Combined microneedling for the treatment of androgenetic alopecia / 中华皮肤科杂志

Microneedling is a simple, safe, effective, minimally invasive, and economical treatment technique with a wide range of indications. Studies in China and other countries have showed that microneedling plays a role in the treatment of androgenetic alopecia. Compared with traditional therapies, combined microneedling has better therapeutic efficacy, shorter treatment course and a better safety profile. This review summarizes the therapeutic efficacy, mechanisms of action and safety of combined microneedling, and describes prospective trends in the treatment of androgenetic alopecia with combined microneedling based on recent relevant Chinese and international literature.

Efficacy of gold microneedle combined with tranexamic acid transdermal administration for treatment of post-inflammatory hyperpigmentation from acne vulgaris / 中华医学美学美容杂志

Objective:To evaluate the efficacy of gold microneedle combined with tranexamic acid transdermal administration for the treatment of post-inflammatory hyperpigmentation caused by acne vulgaris.Methods:From January 2022 to October 2022, 36 patients with post-inflammatory hyperpigmentation of facial acne who went to the Laser Medical Center, Air Force Medical Center were treated, including 10 males and 26 females, with 21-42 (28.3±4.8) years of age. The patients were divided into observation group and control group, with 18 cases in each group. The observation group was treated with gold microneedle combined with transdermal administration of tranexamic acid, the control group with 0.5 mm microneedles combined with transdermal administration of tranexamic acid. Both groups were treated for 2 times with an interval of 2 months. The total effective rate, post acne hyperpigmentation index (PAHPI), UV spots, brown spots, pores, skin texture, and adverse reaction were evaluated at 4 weeks after the last treatment.Results:Clinical observation was completed in all 36 patients. In the observation group, 17 cases were effective, accounting for 94.4%, and in the control group, 11 cases were effective, accounting for 61.1%, The curative effect of the observation group was better than that of the control group, and the difference between the two groups was statistically significant ( P<0.05). The differences in PAHPI score, UV spots, brown spots, pores, and skin texture between the two groups were also statistically significant ( t=3.10, 2.52, 2.71, 2.43 and 3.54; P=0.004, 0.017, 0.001, 0.021 and 0.001). The patiens in both groups had different degrees of burning sensation, erythema, edema. dryness and other symptoms after treatment, which were relieved 3 days after treatment without special treatmet. Conclusions:Gold microneedle plus transdermal administrationof tranexamic acid is a safe and effective method for the treatment of post-inflammatory pigmentation caused by acne vulgaris.

Research progress of exosome microneedle drug delivery system / 中国药房

Microneedles can penetrate the skin barrier to deliver drugs without touching the nociceptive nerves， to effectively increase the efficiency of transdermal drug delivery and improve patient compliance. Exosomes have multiple physiological functions and good biocompatibility， and are natural nanoscale drug carriers. This paper reviews the pathways and advantages of exosomes combined with microneedles for the treatment of diseases， and describes the current research status of exosome microneedle drug delivery system in various diseases. Exosome microneedles can be divided into two categories： （1） exosomes as therapeutic agents， their unique physiological origin can effectively avoid the toxicity and immunogenicity of conventional drugs and other problems； combined with microneedles directly in the specific medication site can greatly improve the metabolic consumption of oral drug delivery and patient compliance of injection drug delivery. （2） Exosomes as drug carriers， their natural vesicle structure and endogenous characteristics can protect the metabolism of foreign drugs in the body and enhance the targeting； combined with microneedles can effectively solve the problem of transdermal delivery of drugs with high efficacy but poor stability. Exosome microneedle drug delivery system is still in the laboratory stage， but it has shown great development prospects in repairing spinal cord injury， promoting diabetic ulcer wound healing， germinating， intervening myocardial infraction， relieving chronic pain and other diseases.

