encapsulated by CDNSs are detailed. The features outlined make CDNSs a promising platform for the development of innovative and advanced delivery systems.

Measurement of NLG207 (formerly CRLX101) nanoparticle-bound and released camptothecin in human plasma.

Camptothecin (CPT), a potent inhibitor of topoisomerase I and HIF-1α, failed to demonstrate utility as an anti-cancer agent in early clinical trial investigations, primarily due to limited clinical activity and significant toxicity attributable to unfavorable physicochemical properties (e.g. low plasma solubility, pH-labile lactone ring). NLG207 (formerly CRLX101), a nanoparticle-drug conjugate (NDC) of CPT designed to optimize plasma pharmacokinetics and facilitate drug delivery to tumors, is included as part of combination treatment in two Phase II clinical trials ongoing at the National Cancer Institute (NCT02769962 and NCT03531827). To better understand the potential for drug-drug interactions and to correlate drug exposure to clinical outcomes and pharmacodynamic biomarkers, a robust analytical method was developed to measure CPT in human plasma. Two sample processing methods were developed to quantify both NDC-bound CPT and free CPT, primarily via alteration of pH conditions. A solid-phase extraction recovered >79 % of CPT prior to quantitative analysis by ultra HPLC-MS/MS. Dynamic calibration ranges of 10 to 10,000 ng/mL and 1 to 1000 ng/mL for total and free CPT, respectively were utilized to capture clinical ranges. NLG207 NDCs demonstrated significant rates of CPT release in human plasma at room temperature after 2 h but were shown to be stable at 4 °C for 24 h and through 4 freeze/thaw cycles. This assay was used to quantitate CPT plasma concentrations in clinical samples to confirm clinical utility following NLG207 treatment in subjects with advanced prostate cancer.

Porphyrinoid-Cyclodextrin Assemblies in Biomedical Research: An Update.

Porphyrinoids, well-known cofactors in fundamental processes of life, have stimulated interest as synthetic models of natural systems and integral components of photodynamic therapy, but their utilization is compromised by self-aggregation in aqueous media. The capacity of cyclodextrins to include hydrophobic molecules in their cavity provides porphyrinoids with a protective environment against oxidation and the ability to disperse efficiently in biological fluids. Moreover, engineered cyclodextrin-porphyrinoid assemblies enhance the photodynamic abilities of porphyrinoids, can carry chemotherapeutics for synergistic modalities, and can be enriched with functions including cell recognition, tissue penetration, and imaging. This Perspective includes synthetic porphyrinoid-cyclodextrin models of proteins participating in fundamental processes, such as enzymatic catalysis, respiration, and electron transfer. In addition, since porphyrinoid-cyclodextrin systems comprise third generation photosensitizers, recent developments for their utilization in photomedicine, that is, multimodal therapy for cancer (e.g., PDT, PTT) and antimicrobial treatment, and eventually in biocompatible therapeutic or diagnostic platforms for next-generation nanomedicine and theranostics are discussed.

NLG919/cyclodextrin complexation and anti-cancer therapeutic benefit as a potential immunotherapy in combination with paclitaxel.

NLG919 is an effective small molecule inhibitor of indoleamine 2, 3-dioxygenase-1 (IDO-1) in anti-tumour immunotherapy, but the poor aqueous solubility limits its application for effective intravenous dosing. In this study a cyclodextrin (CD) complexation strategy has been systematically evaluated to achieve a simple and feasible method to prepare an NLG919 injectable formulation. From a series of CDs, HP-ß-CD proved to be the most conducive for NLG919 solubilization (approx 800-fold increase). Characterization studies using DSC, 1H NMR, XRPD and molecular simulation demonstrated that the NLG919/HP-ß-CD loading mechanism involved an increasing pH-dependent binding affinity. Importantly cell-based studies in vitro and anti-tumour activity in vivo demonstrated that the pharmacological activity of NLG919 as an IDO-1 inhibitor was not influenced by HP-ß-CD complexation. Furthermore, the combination of NLG919/HP-ß-CD with paclitaxel (PTX) significantly improved anti-tumour chemotherapy compared to PTX alone. In summary, NLG919/HP-ß-CD is shown to highly enhance the aqueous solubility of NLG919 with activity unaffected, greatly facilitating the intravenous use of this small molecule immunotherapeutic to improve the efficacy of PTX.

Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer.

CRLX101 is a nanoparticle-drug conjugate with a camptothecin payload. We assessed the toxicity and pathologic complete response (pCR) rate of CRLX101 with standard neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. A single-arm study was conducted with a 3 + 3 dose escalation phase Ib followed by phase II at the maximum tolerated dose (MTD). Thirty-two patients were enrolled with 29 (91%) patients having T3/4 and 26 (81%) N1/2 disease. In phase Ib, no patient experienced a dose limiting toxicity (DLT) with every other week dosing, while 1/9 patients experienced a DLT with weekly dosing. The weekly MTD was identified as 15 mg/m2. The most common grade 3-4 toxicity was lymphopenia, with only 1 grade 4 event. pCR was achieved in 6/32 (19%) patients overall and 2/6 (33%) patients at the weekly MTD. CRLX101 at 15 mg/m2 weekly with neoadjuvant CRT is a feasible combination strategy with an excellent toxicity profile. Clinicaltrials.gov registration NCT02010567.

Cyclodextrin-based delivery systems for cancer treatment.