Actively separated microneedle patch for sustained-release of growth hormone to treat growth hormone deficiency

Growth hormone deficiency (GHD) has become a serious healthcare burden, and presents a huge impact on the physical and mental health of patients. Here, we developed an actively separated microneedle patch (PAA/NaHCO3-Silk MN) based on silk protein for sustained release of recombinant human growth hormone (rhGH). Silk protein, as a friendly carrier material for proteins, could be constructed in mild full-water conditions and ensure the activity of rhGH. After manually pressing PAA/NaHCO3-Silk MN patch to skin for 1 min, active separation is achieved by absorbing the interstitial fluid (ISF) to trigger HCO3 ‒ in the active backing layer to produce carbon dioxide gas (CO2). In rats, the MN patch could maintain the sustained release of rhGH for more than 7 days, and produce similar effects as daily subcutaneous (S.C.) injections of rhGH in promoting height and weight with well tolerated. Moreover, the PAA/NaHCO3-Silk MN patch with the potential of painless self-administration, does not require cold chain transportation and storage possess great economic benefits. Overall, the PAA/NaHCO3-Silk MN patch can significantly improve patient compliance and increase the availability of drugs, meet current unmet clinical needs, improve clinical treatment effects of GHD patients.

Application of microneedle-assisted percutaneous drug delivery system in treatment of rheumatoid arthritis:a review / 中国中药杂志

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.

Comparative study on efficacy and safety of single microneedle radiofrequency versus photodynamic therapy in the treatment of inflammatory lesions of moderate to severe facial acne vulgaris / 中华皮肤科杂志

Objective:To compare the clinical efficacy and safety of single microneedle radiofrequency versus photodynamic therapy in the treatment of inflammatory lesions of moderate and severe facial acne vulgaris.Methods:Sixty patients with moderate to severe facial acne vulgaris were retrospectively collected from Guangzhou Institute of Dermatology between December 2021 and July 2022, including 30 patients who had received single microneedle radiofrequency treatment, and 30 patients who had received photodynamic therapy. There were no significant differences in the age, gender distribution, and severity of acne between the two groups (all P > 0.05). The patients in the microneedle radiofrequency group were treated with single microneedle radiofrequency once every 4 weeks for 2 sessions; those in the photodynamic therapy group received aminolevulinic acid-based photodynamic therapy once every 2 weeks for 3 sessions; patients in both groups were still treated with oral doxycycline for 8 weeks. After 8-week treatment, the efficacy, pain severity and incidence of adverse reactions were compared between the two groups. Statistical analysis was carried out by using chi-square test, two independent samples t-test and Mann-Whitney U test. Results:After 8-week treatment, there was no significant difference in the response rate between the microneedle radiofrequency group (93.33%, 28/30) and photodynamic therapy group (86.67%, 25/30; χ2 = 0.74, P = 0.389). No significant difference was observed in the pain severity score between the microneedle radiofrequency group (4.80 ± 2.08) and photodynamic therapy group (4.13 ± 1.86, t = 1.32, P = 0.194), and there was also no significant difference in the pain degree between the two groups ( Z = -1.13, P = 0.260). In the microneedle radiofrequency group, burning sensation occurred in 3 cases (10.00%), swelling and pain in 4 (13.33%), erythema in 2 (6.67%), and dryness and desquamation in 2 (6.67%), and no reactive acne or hyperpigmentation was observed; in the photodynamic therapy group, burning sensation occurred in 10 cases (33.33%), swelling and pain in 9 (30.00%), erythema in 8 (26.67%), reactive acne in 11 (36.67%), hyperpigmentation in 2 (6.67%), and dryness and desquamation in 11 (36.67%). Compared with the photodynamic therapy group, the microneedle radiofrequency group showed significantly decreased incidence rates of burning sensation, erythema, reactive acne, and dryness and desquamation ( χ2 = 4.81, 4.32, 13.47, 7.95, respectively, all P < 0.05) ; there was no significant difference in the incidence rates of swelling and pain as well as hyperpigmentation between the two groups ( χ2 = 2.46, 2.07, respectively, both P > 0.05) . Conclusion:Single microneedle radiofrequency showed marked efficacy equivalent to that of photodynamic therapy in the treatment of moderate to severe facial acne vulgaris, but higher safety, providing more clinical treatment options for moderate to severe facial acne vulgaris.

Comparison of golden microneedle and subcutaneous apocrine gland excision in treatment of axillary osmidrosis / 中华医学美学美容杂志

Objective:To investigate the effect of gold microneedle and subcutaneous apocrine excision in the treatment of bromidrosis and the occurrence of postoperative complications.Methods:From July 2019 to November 2020, 42 patients (13 males and 29 females; 16-47 years old, average 23 years old) were treated with plastic surgery in the First Affiliated Hospital of Xinjiang Medical University, 20 patients received gold microneedle treatment, and 22 patients received minimally invasive surgery (subcutaneous apocrine excision surgery). The patients were followed up for 3-6 months after operation, and the severity of preoperative bromidrosis, postoperative curative effect and occurrence of postoperative complications were compared between the two groups.Results:Eighteen cases were effective in the gold microneedle group, accounting for 90%; 22 cases were effective in the minimally invasive surgery group, accounting for 100%; the difference between the two groups was statistically significant ( P<0.05). There was a negative correlation between the grade of bromidrosis before operation and the curative effect after operation in the gold microneedle group, and the correlation coefficient was not statistically significant in the minimally invasive operation group ( P>0.05). Complications occurred in 4 cases in the gold microneedle group, accounting for 20.0%; 10 cases presented with complications in the minimally invasive surgery group, accounting for 45.5%; the difference was statistically significant ( P<0.05). Conclusions:The therapeutic effect of gold microneedle is lower than that of minimally invasive surgery, and the higher the degree of bromidrosis, the worse the curative effect. The postoperative complication rate of gold microneedle treatment for bromidrosis is lower than that of minimally invasive surgery.

Progress on drug delivery of iontophoresis / 药学实践与服务

Iontophoresis is a non-invasive physical permeation technology, which has been widely applied in transdermal and transmucosal administration. Compared with other permeation technologies, iontophoresis have the advantages of high efficacy, high patient compliance and controllable delivery dose. With the development of microneedles and nano-carrier technology, the combination of iontophoresis and other penetration promotion technologies has gradually become a research hotspot. The penetration mechanism and influencing factors of iontophoresis, and the study on the combination of iontophoresis with hydrogel, microneedles or nano-carrier were reviewed in this paper.

Microneedle-based interstitial fluid extraction for drug analysis:Advances,challenges,and prospects / 药物分析学报

Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alterna-tives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.

Effect of microneedle radiofrequency combined with supramolecular salicylic acid on facial photoaging / 中华医学美学美容杂志

Objective:To explore the efficacy and safety of microneedle radiofrequency combined with supramolecular salicylic acid in improving facial photoaging.Methods:Thirty patients treated for facial photoaging were randomly divided into the combined treatment group and the microneedle radiofrequency group. All patients were female, aged between 30 and 50 years, with an average age of (39.4±4.1) years. The combined treatment group was treated with microneedle radiofrequency combined with supramolecular salicylic acid, and the Microneedle radiofrequency group was treated with microneedle radiofrequency alone. The patients were followed up 3 days, 7 days, 14 days, 28 days and 3 months after treatment. The results of VISIA, skin physiology and patients' satisfaction were used to compare the two groups of patients after treatment.Results:After 3 months of treatment, the skin pores (11.98±2.14 vs. 15.54±1.52), brown spots (12.40±1.85 vs. 15.84±1.42), ultraviolet spots (6.74±0.87 vs. 11.20±1.70), skin physiological status (transepidermal water loss): 11.84±1.80 vs 13.09±1.96 g/(h·m) 2, stratum corneum water content: 84.91±2.86 % vs 80.29±3.58 %, melanin index: 110.07±15.02 vs. 122.30±9.97, erythema index: 220.43±19.69 vs. 236.30±16.55), elasticity (75.98±3.94 vs. 69.89±3.58), epidermal thickness (1401.33±178.43 vs. 1217.13±139.77), skin color improvement (effective rate 86.7% vs. 40.0%) and patients' satisfaction (total satisfaction was 93.3% vs 67.0%) in the combined treatment group were significantly superior than those in the microneedle radiofrequency group, and the differences were statistically significant ( P<0.05). The reaction of moderate and severe erythema (the incidence rate 40.0% vs. 86.7%) and edema (the incidence rate 26.7% vs. 80.0%) in the combined treatment group was also significantly lower than that in the microneedle radiofrequency group ( P<0.05). No adverse pigmentation was reported in both groups after treatment. Conclusions:The combination of microneedle radiofrequency and supramolecular salicylic acid in the treatment of facial photoaging has definite clinical effect and high safety, which is worthy of clinical application.