Cyclodextrins, one of safe excipients, are able to form host-guest complexes with fitted molecules given the unique nature imparted by their structure in result of a number of pharmaceutical applications. On the other hand, targeted or responsive materials are appealing therapeutic platforms for the development of next-generation precision medications. Meanwhile, cyclodextrin-based polymers or assemblies can condense DNA and RNA in result to be used as genetic therapeutic agents. Armed with a better understanding of various pharmaceutical mechanisms, especially for cancer treatment, researchers have made lots of works about cyclodextrin-based drug delivery systems in materials chemistry and pharmaceutical science. This Review highlights recent advances in cyclodextrin-based delivery systems for cancer treatment capable of targeting or responding to the physiological environment. Key design principles, challenges and future directions, including clinical translation, of cyclodextrin-based delivery systems are also discussed.

An oxaliplatin(iv) prodrug-based supramolecular self-delivery nanocarrier for targeted colorectal cancer treatment.

A redox-responsive supramolecular nanocarrier was constructed from the self-assembly of spermine modified cyclodextrin and oxaliplatin prodrug. The nanocarrier could preferentially accumulate in polyamine transporter over-expressing HCT116 cells, releasing drugs under a reducing intracellular environment to maximize anticancer treatment.

Use of Cyclodextrins in Anticancer Photodynamic Therapy Treatment.

Photodynamic therapy (PDT) is mainly used to destroy cancerous cells; it combines the action of three components: a photoactivatable molecule or photosensitizer (PS), the light of an appropriate wavelength, and naturally occurring molecular oxygen. After light excitation of the PS, the excited PS then reacts with molecular oxygen to produce reactive oxygen species (ROS), leading to cellular damage. One of the drawbacks of PSs is their lack of solubility in water and body tissue fluids, thereby causing low bioavailability, drug-delivery efficiency, therapeutic efficacy, and ROS production. To improve the water-solubility and/or drug delivery of PSs, using cyclodextrins (CDs) is an interesting strategy. This review describes the in vitro or/and in vivo use of natural and derived CDs to improve antitumoral PDT efficiency in aqueous media. To achieve these goals, three types of binding modes of PSs with CDs are developed: non-covalent CD⁻PS inclusion complexes, covalent CD⁻PS conjugates, and CD⁻PS nanoassemblies. This review is divided into three parts: (1) non-covalent CD-PS inclusion complexes, covalent CD⁻PS conjugates, and CD⁻PS nanoassemblies, (2) incorporating CD⁻PS systems into hybrid nanoparticles (NPs) using up-converting or other types of NPs, and (3) CDs with fullerenes as PSs.

Curcumin as Treatment for Bladder Cancer: A Preclinical Study of Cyclodextrin-Curcumin Complex and BCG as Intravesical Treatment in an Orthotopic Bladder Cancer Rat Model.

OBJECTIVE: To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. METHODS: Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. RESULTS: CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage. CONCLUSIONS: Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.

Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac.

With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α-, ß-, γ-, and HP-ß-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, α-, ß-, γ-, and HP-ß-CD inclusion complexes were prepared and characterized and Diclo-CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion complexes were formed only with ß-, γ-, and HP-ß-CDs. Amphipathic properties for Diclo were recorded and this surfactant-like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo-CDs in solution. Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability to free Diclo were recorded only with Diclo-γ-CD and Diclo-HP-ß-CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo-γ-CD and Diclo-HP-ß-CD demonstrated fast healing without scar formation.

Therapeutic potential of novel formulated forms of curcumin in the treatment of breast cancer by the targeting of cellular and physiological dysregulated pathways.

Breast cancer is among the most important causes of cancer related death in women. There is a need for novel agents for targeting key signaling pathways to either improve the efficacy of the current therapy, or reduce toxicity. There is some evidence that curcumin may have antitumor activity in breast cancer. Several clinical trials have investigated its activity in patients with breast cancer, including a recent trial in breast cancer patients receiving radiotherapy, in whom it was shown that curcumin reduced the severity of radiation dermatitis, although it is associated with low bioavailability. Several approaches have been developed to increase its absorption rate (e.g., nano crystals, liposomes, polymers, and micelles) and co-delivery of curcumin with adjuvants as well as different conjugation to enhance its bioavailability. In particular, micro-emulsions is an option for transdermal curcumin delivery, which has been reported to increase its absorption. Lipid-based nano-micelles is another approach to enhance curcumin absorption via gastrointestinal tract, while polymer-based nano-formulations (e.g., poly D, L-lactic-co-glycolic [PLGA]) allows the release of curcumin at a sustained level. This review summarizes the current data of the therapeutic potential of novel formulations of curcumin with particular emphasis on recent preclinical and clinical studies in the treatment of breast cancer.

Cyclodextrin-containing hydrogels as an intraocular lens for sustained drug release.

To improve the efficacy of anti-inflammatory factors in patients who undergo cataract surgery, poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (p(HEMA-co-MMA)) hydrogels containing ß-cyclodextrin (ß-CD) (pHEMA/MMA/ß-CD) were designed and prepared as intraocular lens (IOLs) biomaterials that could be loaded with and achieve the sustained release of dexamethasone. A series of pHEMA/MMA/ß-CD copolymers containing different ratios of ß-CD (range, 2.77 to 10.24 wt.%) were obtained using thermal polymerization. The polymers had high transmittance at visible wavelengths and good biocompatibility with mouse connective tissue fibroblasts. Drug loading and release studies demonstrated that introducing ß-CD into hydrogels increased loading efficiency and achieved the sustained release of the drug. Administering ß-CD via hydrogels increased the equilibrium swelling ratio, elastic modulus and tensile strength. In addition, ß-CD increased the hydrophilicity of the hydrogels, resulting in a lower water contact angle and higher cellular adhesion to the hydrogels. In summary, pHEMA/MMA/ß-CD hydrogels show great potential as IOL biomaterials that are capable of maintaining the sustained release of anti-inflammatory drugs after cataract surgery.