Purpurolide C-based microneedle promotes macrophage-mediated diabetic wound healing via inhibiting TLR4-MD2 dimerization and MYD88 phosphorylation

Delayed wound healing in diabetes is a global challenge, and the development of related drugs is a clinical problem to be solved. In this study, purpurolide C (PC), a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum, was found to promote diabetic wound healing. To investigate the key regulation targets of PC, in vitro RNA-seq, molecular docking calculations, TLR4-MD2 dimerization SDS-PAGE detection, and surface plasmon resonance (SPR) were performed, indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation. Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing. Furthermore, a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC (PC@MLIP MN) was developed, which overcame the poor water solubility and weak skin permeability of PC, so that successfully punctured the skin and delivered PC to local tissues, and accurately regulated macrophage polarization in diabetic wound management. Overall, PC is an anti-inflammatory small molecule compound with a well-defined structure and dual-target regulation, and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.

Mechanical properties and immunotherapeutic effects of dissolving microneedles with different drug loadings based on hyaluronic acid

Abstract Improving vaccine immunity and reducing antigen usage are major challenges in the clinical application of vaccines. Microneedles have been proven to be painless, minimally invasive, highly efficient, and have good patient compliance. Compared with traditional transdermal drug delivery, it can effectively deliver a large-molecular-weight drug into the skin, resulting in a corresponding immune response. However, few studies have examined the relationship between microneedle loading dose and immune effects. In this study, the hyaluronic acid (HA) conical and pyramidal dissolving microneedles were prepared by the two-step vacuum drying method, respectively. The model drug ovalbumin (OVA) was added to HA to prepare dissolving microneedles with different loading amounts. The mass ratios of HA to OVA were 5:1, 5:3, and 5:5. The mechanical properties of the dissolving microneedles were characterized using nanoindentation and in vitro puncture studies. The immune effects of the matrix and drug content were studied in Sprague-Dawley (SD) rats. Finally, the diffusion behavior of OVA and the binding mode of HA and OVA in the microneedles were simulated using Materials Studio and Autodocking software. The experimental results showed that the conical microneedles exhibited better mechanical properties. When the mass ratio of HA to OVA was 5:3, the immune effect can be improved by 37.01% compared to subcutaneous injection, and achieved a better immune effect with relatively fewer drugs. This conclusion is consistent with molecular simulations. This study provides theoretical and experimental support for the drug loading and efficacy of microneedles with different drug loadings

Advances of microneedle vaccines in transcutaneous immunization / 药学学报

Vaccination is an effective way to reduce the morbidity and mortality of infectious diseases. As a needle-free transcutaneous immunization (NF-TCI) vaccination technology, microneedles (MNs), composed of multiple micro-needles orderly attached to a substrate, can overcome the problems of low immune efficiency, poor compliance and waste of resources that exists in the conventional vaccination by injection, thus becoming a research hotspot in biomedicine. The microneedle vaccine can directly break through the stratum corneum barrier of the skin without touching nerves and blood vessels in the dermis, and effectively delivers the vaccine to the immune cells in the skin tissue to initiate the immune response of the body, thus triggering strong humoral and cellular immune processes. Vaccine delivery via the MNs system possesses the advantages of high safety, satisfying immune effect and practical economy, and shows great prospect in the prevention and treatment of infectious diseases and antineoplastic therapy. This article reviews the development background of MNs in transcutaneous immunization, the types of vaccine delivery, the factors affecting the immune effect, the problems to be solved and development direction in the future.

Clinical efficacy of injection of recombinant humanized type Ⅲ collagen in facial rejuvenation / 中华医学美学美容杂志

Objective:To evaluate the efficacy of recombinant humanized type Ⅲ collagen injected by microneedles in facial rejuvenation.Methods:Twenty-five cases recruited from July to December 2021 were included as the research objects in this study. Recombinant humanized type Ⅲ collagen was injected into the face skin using microneedles. Images were collected before the treatment and 1, 2, and 3 months after the end of the treatment. The VISIA image analysis system was used for comparative analysis. Patient′s satisfaction evaluation and the occurrence of complications after treatment were also recorded.Results:According to results of VISIA, the scores of spots were (32.06±6.92) and (27.59±7.69); red areas were (32.79±11.80) and (27.74±9.49); pores were (17.66±9.79) and (14.60±7.07) and brown spots were (43.61±11.93) and (37.59±16.22) after the treatment were lower than those before treatment, and the results were statistically different ( F=3.442, 4.209, 7.473, 7.113, P<0.05). One month after the end of the of treatment. Patient′s self-satisfaction reached 84% (21 cases); three months after the end of the treatment, the patient′s self-satisfaction reached 80% (20 cases). No serious adverse reactions were occurred. Conclusions:The recombinant humanized type Ⅲ collagen injected by microneedles can be effective and durable for facial rejuvenation and get high patient satisfaction. It has high safety and is worthy of clinical promotion.

Efficacy of microneedle radiofrequency for treatment of moderate acne vulgaris / 中华医学美学美容杂志

Objective:To evaluate the clinical efficacy of microneedle radiofrequency in the treatment of moderate acne vulgaris.Methods:From August 2018 to August 2020, 393 patients (192 males and 201 females, aged 15-38 years) with moderate acne were enrolled in the Department of Dermatology, the First Affiliated Hospital of Shantou University Medical College and Shantou Chaonan Minsheng Hospital, including 201 patients in experimental group and 192 patients in control group. In the experimental group, microneedle radiofrequency therapy was used once every 2 weeks for 3 times in total. The control group adopted the fire needle, once every 2 weeks, a total of 3 times. The efficacy of both groups was evaluated at week 8.Results:A total of 378 patients were actually completed: 196 patients in the experimental group, and 182 patients in the control group. At the eighth week of follow-up, the total effective rate was 81.12% in the experimental group and 70.43% in the control group. The efficacy of the two groups was statistically different (χ 2=4.42, P<0.05). Conclusions:The efficacy of microneedle radiofrequency therapy in the treatment of moderate acne vulgaris is better than that of fire needle, with good tolerance, short recovery period, few adverse reactions and high compliance, which has clinical promotion value.

Enhanced uptake and anti-maturation effect of celastrol-loaded mannosylated liposomes on dendritic cells for psoriasis treatment

Psoriasis is an autoimmune skin disease in which dendritic cells (DCs) trigger the progression of psoriasis by complex interactions with keratinocytes and other immune cells. In the present study, we aimed to load celastrol, an anti-inflammatory ingredient isolated from Chinese herbs, on mannosylated liposomes to enhance DC uptake as well as to induce DC tolerance in an imiquimod-induced psoriasis-like mouse model. Mannose was grafted onto liposomes to target mannose receptors on DCs. The results demonstrated that compared with unmodified liposomes, DCs preferred to take up more fluorescence-labeled mannosylated liposomes. After loading celastrol into mannose-modified liposomes, they effectively inhibited the expression of maturation markers, including CD80, CD86 and MHC-II, on DCs both in vitro and in vivo. Additionally, after intradermal injection with a microneedle, celastrol-loaded mannose-modified liposomes (CEL-MAN-LPs) achieved a superior therapeutic effect compared with free drug and celastrol-loaded unmodified liposomes in the psoriasis mouse model in terms of the psoriasis area and severity index, histology evaluation, spleen weight, and expression of inflammatory cytokines. In conclusion, our results clearly revealed that CEL-MAN-LPs was an effective formulation for psoriasis treatment and suggested that this treatment has the potential to be applied to other inflammatory diseases triggered by activated DCs.

Immune effects of Clostridium difficile toxoid B vaccine formulated with different mucosal adjuvants through microneedle immunization / 中华微生物学和免疫学杂志

Objective:To investigate the immune effects of Clostridium difficile toxoid B (CdtB) vaccine formulated with different mucosal adjuvants through microneedle immunization, and to provide ideas for the prevention and treatment of Clostridium difficile infection. Methods:CdtB vaccine was prepared with purified Clostridium difficile toxin B(TcdB) after formaldehyde detoxification. Female BALB/c mice were immunized with different doses of vaccine alone or in combination with mucosal adjuvants. The titers of specific serum IgG and fecal IgA were detected at 0 d, 7 d, 14 d, 28 d and 42 d after immunization. The protective effects of CdtB vaccine were evaluated by cell neutralization assay and Clostridium difficile challenge infection. Results:(1) With the increase of immune dose, the mice immunized with CdtB vaccine alone by microneedle not only produced better serum specific IgG, but also had higher level of IgA in feces. (2) When the mice were immunized with CdtB vaccine containing LT or CTB adjuvant by microneedle, the trend of serum specific IgG titer in each group increased with the increase of immune dose, especially in the group containing LT adjuvant. There were significant differences in the trend of specific IgA titer in feces between the adjuvant groups and the group without adjuvant, but the adjuvant effect was not obvious. (3) No significant difference in serum IgG titer was observed between the mice immunized with 10 μg CdtB by microneedle or intraperitoneal injection, but microneedle immunization significantly increased fecal IgA level. (4) The neutralization titers of specific antibodies in mouse serum after immunization and the test results of challenge protection in mice confirmed that the use of CdtB vaccine had certain protective effects.Conclusions:CdtB vaccine had better immune effects in mice through microneedle immunization, but the adjuvant effects of LT and CTB were not significant.

Preparation technology of platelet-rich-plasma lysate combined with hyaluronic acid microneedles and wound healing effect / 中国输血杂志

【Objective】 To investigate the application prospect of platelet-rich plasma lysate (PL) microneedles in the treatment of wound healing by optimizing the preparation process and evaluating the activity of platelet growth factor. 【Methods】 Firstly, hyaluronic acid (HA) was used as needle matrix material, and the concentration of HA was preliminarily determined by investigating the fluidity of HA solution, shape of needle, pressure change performance and puncture performance.Combined with the results of HA dissolution in PL, mechanical properties of PL microneedles and skin puncture, the preparation process of platelet-rich plasma lysis microneedles (PLMN) was optimized to investigate the growth factor activity of PLMN and evaluate the effect of PLMN on wound healing in rats. 【Results】 When the concentration of HA was 30 mg/mL, the solution had good fluidity.The HA microneedles could pierce three layers of sealing film, with the puncture rate at 70%, and the solution had good mechanical properties.When HA was dissolved in PL at a concentration of 30 mg/mL at 4℃, the solution had no crystallization and was with good fluidity.The prepared PLMN showed good needle shape and no bending under HD microscope and scanning electron microscope.In vitro transdermal simulation results showed that PLMN could penetrate 4 layers of sealing membrane, and the puncture rate of the first three layers was more than 85%.In vivo lysis experiment showed that PLMNs could be completely dissolved within 10 min after being inserted into the body.Forty minutes later, the micropores left after the insertion of the microneedle were almost closed, without redness, swelling, erythema and other adverse reactions.In vitro and in vivo transdermal experiments showed that clear blue holes were visible after PLMNs penetrated the skin stain, indicating that the microneedles could pierce the skin barrier.Growth factor detection results showed that the content of platelet-derived growth factor (PDGF-BB) and transforming growth factor (TGFβ1) in platelet lysate were (17.67±1.23) ng/mL and (105.95±2.16) ng/mL, respectively.After PLMNs were prepared and stored at room temperature for 1 week, the content of PDGF-BB(ng/mL) and TGFβ1(ng/mL) were 15.48±2.12 and 56.26±1.53, respectively.Compared with PL(vs 17.67±1.23 and 105.95±2.16), the content of PDGF-BB and TGFβ1 decreased, but still maintained the activity of growth factors.The results of wound healing experiment in rats showed that the wound healing rate (%) of PLMN group on the third day was significantly different from that of the control group(52.51±6.15 vs 33.31±3.60, P<0.05). 【Conclusion】 The PLMN prepared in this experiment has good mechanical properties and can successfully pierce the skin cuticle.It can also maintain the activity of growth factors, and has a good effect on wound healing in rats, which provides a new idea for minimally invasive treatment in the field of tissue repair.

Minimally invasive dissolving microneedles for ocular brinzolamide delivery / 药学学报

The permeation and pharmacodynamics of ocular drugs are influenced by the corneal barrier. Here, a hard-soluble drug, brinzolamide, was selected as the model drug and used for preparation of minimally invasive dissolving microneedles. Brinzolamide was dissolved in ethanol and polyvinylpyrrolidone (PVP) K90 was added and dissolved. The mixture solution was casted into the dissolving microneedles mold and dried and brinzolamide dissolving microneedles (BMN) were obtained after demolding. The stereoscopic and scanning electron microscopic images showed that BMN were conical needles with the height of 750 μm, the bottom diameter of 300 μm, and the inter-tip distance of 500 μm. The dissolving microneedles patch was composed of 10×10 arrays with the area of 1 cm2 and the high drug load of 7.3 mg·cm-2. BMN showed a rapid in vitro drug release with 93% accumulative release at 2 h and the high drug corneal permeation amount of 877 ± 105 μg. BMN exhibited the high mechanical strength of 0.32 N/needle, leading to easy rat corneal insertion with the depth of 200 μm. Moreover, BMN were rapidly dissolved in the cornea, and more importantly, the damaged cornea were quickly self-healed within 24 h. Animal experiments were approved by the Ethics Committee of Beijing Institute of Radiation Medicine, Academy of Military Medical and the experiments were conducted in accordance with relevant guidelines and regulations. Ocular minimally invasive dissolving microneedles have the advantages of corneal minimal wounds and rapid healing, high drug loading, and high permeability, favoring the treatment of ocular diseases.

Preparation and characterization of dissolving microneedles with nano-enhanced mechanical properties / 药学学报

In this paper, the effects of the blend of nanoparticles and microneedle matrix materials on the mechanical properties of dissolving microneedles were studied mainly, so as to construct microneedles with excellent mechanical properties. Different kinds of nanoparticles (calcium carbonate, hydroxyapatite, silica), particle sizes (20, 60, 100 nm) and the proportion of prescription (2%, 6%, 10%) were blended with the matrix material [polyvinyl pyrrolidone (PVP), poly(1-vinylpyrrolidone-co-vinyl acetate)(PVP/VA)] to form dissolving microneedles. The effects of nanoparticles on the elastic modulus and hardness of the microneedles were investigated using a nanoindenter. The results showed that the elastic modulus and hardness of PVP microneedles were significantly improved by nano-calcium carbonate (P < 0.001), and the elastic modulus and hardness of PVP/VA microneedles were significantly improved by nano-hydroxyapatite (P < 0.001). When the particle size of hydroxyapatite was 20 nm, the elastic modulus of PVP/VA microneedles was (10.6 ± 1.0) GPa, and the hardness was (0.47 ± 0.06) GPa. As the size of the nanoparticles increases, the mechanical performance of the microneedles decreases. When the mass proportion of nano-hydroxyapatite increased from 2% to 6%, the elastic modulus and hardness of the microneedles were significantly improved (P < 0.001), but the effect of continue increasing the proportion of nanoparticles on the microneedles was not significant. The nano-enhanced PVP/VA dissolving microneedles has no irritant effect on intact skin and has a slight irritation to damaged skin, but they disappear completely after 72 h. Animal experiments have been approved by the Laboratory Animal Welfare and Ethics Committee of Zhejiang University of Technology. Therefore, the nano-enhanced dissolving microneedles has good biological safety. To sum up, it is necessary to select the appropriate kind of nanoparticle, particle size, and prescription ratio when microneedles constructing with a given matrix material, so as to effectively improve its mechanical performance.